Neoplasms
Conditions
Keywords
GSK3174998, Non-small Cell Lung Cancer (NSCLC), OX40, Pembrolizumab, Monoclonal Antibody (mAb), Selected Advanced Solid Tumors
Brief summary
This is a first time in human (FTIH), open-label, non-randomized, multicenter study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary clinical activity of GSK3174998 administered intravenously to participants with selected advanced or recurrent solid tumors. This dose-escalation study will assess the safety, activity of GSK3174998 as monotherapy (Part 1), in combination with pembrolizumab (Part 2), and potentially in combination with additional therapies. The study will be conducted in 2 parts, each part consisting of starting with a dose-escalation phase followed by a cohort expansion phase. GSK3174998 will first be evaluated as monotherapy in escalating doses. Once a dose of GSK3174998 has been identified that is both tolerable and demonstrates pharmacodynamic activity, enrollment of Part 2 may begin. In Part 2, escalating doses of GSK3174998 will be evaluated with fixed doses of pembrolizumab. The maximum duration of treatment with GSK3174998 and pembrolizumab will be approximately 2 years or 35 cycles, whichever comes first. The follow-up period for safety assessments will be a minimum of 3 months from the date of the last dose. The post-treatment follow-up period will include disease assessments every 12 weeks until documented progressive disease (PD). Approximately 141 participants with selected advanced or recurrent solid tumors will be enrolled.
Interventions
DRUGGSK3174998
Lyophilized powder 40 mg reconstituted to get a dose range of 0.003 to \<=10 mg/kg to be given as IV infusion for 30 minutes (min), Q3W
DRUGPembrolizumab
Pembrolizumab as 100 mg/4 milliliter (mL) solution (dose: 200 mg) to be given as IV infusion for 30 min, Q3W
Sponsors
Merck Sharp & Dohme LLC
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provide signed, written informed consent. * Male and female participants, age \>=18 years (at the time consent is obtained). * Histological documentation of locally advanced, recurrent or metastatic solid malignancy that has progressed after standard therapy appropriate for the specific tumor type, or for which standard therapy has proven to be ineffective, intolerable, or is considered inappropriate. Participants should not have received more than 5 prior lines of therapy for advanced disease including both standards of care and investigational therapies. Participants whose cancers harbor molecular alterations for which targeted therapy is standard of care should have received health authority approved appropriate targeted therapy for their tumor types before enrollment. * Participants with the following solid tumors are eligible for screening: Non-small cell lung cancer (NSCLC), Squamous cell carcinoma of the head and neck (SCCHN), Renal cell carcinoma (RCC), melanoma, bladder, Soft Tissue Sarcoma (STS), Triple-negative breast cancer (TNBC), and Colorectal carcinoma displaying high microsatellite instability (MSI CRC). In Part 2B (Cohort Expansion), specific subgroups of the above solid tumors will be studied. These subgroups may be defined by specific lines of treatment, types of prior treatment, histological subtypes, and may be enriched for selected biomarkers or participant characteristics. Populations to be studied in Amendment 3 include but are not limited to the following. Enrolment of additional populations will be communicated in writing: Participants with dedifferentiated liposarcoma who have not received prior treatment with a Programmed death ligand 1 (PD-L1) inhibitor; Participants with melanoma who have received a prior PD-L1 inhibitor, had a CR, PR or SD and subsequently progressed while on PD-L1 therapy. Participants who have received prior treatment with a PD-L1 inhibitor must have documented disease progression as defined by meeting all of the following criteria: Has received at least 2 doses of an approved PD-L1 inhibitor; has demonstrated disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The initial evidence of disease progression is to be confirmed by a second assessment no less than four weeks from the date of the first documented PD , in the absence of rapid clinical progression; Progressive disease has been documented within 18 weeks from the last dose of the PD-L1 inhibitor. * In Parts 1A and 2A, a biopsy of the tumor tissue obtained at anytime from the initial diagnosis to study entry. Although a fresh biopsy obtained during screening is preferred, archival tumor specimen is acceptable if it is not feasible to obtain a fresh biopsy. Participants enrolled in Part 1A or Part 2A Pharmacodynamic Cohorts or in Part 2B of the study must provide a fresh biopsy of a tumor lesion not previously irradiated during the screening period and must agree to provide at least one additional on-treatment biopsy. In addition, an archived tumor tissue should be submitted for Participants in Part 2B, if available. The criterion for collection of fresh biopsies may be waived once GlaxoSmithKline (GSK)has determined an appropriate number of viable tissue samples have been analyzed For Part 1B and Part 2B, any archival tumor specimen must have been obtained within 3 months of starting study drug. * Measurable disease as per RECIST v1.1 * Palpable lesions that are not measurable by radiologic or photographic evaluations may not be utilized as the only measurable lesion. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1. * Life expectancy of at least 12 weeks. * Adequate organ function as defined by System Laboratory Values; Hematologic (Absolute neutrophil count \[ANC\] \>=1.5x10\^9/ liter \[L\], Lymphocyte count \>=800/cubic millimeter \[mm\^3\], Hemoglobin \>=9 grams/deciliter \[g/dL\], Platelets \>=100x10\^9/L), Hepatic (Total bilirubin \<=1.5x upper limit of normal \[ULN\] \[For participants with Gilbert's Syndrome, only if direct bilirubin \<=35 percent (%), \<=3.0xULN\], for Part 1A and 2A: alanine aminotransferase \[ALT\] \<=1.5xULN), Part 2B: ALT \<=2.5xULN; Renal (Serum Creatinine \<=1.5xULN OR Calculated creatinine clearance \[CrCl \>50 mL/min ) and Endocrine (Thyroid stimulating hormone \[TSH\]) within normal limits. If TSH is not within normal limits at baseline, the participant may still be eligible if total triiodothyronine (T3) or free T3 and free thyroxine (T4) are within the normal limits. * QT duration corrected for heart rate by Fridericia's formula (QTcF) \<450 milliseconds (msec) or \<480 msec for participants with bundle branch block. * In France, a participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category. * Female participant: is eligible to participate if she is not pregnant (as confirmed by a negative serum beta-human chorionic gonadotrophin \[beta-hCG\] test), not lactating, and at least one of the following conditions applies: Non-reproductive potential defined as: Pre-menopausal females with one of the following: Documented tubal ligation; Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion ; Hysterectomy; Documented Bilateral Oophorectomy. Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. * Reproductive potential and agrees to follow one of the options listed below in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements from 30 days prior to the first dose of study medication and until 120 days after the last dose of study medication and completion of the follow-up visit. GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP). This list does not apply to FRP with same sex partners, when this is their preferred and usual lifestyle or for participants who are and will continue to be abstinent from penile-vaginal intercourse on a long term and persistent basis: Contraceptive subdermal implant with a \<1% rate of failure per year, as stated in the product label; Intrauterine device or intrauterine system with a \<1% rate of failure per year, as stated in the product label; Oral Contraceptive, either combined or progestogen alone; Injectable progestogen; Contraceptive vaginal ring; Percutaneous contraceptive patches; Male partner sterilization with documentation of azoospermia prior to the female participant's entry into the study, and this male is the sole partner for that participant. These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that participants understand how to properly use these methods of contraception. * Male Participants with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until 120 days after the last dose of study medication: Vasectomy with documentation of azoospermia; Male condom plus partner use of one of the contraceptive options below; Contraceptive subdermal implant with a \<1% rate of failure per year, as stated in the product label; Intrauterine device or intrauterine system with a \<1% rate of failure per year, as stated in the product label; Oral Contraceptive, either combined or progestogen alone Injectable progestogen; Contraceptive vaginal ring; Percutaneous contraceptive patches. These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that participants understand how to properly use these methods of contraception.
Exclusion criteria
* Prior treatment with the following agents (from last dose of prior treatment to first dose of GSK3174998): Tumor necrosis factor receptor (TNFR) agonists, including OX40, CD27, CD137 (4-1BB), CD357 (GITR): at any time; Checkpoint inhibitors, including Programmed death receptor-1 (PD-1), 1, and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors: within 4 weeks; other anticancer therapy, including chemotherapy, targeted therapy, and biological therapy: within 4 weeks or 5 half lives of the drug, whichever is shorter. Prior radiation therapy is permissible if at least one unirradiated measurable lesion is available for assessment via RECIST version 1.1. A wash out of at least two weeks before start of study drug for palliative radiation to the extremities for osseous bone metastases and 4 weeks for radiation to the chest, brain, or visceral organs is required; Investigational therapy: if the participant has participated in a clinical trial and has received an investigational product: within 30 days or 5 half-lives of the investigational product (whichever is shorter). At least 14 days must have passed between the last dose of prior investigational agent and the first dose of study drug. * Prior allogeneic or autologous bone marrow transplantation or other solid organ transplantation. * Toxicity from previous treatment: Participants with \>=Grade 3 toxicity related to prior immunotherapy leading to study treatment discontinuation are not eligible; participants whose toxicity related to prior treatment has not resolved to \<=Grade 1 (except alopecia, hearing loss, grade \<=2 neuropathy or endocrinopathy managed with replacement therapy) are not eligible. * Malignancy other than disease under study, except as noted below: any other malignancy from which the participant has been disease-free for more than 2 years and, in the opinion of the principal investigators and GSK Medical Monitor, will not affect the evaluation of the effects of this clinical trial treatment on currently targeted malignancy, can be included in this clinical trial. * Central nervous system (CNS) metastases, with the following exception: Participants who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids for 2 weeks prior to first dose of study drug. * Has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony stimulating factor \[G-CSF\], granulocyte-macrophage colony-stimulating factor \[GMCSF\], recombinant erythropoietin) within 2 weeks before the first dose of study drug. * Major surgery \<=4 weeks before the first dose of study treatment. Participants must have also fully recovered from any surgery (major or minor) and/or its complications before initiating study treatment. * Active autoimmune disease that has required systemic treatment within the last 2 years (that is with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (example \[e.g.\], thyroxine or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. * Concurrent medical condition requiring the use of systemic immunosuppressive medications within 28 days before the first dose of study treatment. Physiologic doses of corticosteroids for treatment of endocrinopathies or steroids with minimal systemic absorption, including topical, inhaled, or intranasal corticosteroids may be continued if the participant is on a stable dose. * Active infection, known human immunodeficiency virus infection, or positive test for hepatitis B surface antigen or hepatitis C. * Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease per investigator assessment). * Known, current drug or alcohol abuse. * Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction. * Receipt of any live vaccine within 4 weeks. * Recent history of allergen desensitization therapy within 4 weeks of starting study Treatment. * History of severe hypersensitivity to other mAbs. * History or evidence of cardiovascular risk including any of the following: Recent (within the past 6 months) history of serious uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities including second degree (Type II) or third degree atrioventricular block; Documented cardiomyopathy, myocardial infarction, acute coronary syndromes (including unstable angina pectoris), coronary angioplasty, stenting, or bypass grafting within the past 6 months before enrollment; documented congestive heart failure (Class II, III, or IV) as defined by the New York Heart Association functional classification system; recent (within the past 6 months) history of symptomatic pericarditis Current or history of idiopathic pulmonary fibrosis, interstitial lung disease, or organizing pneumonia. * History of (non-infectious) pneumonitis that required steroids or current pneumonitis. * Recent history (within 6 months) of uncontrolled symptomatic ascites or pleural effusions. * Any serious and/or unstable pre-existing medical, psychiatric disorder, or other condition that could interfere with the participant's safety, obtaining informed consent, or compliance to the study procedures. * Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective Institutional Review Board (IRB) approval (by chair or designee) is given allowing exception to this criterion for a specific participant. * History of severe hypersensitivity (\>=Grade 3) to pembrolizumab and/or any of its excipients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 2B: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings | Up to maximum 33 weeks | A 12-lead ECG was obtained after the participant had rested at least 10 minutes in a semi-recumbent or supine position during the study using ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with worst case post Baseline abnormal clinical significant ECG findings are presented. |
| Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE) | Up to maximum 39 weeks | An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward medical occurrence that, at any dose: resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE. |
| Part 2A: Number of Participants With Any SAE and Non-SAE | Up to maximum 105 weeks | An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward medical occurrence that, at any dose: resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE. |
| Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 28 days | An adverse event was considered as DLT if it was considered by the investigator to be clinically relevant and attributed (definitely, probably or possibly) to study treatment, occurred within the first 28 days of the treatment, and met 1 of the following criteria: Hematologic: Febrile neutropenia, Grade4 neutropenia of \>7days requiring Granulocyte colony-stimulating factor (G-CSF), Grade4 anemia of any duration, Grade4 thrombocytopenia of any duration or Grade3 thrombocytopenia with bleeding as described in National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4). Non-hematologic: Grade4 toxicity, Grade3 toxicity that cannot be controlled within 3days, Ocular toxicity of \>=Grade3 or of Grade2 requiring systemic steroids. Any other event results in permanent discontinuation of treatment during the first 4 weeks of treatment or any other event which in the judgment of the investigator and GlaxoSmithKline medical monitor is considered to be a DLT. |
| Part 2A: Number of Participants With Dose Reductions or Delay | Up to maximum 105 weeks | Number of participants who had any dose reduction or dose delay (GSK3174998) due to any reason have been presented. |
| Part 2A: Number of Participants With DLTs | 28 days | An adverse event was considered as DLT if it was considered by the investigator to be clinically relevant and attributed (definitely, probably or possibly) to study treatment, occurred within the first 28 days of the treatment, and met 1 of the following criteria: Hematologic: Febrile neutropenia, Grade4 neutropenia of \>7days requiring Granulocyte colony-stimulating factor (G-CSF), Grade4 anemia of any duration, Grade4 thrombocytopenia of any duration or Grade3 thrombocytopenia with bleeding as described in National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4). Non-hematologic: Grade4 toxicity, Grade3 toxicity that cannot be controlled within 3days, Ocular toxicity of \>=Grade3 or of Grade2 requiring systemic steroids. Any other event results in permanent discontinuation of treatment during the first 4 weeks of treatment or any other event which in the judgment of the investigator and GlaxoSmithKline medical monitor is considered to be a DLT. |
| Part 2B: Number of Participants With DLTs | 28 days | An adverse event was considered as DLT if it was considered by the investigator to be clinically relevant and attributed (definitely, probably or possibly) to study treatment, occurred within the first 28 days of the treatment, and met 1 of the following criteria: Hematologic: Febrile neutropenia, Grade4 neutropenia of \>7days requiring Granulocyte colony-stimulating factor (G-CSF), Grade4 anemia of any duration, Grade4 thrombocytopenia of any duration or Grade3 thrombocytopenia with bleeding as described in National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4). Non-hematologic: Grade4 toxicity, Grade3 toxicity that cannot be controlled within 3days, Ocular toxicity of \>=Grade3 or of Grade2 requiring systemic steroids. Any other event results in permanent discontinuation of treatment during the first 4 weeks of treatment or any other event which in the judgment of the investigator and GlaxoSmithKline medical monitor is considered to be a DLT. |
| Part 1: Number of Participants With Any Adverse Event Leading to Withdrawal (AELD) From the Study | Up to maximum 39 weeks | An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with any adverse event leading to withdrawal from the study is presented. |
| Part 2A: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study | Up to maximum 105 weeks | An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with any adverse event leading to withdrawal from the study is presented. |
| Part 2B: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study | Up to maximum 33 weeks | An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with any adverse event leading to withdrawal from the study is presented. |
| Part 1: Number of Participants With Dose Reductions or Delay | Up to maximum 39 weeks | Number of participants who had any dose reduction or dose delay (GSK3174998) due to any reason have been presented. |
| Part 2B: Number of Participants With Dose Reductions or Delay | Up to maximum 33 weeks | Number of participants who had any dose reduction or dose delay (GSK3174998) due to any reason have been presented. |
| Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Baseline (Day 1) and up to maximum 39 weeks | Blood samples were collected for the analysis of following hematology parameters: hemoglobin (Hb), leukocyte count (leuko.), lymphocyte count (Lymph.), neutrophil count (Neutro.) and platelet count (PC). The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented. |
| Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Baseline (Day 1) and up to maximum 105 weeks | Blood samples were collected for the analysis of following hematology parameters: Hb, leuko., Lymph., Neutro. and PC. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented. |
| Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Baseline (Day 1) and up to maximum 33 weeks | Blood samples were collected for the analysis of following hematology parameters: Hb, leuko., Lymph., Neutro. and PC. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented. |
| Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | Baseline (Day 1) and up to maximum 39 weeks | Blood samples were collected for the analysis of following liver function laboratory parameters: alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and bilirubin. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented. |
| Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | Baseline (Day 1) and up to maximum 105 weeks | Blood samples were collected for the analysis of following liver function laboratory parameters: ALT, ALP, AST and bilirubin. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented. |
| Part 2B: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | Baseline (Day 1) and up to maximum 33 weeks | Blood samples were collected for the analysis of following liver function laboratory parameters: ALT, ALP, AST and bilirubin. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented. |
| Part 1: Number of Participants With Any Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Baseline (Day 1) and up to maximum 39 weeks | SBP and DBP were graded using NCI-CTCAE version 4. For SBP: Grade 0: \<120 millimeter mercury (mmHg); Grade 1: 120-139 mmHg; Grade 2: 140-159 mmHg; Grade 3: \>=160 mmHg. For DBP: Grade 0: \<80 mmHg; Grade 1: 80-89 mmHg; Grade 2: 90-99 mmHg; Grade 3: \>=100 mmHg. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented. |
| Part 2A: Number of Participants With Any Grade Change From Baseline in SBP and DBP | Baseline (Day 1) and up to maximum 105 weeks | SBP and DBP were graded using NCI-CTCAE version 4. For SBP: Grade 0: \<120 mmHg; Grade 1: 120-139 mmHg; Grade 2: 140-159 mmHg; Grade 3: \>=160 mmHg. For DBP: Grade 0: \<80 mmHg; Grade 1: 80-89 mmHg; Grade 2: 90-99 mmHg; Grade 3: \>=100 mmHg. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented. |
| Part 2B: Number of Participants With Any Grade Change From Baseline in SBP and DBP | Baseline (Day 1) and up to maximum 33 weeks | SBP and DBP were graded using NCI-CTCAE version 4. For SBP: Grade 0: \<120 mmHg; Grade 1: 120-139 mmHg; Grade 2: 140-159 mmHg; Grade 3: \>=160 mmHg. For DBP: Grade 0: \<80 mmHg; Grade 1: 80-89 mmHg; Grade 2: 90-99 mmHg; Grade 3: \>=100 mmHg. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented. |
| Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Baseline (Day 1) and up to maximum 39 weeks | Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in heart rate is presented. Data was categorized as: heart rate 'decrease to low', 'increase to high' and 'change to normal or no change'; where low HR: \<60 beats per minute \[bpm\]', normal HR: 60 to 100 bpm and high HR: \>100 bpm. If values were unchanged (example: increase to \>100 bpm to increase to \>100 bpm), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%. |
| Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Baseline (Day 1) and up to maximum 105 weeks | Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in heart rate is presented. Data was categorized as: heart rate 'decrease to low', 'increase to high' and 'change to normal or no change'; where low HR: \<60 bpm', normal HR: 60 to 100 bpm and high HR: \>100 bpm. If values were unchanged (example: increase to \>100 bpm to increase to \>100 bpm), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%. |
| Part 2B: Number of Participants With Worst Case Change From Baseline in HR | Baseline (Day 1) and up to maximum 33 weeks | Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in heart rate is presented. Data was categorized as: heart rate 'decrease to low', 'increase to high' and 'change to normal or no change'; where low HR: \<60 bpm', normal HR: 60 to 100 bpm and high HR: \>100 bpm. If values were unchanged (example: increase to \>100 bpm to increase to \>100 bpm), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%. |
| Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Baseline (Day 1) and up to maximum 39 weeks | Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in body temperature is presented. Data was categorized as: 'decrease to low', 'increase to high' and 'change to normal or no change'; where low body temperature: \<=35 degrees Celsius, normal body temperature: 35 to 38 degrees Celsius and high body temperature: \>=38 degrees Celsius. If values were unchanged (example: increase to \>=38 degrees Celsius to increase to \>=38 degrees Celsius), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%. |
| Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Baseline (Day 1) and up to maximum 105 weeks | Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in body temperature is presented. Data was categorized as: 'decrease to low', 'increase to high' and 'change to normal or no change'; where low body temperature: \<=35 degrees Celsius, normal body temperature: 35 to 38 degrees Celsius and high body temperature: \>=38 degrees Celsius. If values were unchanged (example: increase to \>=38 degrees Celsius to increase to \>=38 degrees Celsius), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%. |
| Part 2B: Number of Participants With Worst Case Change From Baseline in Body Temperature | Baseline (Day 1) and up to maximum 33 weeks | Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in body temperature is presented. Data was categorized as: 'decrease to low', 'increase to high' and 'change to normal or no change'; where low body temperature: \<=35 degrees Celsius, normal body temperature: 35 to 38 degrees Celsius and high body temperature: \>=38 degrees Celsius. If values were unchanged (example: increase to \>=38 degrees Celsius to increase to \>=38 degrees Celsius), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%. |
| Part 1: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant Electrocardiogram (ECG) Findings | Up to maximum 39 weeks | A 12-lead ECG was obtained after the participant had rested at least 10 minutes in a semi-recumbent or supine position during the study using ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with worst case post Baseline abnormal clinical significant ECG findings are presented. |
| Part 2A: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings | Up to maximum 105 weeks | A 12-lead ECG was obtained after the participant had rested at least 10 minutes in a semi-recumbent or supine position during the study using ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with worst case post Baseline abnormal clinical significant ECG findings are presented. |
| Part 2B: Number of Participants With Any SAE and Non-SAE | Up to maximum 33 weeks | An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward medical occurrence that, at any dose: resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2A: Objective Response Rate (ORR) | Up to maximum 105 weeks | ORR is defined as the percentage of participants achieving a confirmed CR or PR as the BOR, as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter. PR: \>=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart. |
| Part 2B: Objective Response Rate (ORR) | Up to maximum 33 weeks | ORR is defined as the percentage of participants achieving a confirmed CR or PR as the BOR, as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter. PR: \>=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart. |
| Part 1: Disease Control Rate (DCR) | Up to maximum 39 weeks | DCR is defined as the percentage of participants with a confirmed CR or PR at any time, plus stable disease (SD) \>=12 weeks as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter. PR: \>=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart. SD: 30% decrease in tumor burden compared with Baseline cannot be established nor 20% increase compared with nadir. |
| Part 2A: Disease Control Rate (DCR) | Up to maximum 105 weeks | DCR is defined as the percentage of participants with a confirmed CR or PR at any time, plus SD \>=12 weeks as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter. PR: \>=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart. SD: 30% decrease in tumor burden compared with Baseline cannot be established nor 20% increase compared with nadir. |
| Part 2B: Disease Control Rate (DCR) | Up to maximum 33 weeks | DCR is defined as the percentage of participants with a confirmed CR or PR at any time, plus SD \>=12 weeks as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter. PR: \>=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart. SD: 30% decrease in tumor burden compared with Baseline cannot be established nor 20% increase compared with nadir. |
| Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion | Blood samples for pharmacokinetic (PK) analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion (EOI); anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion. |
| Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion | Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion (EOI); anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion. |
| Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion | Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion (EOI); anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion. |
| Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK3174998 | Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days) | Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods. |
| Part 2A: AUC(0-tau) of GSK3174998 | Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days) | Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods. |
| Part 2B: AUC(0-tau) of GSK3174998 | Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days) | Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods. |
| Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days) | Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods. |
| Part 2A: Cmax and Cmin of GSK3174998 | Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days) | Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods. |
| Part 2B: Cmax and Cmin of GSK3174998 | Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days) | Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods. |
| Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22, 64, 106 | Blood samples for PK analysis of pembrolizumab were collected on Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion (EOPI); anytime on Days 8,15; Pre-dose on Days 22, 64, 106. |
| Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22, 64, 106 | Blood samples for PK analysis of pembrolizumab were collected on Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15; Pre-dose on Days 22, 64, 106. |
| Part 2A: AUC(0-tau) of Pembrolizumab | Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days) | Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods. |
| Part 2B: AUC(0-tau) of Pembrolizumab | Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days) | Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods. |
| Part 2A: Cmax of Pembrolizumab | Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days) | Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods. |
| Part 2B: Cmax of Pembrolizumab | Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days) | Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods. |
| Part 2A: Cmin of Pembrolizumab | Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22; Cycle 3 (Day 64), Cycle 5 (Day 106) (each dosing cycle was of 21 days) | Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15; Pre-dose on Days 22; Cycle 3 (Day 64), Cycle 5 (Day 106) (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods. |
| Part 2B: Cmin of Pembrolizumab | Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22; Cycle 3 (Day 64), Cycle 5 (Day 106) (each dosing cycle was of 21 days) | Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15; Pre-dose on Days 22; Cycle 3 (Day 64), Cycle 5 (Day 106) (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods. |
| Part 1: Number of Participants With Positive Antidrug Antibodies (ADAs) Against GSK3174998 | Up to maximum 39 weeks | Serum samples were collected for the determination of anti-GSK3174998 antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. The presence of treatment emergent ADA was determined using a GSK3174998 bridging style ADA assay with a bio-analytically determined cut-point determined during assay validation. Samples taken after dosing with GSK3174998 that had a value at or above the cut-point was considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Number of participants with confirmed positive anti-GSK3174998 antibodies results at any visit during the study have been presented. |
| Part 2A: Number of Participants With Positive ADAs Against GSK3174998 | Up to maximum 105 weeks | Serum samples were collected for the determination of anti-GSK3174998 antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. The presence of treatment emergent ADA was determined using a GSK3174998 bridging style ADA assay with a bio-analytically determined cut-point (determined during assay validation). Samples taken after dosing with GSK3174998 that had a value at or above the cut-point was considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Number of participants with confirmed positive anti-GSK3174998 antibodies results at any visit during the study have been presented. |
| Part 2B: Number of Participants With Positive ADAs Against GSK3174998 | Up to maximum 33 weeks | Serum samples were collected for the determination of anti-GSK3174998 antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. The presence of treatment emergent ADA was determined using a GSK3174998 bridging style ADA assay with a bio-analytically determined cut-point (determined during assay validation). Samples taken after dosing with GSK3174998 that had a value at or above the cut-point was considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Number of participants with confirmed positive anti-GSK3174998 antibodies results at any visit during the study have been presented. |
| Part 2A: Number of Participants With Positive ADAs Against Pembrolizumab | Up to maximum 105 weeks | Serum samples were collected for the determination of anti-pembrolizumab antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. The presence of treatment emergent ADA was determined using a pembrolizumab bridging style ADA assay with a bio-analytically determined cut-point (determined during assay validation). Samples taken after dosing with pembrolizumab that had a value at or above the cut-point was considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Number of participants with confirmed positive anti-pembrolizumab antibodies results at any visit during the study have been presented. |
| Part 2B: Number of Participants With Positive ADAs Against Pembrolizumab | Up to maximum 33 weeks | Serum samples were planned to be collected for the determination of anti-pembrolizumab antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. |
| Part 1: Objective Response Rate (ORR) | Up to maximum 39 weeks | ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or a partial response (PR) as the Best Overall Response (BOR), as assessed by the investigator per Response Evaluation Criteria In Solid Tumors (RECIST) Version (v) 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter. PR: \>=30 percent (%) decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart. |
Countries
Canada, France, Netherlands, United States
Participant flow
Recruitment details
This was a 2 part study conducted across 4 countries. Part 1 was dose-escalation study to evaluate GSK3174998 monotherapy. Part 2 included dose-escalation cohorts of GSK3174998+pembrolizumab combination therapy (Comb. Th.) (Part 2A) and dose-expansion (Expan.) disease specific cohorts (Coh.) of GSK3174998 + pembrolizumab (Part 2B).
Pre-assignment details
A total of 141 participants were enrolled in the study: 45 participants in Part 1 and 96 participants in Part 2 (74 in Part 2A+ 22 in Part 2B).
Participants by arm
| Arm | Count |
|---|---|
| Part 1: GSK3174998 0.003 mg/kg Participants received intravenous (IV) dose of GSK3174998 0.003 milligram per kilogram (mg/kg) every 3 weeks (wks) in Part 1. | 1 |
| Part 1: GSK3174998 0.01 mg/kg Participants received IV dose of GSK3174998 0.01 mg/kg every 3 weeks (Q3W) in Part 1. | 1 |
| Part 1: GSK3174998 0.03 mg/kg Participants received IV dose of GSK3174998 0.03 mg/kg Q3W in Part 1. | 8 |
| Part 1: GSK3174998 0.1 mg/kg Participants received IV dose of GSK3174998 0.1 mg/kg Q3W in Part 1. | 10 |
| Part 1: GSK3174998 0.3 mg/kg Participants received IV dose of GSK3174998 0.3 mg/kg Q3W in Part 1. | 10 |
| Part 1: GSK3174998 1.0 mg/kg Participants received IV dose of GSK3174998 1.0 mg/kg Q3W in Part 1. | 4 |
| Part 1: GSK3174998 3.0 mg/kg Participants received IV dose of GSK3174998 3.0 mg/kg Q3W in Part 1. | 7 |
| Part 1: GSK3174998 10.0 mg/kg Participants received IV dose of GSK3174998 10.0 mg/kg Q3W in Part 1. | 4 |
| Part 2A: GSK3174998 0.003 mg/kg + Pembrolizumab 200 mg Participants received IV dose of GSK3174998 0.003 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A. | 5 |
| Part 2A: GSK3174998 0.01 mg/kg + Pembrolizumab 200 mg Participants received IV dose of GSK3174998 0.01 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A. | 5 |
| Part 2A: GSK3174998 0.03 mg/kg + Pembrolizumab 200 mg Participants received IV dose of GSK3174998 0.03 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A. | 10 |
| Part 2A: GSK3174998 0.1 mg/kg + Pembrolizumab 200 mg Participants received IV dose of GSK3174998 0.1 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A. | 12 |
| Part 2A: GSK3174998 0.3 mg/kg + Pembrolizumab 200 mg Participants received IV dose of GSK3174998 0.3 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A. | 14 |
| Part 2A: GSK3174998 1.0 mg/kg + Pembrolizumab 200 mg Participants received IV dose of GSK3174998 1.0 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A. | 12 |
| Part 2A: GSK3174998 3.0 mg/kg + Pembrolizumab 200 mg Participants received IV dose of GSK3174998 3.0 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A. | 12 |
| Part 2A: GSK3174998 10.0 mg/kg + Pembrolizumab 200 mg Participants received IV dose of GSK3174998 10.0 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2A. | 4 |
| Part 2B: Melanoma Cohort Participants with melanoma were included in this cohort and received IV dose of GSK3174998 0.3 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2B. | 9 |
| Part 2B: Soft Tissue Sarcoma Cohort Participants with soft tissue sarcoma were included in this cohort and received IV dose of GSK3174998 0.3 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2B. | 8 |
| Part 2B: NSCLC Cohort Participants with non-small cell lung cancer (NSCLC) were included in this cohort and received IV dose of GSK3174998 0.3 mg/kg + pembrolizumab 200 mg IV Q3W in Part 2B. | 5 |
| Total | 141 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part1:Monotherapy(Up to Maximum 39weeks) | Follow-up assessments removed (Protocol Amendment 4) | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part1:Monotherapy(Up to Maximum 39weeks) | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part1:Monotherapy(Up to Maximum 39weeks) | Physician Decision | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part1:Monotherapy(Up to Maximum 39weeks) | Withdrawal by Subject | 0 | 0 | 2 | 0 | 3 | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part2A:Comb. Th. (Up to Maximum 105wks) | Follow-up assessments removed (Protocol Amendment 4) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 3 | 4 | 1 | 1 | 0 | 0 | 0 | 0 |
| Part2A:Comb. Th. (Up to Maximum 105wks) | Investigator site closed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 5 | 0 | 0 | 0 | 0 |
| Part2A:Comb. Th. (Up to Maximum 105wks) | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part2A:Comb. Th. (Up to Maximum 105wks) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 1 | 3 | 1 | 0 | 0 | 0 | 0 |
| Part2B:Expan. Coh.(Up to Maximum 33 Wks) | Follow-up assessments removed (Protocol Amendment 4) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 4 | 3 |
| Part2B:Expan. Coh.(Up to Maximum 33 Wks) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1: GSK3174998 0.01 mg/kg | Part 1: GSK3174998 0.03 mg/kg | Part 1: GSK3174998 0.1 mg/kg | Part 1: GSK3174998 0.3 mg/kg | Part 1: GSK3174998 1.0 mg/kg | Part 1: GSK3174998 3.0 mg/kg | Part 1: GSK3174998 10.0 mg/kg | Part 2A: GSK3174998 0.003 mg/kg + Pembrolizumab 200 mg | Part 2A: GSK3174998 0.01 mg/kg + Pembrolizumab 200 mg | Part 2A: GSK3174998 0.03 mg/kg + Pembrolizumab 200 mg | Part 1: GSK3174998 0.003 mg/kg | Part 2A: GSK3174998 0.1 mg/kg + Pembrolizumab 200 mg | Part 2A: GSK3174998 0.3 mg/kg + Pembrolizumab 200 mg | Part 2A: GSK3174998 1.0 mg/kg + Pembrolizumab 200 mg | Part 2A: GSK3174998 3.0 mg/kg + Pembrolizumab 200 mg | Part 2A: GSK3174998 10.0 mg/kg + Pembrolizumab 200 mg | Part 2B: Melanoma Cohort | Part 2B: Soft Tissue Sarcoma Cohort | Part 2B: NSCLC Cohort | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18 to 64 years | 0 Participants | 5 Participants | 8 Participants | 4 Participants | 2 Participants | 4 Participants | 2 Participants | 1 Participants | 3 Participants | 6 Participants | 1 Participants | 6 Participants | 8 Participants | 6 Participants | 6 Participants | 1 Participants | 6 Participants | 5 Participants | 2 Participants | 76 Participants |
| Age, Customized 65 to 84 years | 1 Participants | 3 Participants | 2 Participants | 6 Participants | 2 Participants | 3 Participants | 2 Participants | 4 Participants | 2 Participants | 4 Participants | 0 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 64 Participants |
| Age, Customized >=85 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race African American/African Heritage | NA Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | NA Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | NA Participants |
| Race/Ethnicity, Customized Race Asian - Central/South Asian Heritage | NA Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | NA Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | NA Participants |
| Race/Ethnicity, Customized Race Asian - East Asian Heritage | NA Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | NA Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | NA Participants |
| Race/Ethnicity, Customized Race Asian - South East Asian Heritage | NA Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | NA Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | NA Participants |
| Race/Ethnicity, Customized Race Missing | NA Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | NA Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | NA Participants |
| Race/Ethnicity, Customized Race White - Arabic/North African Heritage | NA Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | NA Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | NA Participants |
| Race/Ethnicity, Customized Race White - White/Caucasian/European Heritage | NA Participants | 6 Participants | 7 Participants | 10 Participants | 4 Participants | 7 Participants | 3 Participants | 5 Participants | 5 Participants | 10 Participants | NA Participants | 12 Participants | 12 Participants | 7 Participants | 10 Participants | 2 Participants | 9 Participants | 6 Participants | 4 Participants | NA Participants |
| Sex: Female, Male Female | NA Participants | 6 Participants | 6 Participants | 5 Participants | 1 Participants | 6 Participants | 3 Participants | 3 Participants | 3 Participants | 8 Participants | NA Participants | 5 Participants | 6 Participants | 3 Participants | 8 Participants | 0 Participants | 3 Participants | 4 Participants | 1 Participants | NA Participants |
| Sex: Female, Male Male | NA Participants | 2 Participants | 4 Participants | 5 Participants | 3 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | NA Participants | 7 Participants | 8 Participants | 9 Participants | 4 Participants | 4 Participants | 6 Participants | 4 Participants | 4 Participants | NA Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 1 | 0 / 1 | 6 / 8 | 9 / 10 | 6 / 10 | 2 / 4 | 5 / 7 | 2 / 4 | 4 / 5 | 4 / 5 | 7 / 10 | 9 / 12 | 9 / 14 | 6 / 12 | 5 / 12 | 4 / 4 | 6 / 9 | 4 / 8 | 2 / 5 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 8 / 8 | 10 / 10 | 10 / 10 | 4 / 4 | 7 / 7 | 4 / 4 | 5 / 5 | 5 / 5 | 10 / 10 | 12 / 12 | 13 / 14 | 12 / 12 | 12 / 12 | 4 / 4 | 9 / 9 | 8 / 8 | 4 / 5 |
| serious Total, serious adverse events | 1 / 1 | 0 / 1 | 3 / 8 | 7 / 10 | 2 / 10 | 1 / 4 | 2 / 7 | 1 / 4 | 1 / 5 | 1 / 5 | 6 / 10 | 4 / 12 | 4 / 14 | 4 / 12 | 2 / 12 | 2 / 4 | 1 / 9 | 2 / 8 | 1 / 5 |
Outcome results
Primary
Part 1: Number of Participants With Any Adverse Event Leading to Withdrawal (AELD) From the Study
An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with any adverse event leading to withdrawal from the study is presented.
Time frame: Up to maximum 39 weeks
Population: All Treated Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Any Adverse Event Leading to Withdrawal (AELD) From the Study | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Any Adverse Event Leading to Withdrawal (AELD) From the Study | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Any Adverse Event Leading to Withdrawal (AELD) From the Study | 0 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Any Adverse Event Leading to Withdrawal (AELD) From the Study | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Any Adverse Event Leading to Withdrawal (AELD) From the Study | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Any Adverse Event Leading to Withdrawal (AELD) From the Study | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Any Adverse Event Leading to Withdrawal (AELD) From the Study | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Any Adverse Event Leading to Withdrawal (AELD) From the Study | 0 Participants |
Primary
Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters
Blood samples were collected for the analysis of following hematology parameters: hemoglobin (Hb), leukocyte count (leuko.), lymphocyte count (Lymph.), neutrophil count (Neutro.) and platelet count (PC). The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Time frame: Baseline (Day 1) and up to maximum 39 weeks
Population: All Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. increased | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb increased | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb decreased (anemia) | 1 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. decreased | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. decreased | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. increased | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Neutro. decreased | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | PC decreased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. decreased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. increased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. increased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Neutro. decreased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb decreased (anemia) | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. decreased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb increased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | PC decreased | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Neutro. decreased | 1 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. decreased | 5 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | PC decreased | 1 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. increased | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. increased | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. decreased | 2 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb decreased (anemia) | 7 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb increased | 1 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | PC decreased | 1 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb increased | 0 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb decreased (anemia) | 6 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. decreased | 2 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. increased | 0 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. decreased | 3 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. increased | 0 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Neutro. decreased | 1 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. decreased | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Neutro. decreased | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. increased | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb decreased (anemia) | 5 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | PC decreased | 1 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. decreased | 6 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. increased | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb increased | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | PC decreased | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb increased | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. increased | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb decreased (anemia) | 3 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Neutro. decreased | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. increased | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. decreased | 1 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. decreased | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. increased | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb increased | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. decreased | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. decreased | 5 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. increased | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | PC decreased | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Neutro. decreased | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb decreased (anemia) | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | PC decreased | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. increased | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. decreased | 3 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. decreased | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. increased | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb increased | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb decreased (anemia) | 1 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Neutro. decreased | 0 Participants |
Primary
Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters
Blood samples were collected for the analysis of following liver function laboratory parameters: alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and bilirubin. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Time frame: Baseline (Day 1) and up to maximum 39 weeks
Population: All Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALT increased | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALP increased | 1 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | AST increased | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | Bilirubin increased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | Bilirubin increased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALP increased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALT increased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | AST increased | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALT increased | 1 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | Bilirubin increased | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALP increased | 3 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | AST increased | 3 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALT increased | 2 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALP increased | 3 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | AST increased | 5 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | Bilirubin increased | 1 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | Bilirubin increased | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | AST increased | 1 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALP increased | 5 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALT increased | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | Bilirubin increased | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | AST increased | 2 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALP increased | 1 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALT increased | 2 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | Bilirubin increased | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALT increased | 1 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | AST increased | 3 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALP increased | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALP increased | 2 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | AST increased | 3 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | Bilirubin increased | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALT increased | 1 Participants |
Primary
Part 1: Number of Participants With Any Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP and DBP were graded using NCI-CTCAE version 4. For SBP: Grade 0: \<120 millimeter mercury (mmHg); Grade 1: 120-139 mmHg; Grade 2: 140-159 mmHg; Grade 3: \>=160 mmHg. For DBP: Grade 0: \<80 mmHg; Grade 1: 80-89 mmHg; Grade 2: 90-99 mmHg; Grade 3: \>=100 mmHg. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Time frame: Baseline (Day 1) and up to maximum 39 weeks
Population: All Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP | 1 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP | 6 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP | 4 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP | 3 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP | 5 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP | 5 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP | 5 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP | 2 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP | 2 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP | 2 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP | 6 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP | 3 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Any Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP | 2 Participants |
Primary
Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE)
An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward medical occurrence that, at any dose: resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE.
Time frame: Up to maximum 39 weeks
Population: All Treated Population consisted of all participants who received at least one dose of GSK3174998.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE) | Any SAE | 1 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE) | Any non-SAE | 1 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE) | Any SAE | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE) | Any non-SAE | 1 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE) | Any SAE | 3 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE) | Any non-SAE | 8 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE) | Any SAE | 7 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE) | Any non-SAE | 10 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE) | Any SAE | 2 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE) | Any non-SAE | 10 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE) | Any SAE | 1 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE) | Any non-SAE | 4 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE) | Any non-SAE | 7 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE) | Any SAE | 2 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE) | Any SAE | 1 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE) | Any non-SAE | 4 Participants |
Primary
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
An adverse event was considered as DLT if it was considered by the investigator to be clinically relevant and attributed (definitely, probably or possibly) to study treatment, occurred within the first 28 days of the treatment, and met 1 of the following criteria: Hematologic: Febrile neutropenia, Grade4 neutropenia of \>7days requiring Granulocyte colony-stimulating factor (G-CSF), Grade4 anemia of any duration, Grade4 thrombocytopenia of any duration or Grade3 thrombocytopenia with bleeding as described in National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4). Non-hematologic: Grade4 toxicity, Grade3 toxicity that cannot be controlled within 3days, Ocular toxicity of \>=Grade3 or of Grade2 requiring systemic steroids. Any other event results in permanent discontinuation of treatment during the first 4 weeks of treatment or any other event which in the judgment of the investigator and GlaxoSmithKline medical monitor is considered to be a DLT.
Time frame: 28 days
Population: All Treated Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
Primary
Part 1: Number of Participants With Dose Reductions or Delay
Number of participants who had any dose reduction or dose delay (GSK3174998) due to any reason have been presented.
Time frame: Up to maximum 39 weeks
Population: All Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Dose Reductions or Delay | Dose reduction | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Dose Reductions or Delay | Dose delay | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Dose Reductions or Delay | Dose reduction | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Dose Reductions or Delay | Dose delay | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Dose Reductions or Delay | Dose reduction | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Dose Reductions or Delay | Dose delay | 0 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Dose Reductions or Delay | Dose reduction | 0 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Dose Reductions or Delay | Dose delay | 1 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Dose Reductions or Delay | Dose reduction | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Dose Reductions or Delay | Dose delay | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Dose Reductions or Delay | Dose reduction | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Dose Reductions or Delay | Dose delay | 1 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Dose Reductions or Delay | Dose delay | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Dose Reductions or Delay | Dose reduction | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Dose Reductions or Delay | Dose reduction | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Dose Reductions or Delay | Dose delay | 0 Participants |
Primary
Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in body temperature is presented. Data was categorized as: 'decrease to low', 'increase to high' and 'change to normal or no change'; where low body temperature: \<=35 degrees Celsius, normal body temperature: 35 to 38 degrees Celsius and high body temperature: \>=38 degrees Celsius. If values were unchanged (example: increase to \>=38 degrees Celsius to increase to \>=38 degrees Celsius), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.
Time frame: Baseline (Day 1) and up to maximum 39 weeks
Population: All Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Decrease to low | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Increase to high | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Change to normal or no change | 1 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Increase to high | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Change to normal or no change | 1 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Decrease to low | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Increase to high | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Decrease to low | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Change to normal or no change | 8 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Decrease to low | 0 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Change to normal or no change | 8 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Increase to high | 2 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Change to normal or no change | 9 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Decrease to low | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Increase to high | 1 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Change to normal or no change | 3 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Decrease to low | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Increase to high | 1 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Change to normal or no change | 7 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Decrease to low | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Increase to high | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Decrease to low | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Change to normal or no change | 4 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature | Increase to high | 0 Participants |
Primary
Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR)
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in heart rate is presented. Data was categorized as: heart rate 'decrease to low', 'increase to high' and 'change to normal or no change'; where low HR: \<60 beats per minute \[bpm\]', normal HR: 60 to 100 bpm and high HR: \>100 bpm. If values were unchanged (example: increase to \>100 bpm to increase to \>100 bpm), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.
Time frame: Baseline (Day 1) and up to maximum 39 weeks
Population: All Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Decrease to low | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Increase to high | 1 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Change to normal or no change | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Increase to high | 1 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Change to normal or no change | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Decrease to low | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Increase to high | 3 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Decrease to low | 1 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Change to normal or no change | 4 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Decrease to low | 2 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Change to normal or no change | 3 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Increase to high | 6 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Change to normal or no change | 4 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Decrease to low | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Increase to high | 6 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Change to normal or no change | 2 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Decrease to low | 1 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Increase to high | 1 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Change to normal or no change | 4 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Decrease to low | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Increase to high | 3 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Decrease to low | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Change to normal or no change | 2 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) | Increase to high | 2 Participants |
Primary
Part 1: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant Electrocardiogram (ECG) Findings
A 12-lead ECG was obtained after the participant had rested at least 10 minutes in a semi-recumbent or supine position during the study using ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with worst case post Baseline abnormal clinical significant ECG findings are presented.
Time frame: Up to maximum 39 weeks
Population: All Treated Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
Primary
Part 2A: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study
An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with any adverse event leading to withdrawal from the study is presented.
Time frame: Up to maximum 105 weeks
Population: All Treated Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study | 0 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study | 1 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study | 0 Participants |
Primary
Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters
Blood samples were collected for the analysis of following hematology parameters: Hb, leuko., Lymph., Neutro. and PC. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Time frame: Baseline (Day 1) and up to maximum 105 weeks
Population: All Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb decreased (anemia) | 2 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. increased | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb increased | 1 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | PC decreased | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. increased | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. decreased | 1 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. decreased | 2 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Neutro. decreased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | PC decreased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. increased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. increased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. decreased | 2 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. decreased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb increased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb decreased (anemia) | 2 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Neutro. decreased | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb increased | 1 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Neutro. decreased | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | PC decreased | 1 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. decreased | 5 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb decreased (anemia) | 2 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. increased | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. increased | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. decreased | 1 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. increased | 0 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb decreased (anemia) | 5 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. decreased | 2 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb increased | 1 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Neutro. decreased | 0 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. increased | 0 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. decreased | 0 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | PC decreased | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. increased | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. decreased | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. decreased | 6 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb increased | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb decreased (anemia) | 4 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Neutro. decreased | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | PC decreased | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. increased | 1 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. decreased | 1 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. increased | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. decreased | 4 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. increased | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Neutro. decreased | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | PC decreased | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb decreased (anemia) | 3 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb increased | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. decreased | 3 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | PC decreased | 2 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Neutro. decreased | 2 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. increased | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. decreased | 3 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. increased | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb increased | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb decreased (anemia) | 5 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | PC decreased | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. decreased | 1 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. decreased | 2 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. increased | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Neutro. decreased | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. increased | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb decreased (anemia) | 1 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb increased | 0 Participants |
Primary
Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters
Blood samples were collected for the analysis of following liver function laboratory parameters: ALT, ALP, AST and bilirubin. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Time frame: Baseline (Day 1) and up to maximum 105 weeks
Population: All Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALT increased | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALP increased | 1 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | AST increased | 1 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | Bilirubin increased | 1 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | Bilirubin increased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALP increased | 3 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALT increased | 1 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | AST increased | 3 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALT increased | 1 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | Bilirubin increased | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALP increased | 4 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | AST increased | 2 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALT increased | 3 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALP increased | 1 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | AST increased | 1 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | Bilirubin increased | 3 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | Bilirubin increased | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | AST increased | 6 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALP increased | 3 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALT increased | 4 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | Bilirubin increased | 1 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | AST increased | 3 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALP increased | 2 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALT increased | 2 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | Bilirubin increased | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALT increased | 2 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | AST increased | 3 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALP increased | 4 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALP increased | 1 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | AST increased | 1 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | Bilirubin increased | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALT increased | 1 Participants |
Primary
Part 2A: Number of Participants With Any Grade Change From Baseline in SBP and DBP
SBP and DBP were graded using NCI-CTCAE version 4. For SBP: Grade 0: \<120 mmHg; Grade 1: 120-139 mmHg; Grade 2: 140-159 mmHg; Grade 3: \>=160 mmHg. For DBP: Grade 0: \<80 mmHg; Grade 1: 80-89 mmHg; Grade 2: 90-99 mmHg; Grade 3: \>=100 mmHg. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Time frame: Baseline (Day 1) and up to maximum 105 weeks
Population: All Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in SBP and DBP | SBP | 2 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in SBP and DBP | DBP | 1 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in SBP and DBP | SBP | 4 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in SBP and DBP | DBP | 4 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in SBP and DBP | SBP | 8 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in SBP and DBP | DBP | 7 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in SBP and DBP | SBP | 6 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in SBP and DBP | DBP | 6 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in SBP and DBP | SBP | 6 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in SBP and DBP | DBP | 6 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in SBP and DBP | SBP | 7 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in SBP and DBP | DBP | 5 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in SBP and DBP | DBP | 4 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in SBP and DBP | SBP | 7 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in SBP and DBP | SBP | 1 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Any Grade Change From Baseline in SBP and DBP | DBP | 0 Participants |
Primary
Part 2A: Number of Participants With Any SAE and Non-SAE
An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward medical occurrence that, at any dose: resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE.
Time frame: Up to maximum 105 weeks
Population: All Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Any SAE and Non-SAE | Any SAE | 1 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Any SAE and Non-SAE | Any non-SAE | 5 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Any SAE and Non-SAE | Any SAE | 1 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Any SAE and Non-SAE | Any non-SAE | 5 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Any SAE and Non-SAE | Any SAE | 6 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Any SAE and Non-SAE | Any non-SAE | 10 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Any SAE and Non-SAE | Any SAE | 4 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Any SAE and Non-SAE | Any non-SAE | 12 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Any SAE and Non-SAE | Any SAE | 4 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Any SAE and Non-SAE | Any non-SAE | 13 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Any SAE and Non-SAE | Any SAE | 4 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Any SAE and Non-SAE | Any non-SAE | 12 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Any SAE and Non-SAE | Any non-SAE | 12 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Any SAE and Non-SAE | Any SAE | 2 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Any SAE and Non-SAE | Any SAE | 2 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Any SAE and Non-SAE | Any non-SAE | 4 Participants |
Primary
Part 2A: Number of Participants With DLTs
An adverse event was considered as DLT if it was considered by the investigator to be clinically relevant and attributed (definitely, probably or possibly) to study treatment, occurred within the first 28 days of the treatment, and met 1 of the following criteria: Hematologic: Febrile neutropenia, Grade4 neutropenia of \>7days requiring Granulocyte colony-stimulating factor (G-CSF), Grade4 anemia of any duration, Grade4 thrombocytopenia of any duration or Grade3 thrombocytopenia with bleeding as described in National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4). Non-hematologic: Grade4 toxicity, Grade3 toxicity that cannot be controlled within 3days, Ocular toxicity of \>=Grade3 or of Grade2 requiring systemic steroids. Any other event results in permanent discontinuation of treatment during the first 4 weeks of treatment or any other event which in the judgment of the investigator and GlaxoSmithKline medical monitor is considered to be a DLT.
Time frame: 28 days
Population: All Treated Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With DLTs | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With DLTs | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With DLTs | 1 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With DLTs | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With DLTs | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With DLTs | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With DLTs | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With DLTs | 1 Participants |
Primary
Part 2A: Number of Participants With Dose Reductions or Delay
Number of participants who had any dose reduction or dose delay (GSK3174998) due to any reason have been presented.
Time frame: Up to maximum 105 weeks
Population: All Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Dose Reductions or Delay | Dose reduction | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Dose Reductions or Delay | Dose delay | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Dose Reductions or Delay | Dose reduction | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Dose Reductions or Delay | Dose delay | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Dose Reductions or Delay | Dose reduction | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Dose Reductions or Delay | Dose delay | 1 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Dose Reductions or Delay | Dose reduction | 0 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Dose Reductions or Delay | Dose delay | 1 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Dose Reductions or Delay | Dose reduction | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Dose Reductions or Delay | Dose delay | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Dose Reductions or Delay | Dose reduction | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Dose Reductions or Delay | Dose delay | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Dose Reductions or Delay | Dose delay | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Dose Reductions or Delay | Dose reduction | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Dose Reductions or Delay | Dose reduction | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Dose Reductions or Delay | Dose delay | 0 Participants |
Primary
Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in body temperature is presented. Data was categorized as: 'decrease to low', 'increase to high' and 'change to normal or no change'; where low body temperature: \<=35 degrees Celsius, normal body temperature: 35 to 38 degrees Celsius and high body temperature: \>=38 degrees Celsius. If values were unchanged (example: increase to \>=38 degrees Celsius to increase to \>=38 degrees Celsius), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.
Time frame: Baseline (Day 1) and up to maximum 105 weeks
Population: All Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Decrease to low | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Increase to high | 1 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Change to normal or no change | 4 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Increase to high | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Change to normal or no change | 5 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Decrease to low | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Increase to high | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Decrease to low | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Change to normal or no change | 10 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Decrease to low | 0 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Change to normal or no change | 11 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Increase to high | 1 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Change to normal or no change | 12 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Decrease to low | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Increase to high | 2 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Change to normal or no change | 12 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Decrease to low | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Increase to high | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Change to normal or no change | 12 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Decrease to low | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Increase to high | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Decrease to low | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Change to normal or no change | 4 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature | Increase to high | 0 Participants |
Primary
Part 2A: Number of Participants With Worst Case Change From Baseline in HR
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in heart rate is presented. Data was categorized as: heart rate 'decrease to low', 'increase to high' and 'change to normal or no change'; where low HR: \<60 bpm', normal HR: 60 to 100 bpm and high HR: \>100 bpm. If values were unchanged (example: increase to \>100 bpm to increase to \>100 bpm), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.
Time frame: Baseline (Day 1) and up to maximum 105 weeks
Population: All Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Decrease to low | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Increase to high | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Change to normal or no change | 5 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Increase to high | 1 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Change to normal or no change | 4 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Decrease to low | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Increase to high | 2 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Decrease to low | 1 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Change to normal or no change | 7 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Decrease to low | 3 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Change to normal or no change | 6 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Increase to high | 3 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Change to normal or no change | 8 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Decrease to low | 4 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Increase to high | 2 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Change to normal or no change | 8 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Decrease to low | 1 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Increase to high | 3 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Change to normal or no change | 6 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Decrease to low | 3 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Increase to high | 3 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Decrease to low | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Change to normal or no change | 4 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Worst Case Change From Baseline in HR | Increase to high | 0 Participants |
Primary
Part 2A: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings
A 12-lead ECG was obtained after the participant had rested at least 10 minutes in a semi-recumbent or supine position during the study using ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with worst case post Baseline abnormal clinical significant ECG findings are presented.
Time frame: Up to maximum 105 weeks
Population: All Treated Population. Only those participants with data available at the indicated data points were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings | 0 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings | 0 Participants |
Primary
Part 2B: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study
An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with any adverse event leading to withdrawal from the study is presented.
Time frame: Up to maximum 33 weeks
Population: All Treated Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study | 0 Participants |
Primary
Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters
Blood samples were collected for the analysis of following hematology parameters: Hb, leuko., Lymph., Neutro. and PC. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Time frame: Baseline (Day 1) and up to maximum 33 weeks
Population: All Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb decreased (anemia) | 2 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb increased | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. increased | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. decreased | 1 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. decreased | 3 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. increased | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Neutro. decreased | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | PC decreased | 1 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. increased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Neutro. decreased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. decreased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. decreased | 3 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. increased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb decreased (anemia) | 2 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb increased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | PC decreased | 1 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. increased | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb increased | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Hb decreased (anemia) | 1 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Leuko. decreased | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Neutro. decreased | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. increased | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | Lymph. decreased | 2 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters | PC decreased | 1 Participants |
Primary
Part 2B: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters
Blood samples were collected for the analysis of following liver function laboratory parameters: ALT, ALP, AST and bilirubin. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Time frame: Baseline (Day 1) and up to maximum 33 weeks
Population: All Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALT increased | 2 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALP increased | 3 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | AST increased | 3 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | Bilirubin increased | 1 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | Bilirubin increased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALT increased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | AST increased | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALP increased | 4 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | Bilirubin increased | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALP increased | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | AST increased | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters | ALT increased | 0 Participants |
Primary
Part 2B: Number of Participants With Any Grade Change From Baseline in SBP and DBP
SBP and DBP were graded using NCI-CTCAE version 4. For SBP: Grade 0: \<120 mmHg; Grade 1: 120-139 mmHg; Grade 2: 140-159 mmHg; Grade 3: \>=160 mmHg. For DBP: Grade 0: \<80 mmHg; Grade 1: 80-89 mmHg; Grade 2: 90-99 mmHg; Grade 3: \>=100 mmHg. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented.
Time frame: Baseline (Day 1) and up to maximum 33 weeks
Population: All Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in SBP and DBP | SBP | 7 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in SBP and DBP | DBP | 5 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in SBP and DBP | SBP | 4 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in SBP and DBP | DBP | 5 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in SBP and DBP | SBP | 4 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Any Grade Change From Baseline in SBP and DBP | DBP | 3 Participants |
Primary
Part 2B: Number of Participants With Any SAE and Non-SAE
An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward medical occurrence that, at any dose: resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE.
Time frame: Up to maximum 33 weeks
Population: All Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Any SAE and Non-SAE | Any SAE | 1 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Any SAE and Non-SAE | Any non-SAE | 9 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Any SAE and Non-SAE | Any SAE | 2 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Any SAE and Non-SAE | Any non-SAE | 8 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Any SAE and Non-SAE | Any SAE | 1 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Any SAE and Non-SAE | Any non-SAE | 4 Participants |
Primary
Part 2B: Number of Participants With DLTs
An adverse event was considered as DLT if it was considered by the investigator to be clinically relevant and attributed (definitely, probably or possibly) to study treatment, occurred within the first 28 days of the treatment, and met 1 of the following criteria: Hematologic: Febrile neutropenia, Grade4 neutropenia of \>7days requiring Granulocyte colony-stimulating factor (G-CSF), Grade4 anemia of any duration, Grade4 thrombocytopenia of any duration or Grade3 thrombocytopenia with bleeding as described in National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4). Non-hematologic: Grade4 toxicity, Grade3 toxicity that cannot be controlled within 3days, Ocular toxicity of \>=Grade3 or of Grade2 requiring systemic steroids. Any other event results in permanent discontinuation of treatment during the first 4 weeks of treatment or any other event which in the judgment of the investigator and GlaxoSmithKline medical monitor is considered to be a DLT.
Time frame: 28 days
Population: All Treated Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With DLTs | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With DLTs | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With DLTs | 0 Participants |
Primary
Part 2B: Number of Participants With Dose Reductions or Delay
Number of participants who had any dose reduction or dose delay (GSK3174998) due to any reason have been presented.
Time frame: Up to maximum 33 weeks
Population: All Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Dose Reductions or Delay | Dose reduction | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Dose Reductions or Delay | Dose delay | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Dose Reductions or Delay | Dose reduction | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Dose Reductions or Delay | Dose delay | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Dose Reductions or Delay | Dose reduction | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Dose Reductions or Delay | Dose delay | 0 Participants |
Primary
Part 2B: Number of Participants With Worst Case Change From Baseline in Body Temperature
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in body temperature is presented. Data was categorized as: 'decrease to low', 'increase to high' and 'change to normal or no change'; where low body temperature: \<=35 degrees Celsius, normal body temperature: 35 to 38 degrees Celsius and high body temperature: \>=38 degrees Celsius. If values were unchanged (example: increase to \>=38 degrees Celsius to increase to \>=38 degrees Celsius), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.
Time frame: Baseline (Day 1) and up to maximum 33 weeks
Population: All Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Worst Case Change From Baseline in Body Temperature | Change to normal or no change | 9 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Worst Case Change From Baseline in Body Temperature | Decrease to low | 0 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Worst Case Change From Baseline in Body Temperature | Increase to high | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Worst Case Change From Baseline in Body Temperature | Change to normal or no change | 8 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Worst Case Change From Baseline in Body Temperature | Decrease to low | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Worst Case Change From Baseline in Body Temperature | Increase to high | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Worst Case Change From Baseline in Body Temperature | Decrease to low | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Worst Case Change From Baseline in Body Temperature | Increase to high | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Worst Case Change From Baseline in Body Temperature | Change to normal or no change | 5 Participants |
Primary
Part 2B: Number of Participants With Worst Case Change From Baseline in HR
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in heart rate is presented. Data was categorized as: heart rate 'decrease to low', 'increase to high' and 'change to normal or no change'; where low HR: \<60 bpm', normal HR: 60 to 100 bpm and high HR: \>100 bpm. If values were unchanged (example: increase to \>100 bpm to increase to \>100 bpm), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%.
Time frame: Baseline (Day 1) and up to maximum 33 weeks
Population: All Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Worst Case Change From Baseline in HR | Change to normal or no change | 4 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Worst Case Change From Baseline in HR | Decrease to low | 2 Participants |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Worst Case Change From Baseline in HR | Increase to high | 3 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Worst Case Change From Baseline in HR | Change to normal or no change | 3 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Worst Case Change From Baseline in HR | Decrease to low | 1 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Worst Case Change From Baseline in HR | Increase to high | 4 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Worst Case Change From Baseline in HR | Decrease to low | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Worst Case Change From Baseline in HR | Increase to high | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Worst Case Change From Baseline in HR | Change to normal or no change | 5 Participants |
Primary
Part 2B: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings
A 12-lead ECG was obtained after the participant had rested at least 10 minutes in a semi-recumbent or supine position during the study using ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with worst case post Baseline abnormal clinical significant ECG findings are presented.
Time frame: Up to maximum 33 weeks
Population: All Treated Population. Only those participants with data available at the indicated data points were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings | 0 Participants |
Secondary
Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK3174998
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods.
Time frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days)
Population: Pharmacokinetic Population. Only those participants with data available at the indicated data points were analyzed (represented by n=X in category titles). There were not enough samples with concentrations above lower limit of quantification to allow calculation of AUC(0-tau) for 0.003mg and 0.01mg arms in Cycles 1 and 2. There was not enough PK sampling in Cycles 3,4 and 5 for all arms to allow calculation of AUC(0-tau).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK3174998 | Cycle 1, n=0,0,6,10,9,3,7,4 | 2.9362 Day*micrograms per milliliter | Geometric Coefficient of Variation 56.6 |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK3174998 | Cycle 2, n=0,0,2,7,9,2,4,3 | 2.2804 Day*micrograms per milliliter | Geometric Coefficient of Variation 102.7 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK3174998 | Cycle 1, n=0,0,6,10,9,3,7,4 | 11.272 Day*micrograms per milliliter | Geometric Coefficient of Variation 57.8 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK3174998 | Cycle 2, n=0,0,2,7,9,2,4,3 | 8.7296 Day*micrograms per milliliter | Geometric Coefficient of Variation 62.8 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK3174998 | Cycle 1, n=0,0,6,10,9,3,7,4 | 39.374 Day*micrograms per milliliter | Geometric Coefficient of Variation 17.5 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK3174998 | Cycle 2, n=0,0,2,7,9,2,4,3 | 46.093 Day*micrograms per milliliter | Geometric Coefficient of Variation 30.7 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK3174998 | Cycle 1, n=0,0,6,10,9,3,7,4 | 175.09 Day*micrograms per milliliter | Geometric Coefficient of Variation 33.2 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK3174998 | Cycle 2, n=0,0,2,7,9,2,4,3 | 255.78 Day*micrograms per milliliter | Geometric Coefficient of Variation 12.5 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK3174998 | Cycle 1, n=0,0,6,10,9,3,7,4 | 630.94 Day*micrograms per milliliter | Geometric Coefficient of Variation 23.7 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK3174998 | Cycle 2, n=0,0,2,7,9,2,4,3 | 866.23 Day*micrograms per milliliter | Geometric Coefficient of Variation 33.5 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK3174998 | Cycle 1, n=0,0,6,10,9,3,7,4 | 2129.9 Day*micrograms per milliliter | Geometric Coefficient of Variation 30.4 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK3174998 | Cycle 2, n=0,0,2,7,9,2,4,3 | 2859.4 Day*micrograms per milliliter | Geometric Coefficient of Variation 16.7 |
Secondary
Part 1: Disease Control Rate (DCR)
DCR is defined as the percentage of participants with a confirmed CR or PR at any time, plus stable disease (SD) \>=12 weeks as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter. PR: \>=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart. SD: 30% decrease in tumor burden compared with Baseline cannot be established nor 20% increase compared with nadir.
Time frame: Up to maximum 39 weeks
Population: All Treated Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Disease Control Rate (DCR) | 0 Percentage of participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Disease Control Rate (DCR) | 0 Percentage of participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Disease Control Rate (DCR) | 0 Percentage of participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Disease Control Rate (DCR) | 10 Percentage of participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Disease Control Rate (DCR) | 20 Percentage of participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Disease Control Rate (DCR) | 0 Percentage of participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Disease Control Rate (DCR) | 14 Percentage of participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Disease Control Rate (DCR) | 75 Percentage of participants |
Secondary
Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods.
Time frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days)
Population: Pharmacokinetic Population. Only those participants with data available at the indicated data points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 1, n=1,1,8,10,10,4,7,4 | 0.04440 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 2, n=1,1,8,10,10,4,6,4 | 0.04280 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 3, n=0,1,6,7,9,3,5,3 | 0.2671 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 2, n=1,1,8,10,10,4,6,4 | 0.1737 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 1, n=1,1,8,10,10,4,7,4 | 0.1814 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 1, n=0,0,1,4,10,3,7,4 | 0.02450 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 4, n=0,0,3,4,7,4,4,2 | 0.3112 Micrograms per milliliter | Geometric Coefficient of Variation 395 |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 2, n=1,1,8,10,10,4,6,4 | 0.5816 Micrograms per milliliter | Geometric Coefficient of Variation 40.9 |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 1, n=1,1,8,10,10,4,7,4 | 0.8408 Micrograms per milliliter | Geometric Coefficient of Variation 43.1 |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 3, n=0,0,1,2,7,3,4,3 | 0.1162 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 2, n=0,0,1,3,9,3,5,3 | 0.01570 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 3, n=0,1,6,7,9,3,5,3 | 0.2532 Micrograms per milliliter | Geometric Coefficient of Variation 369.2 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 1, n=0,0,1,4,10,3,7,4 | 0.04138 Micrograms per milliliter | Geometric Coefficient of Variation 139.4 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 3, n=0,1,6,7,9,3,5,3 | 1.355 Micrograms per milliliter | Geometric Coefficient of Variation 206.1 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 2, n=0,0,1,3,9,3,5,3 | 0.05811 Micrograms per milliliter | Geometric Coefficient of Variation 50 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 1, n=1,1,8,10,10,4,7,4 | 2.808 Micrograms per milliliter | Geometric Coefficient of Variation 35.5 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 3, n=0,0,1,2,7,3,4,3 | 0.03436 Micrograms per milliliter | Geometric Coefficient of Variation 39.2 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 4, n=0,0,0,2,3,2,2,3 | 0.04153 Micrograms per milliliter | Geometric Coefficient of Variation 75 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 4, n=0,0,3,4,7,4,4,2 | 0.5338 Micrograms per milliliter | Geometric Coefficient of Variation 1632.6 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 5, n=0,0,0,3,3,2,2,3 | 1.024 Micrograms per milliliter | Geometric Coefficient of Variation 264.9 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 2, n=1,1,8,10,10,4,6,4 | 2.539 Micrograms per milliliter | Geometric Coefficient of Variation 20.4 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 4, n=0,0,0,2,3,2,2,3 | 1.053 Micrograms per milliliter | Geometric Coefficient of Variation 81.8 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 1, n=1,1,8,10,10,4,7,4 | 6.002 Micrograms per milliliter | Geometric Coefficient of Variation 24 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 2, n=1,1,8,10,10,4,6,4 | 7.096 Micrograms per milliliter | Geometric Coefficient of Variation 25.8 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 3, n=0,1,6,7,9,3,5,3 | 7.011 Micrograms per milliliter | Geometric Coefficient of Variation 35.7 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 4, n=0,0,3,4,7,4,4,2 | 7.573 Micrograms per milliliter | Geometric Coefficient of Variation 34.5 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 5, n=0,0,0,3,3,2,2,3 | 9.292 Micrograms per milliliter | Geometric Coefficient of Variation 20.9 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 1, n=0,0,1,4,10,3,7,4 | 0.5417 Micrograms per milliliter | Geometric Coefficient of Variation 62.6 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 2, n=0,0,1,3,9,3,5,3 | 0.6702 Micrograms per milliliter | Geometric Coefficient of Variation 86.3 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 3, n=0,0,1,2,7,3,4,3 | 0.9979 Micrograms per milliliter | Geometric Coefficient of Variation 52.7 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 5, n=0,0,0,0,2,2,1,2 | 1.313 Micrograms per milliliter | Geometric Coefficient of Variation 17.1 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 5, n=0,0,0,3,3,2,2,3 | 32.82 Micrograms per milliliter | Geometric Coefficient of Variation 1.4 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 3, n=0,1,6,7,9,3,5,3 | 30.60 Micrograms per milliliter | Geometric Coefficient of Variation 2.1 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 1, n=0,0,1,4,10,3,7,4 | 3.626 Micrograms per milliliter | Geometric Coefficient of Variation 35.4 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 5, n=0,0,0,0,2,2,1,2 | 8.486 Micrograms per milliliter | Geometric Coefficient of Variation 7 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 2, n=0,0,1,3,9,3,5,3 | 6.353 Micrograms per milliliter | Geometric Coefficient of Variation 12.3 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 2, n=1,1,8,10,10,4,6,4 | 24.13 Micrograms per milliliter | Geometric Coefficient of Variation 49.4 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 3, n=0,0,1,2,7,3,4,3 | 7.633 Micrograms per milliliter | Geometric Coefficient of Variation 10.9 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 1, n=1,1,8,10,10,4,7,4 | 22.70 Micrograms per milliliter | Geometric Coefficient of Variation 26 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 4, n=0,0,0,2,3,2,2,3 | 8.504 Micrograms per milliliter | Geometric Coefficient of Variation 7.9 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 4, n=0,0,3,4,7,4,4,2 | 8.117 Micrograms per milliliter | Geometric Coefficient of Variation 2535.5 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 2, n=0,0,1,3,9,3,5,3 | 19.92 Micrograms per milliliter | Geometric Coefficient of Variation 51.3 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 5, n=0,0,0,3,3,2,2,3 | 81.35 Micrograms per milliliter | Geometric Coefficient of Variation 23 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 4, n=0,0,0,2,3,2,2,3 | 22.52 Micrograms per milliliter | Geometric Coefficient of Variation 14.2 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 3, n=0,1,6,7,9,3,5,3 | 93.67 Micrograms per milliliter | Geometric Coefficient of Variation 23.7 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 1, n=1,1,8,10,10,4,7,4 | 75.81 Micrograms per milliliter | Geometric Coefficient of Variation 22.9 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 5, n=0,0,0,0,2,2,1,2 | 19.05 Micrograms per milliliter | — |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 4, n=0,0,3,4,7,4,4,2 | 97.02 Micrograms per milliliter | Geometric Coefficient of Variation 19.7 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 1, n=0,0,1,4,10,3,7,4 | 14.73 Micrograms per milliliter | Geometric Coefficient of Variation 26.9 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 3, n=0,0,1,2,7,3,4,3 | 22.57 Micrograms per milliliter | Geometric Coefficient of Variation 40.3 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 2, n=1,1,8,10,10,4,6,4 | 90.26 Micrograms per milliliter | Geometric Coefficient of Variation 21.9 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 2, n=1,1,8,10,10,4,6,4 | 320.2 Micrograms per milliliter | Geometric Coefficient of Variation 12.1 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 3, n=0,1,6,7,9,3,5,3 | 302.9 Micrograms per milliliter | Geometric Coefficient of Variation 1.2 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 2, n=0,0,1,3,9,3,5,3 | 79.63 Micrograms per milliliter | Geometric Coefficient of Variation 36 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 4, n=0,0,0,2,3,2,2,3 | 78.37 Micrograms per milliliter | Geometric Coefficient of Variation 45.9 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 1, n=1,1,8,10,10,4,7,4 | 276.4 Micrograms per milliliter | Geometric Coefficient of Variation 10.7 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 3, n=0,0,1,2,7,3,4,3 | 72.89 Micrograms per milliliter | Geometric Coefficient of Variation 41.5 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 5, n=0,0,0,3,3,2,2,3 | 294.5 Micrograms per milliliter | Geometric Coefficient of Variation 5.5 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 5, n=0,0,0,0,2,2,1,2 | 94.01 Micrograms per milliliter | Geometric Coefficient of Variation 12.2 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmax, Cycle 4, n=0,0,3,4,7,4,4,2 | 309.3 Micrograms per milliliter | Geometric Coefficient of Variation 19.9 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 | Cmin, Cycle 1, n=0,0,1,4,10,3,7,4 | 56.29 Micrograms per milliliter | Geometric Coefficient of Variation 34.8 |
Secondary
Part 1: Number of Participants With Positive Antidrug Antibodies (ADAs) Against GSK3174998
Serum samples were collected for the determination of anti-GSK3174998 antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. The presence of treatment emergent ADA was determined using a GSK3174998 bridging style ADA assay with a bio-analytically determined cut-point determined during assay validation. Samples taken after dosing with GSK3174998 that had a value at or above the cut-point was considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Number of participants with confirmed positive anti-GSK3174998 antibodies results at any visit during the study have been presented.
Time frame: Up to maximum 39 weeks
Population: All Treated Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Number of Participants With Positive Antidrug Antibodies (ADAs) Against GSK3174998 | 0 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Number of Participants With Positive Antidrug Antibodies (ADAs) Against GSK3174998 | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Number of Participants With Positive Antidrug Antibodies (ADAs) Against GSK3174998 | 6 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Number of Participants With Positive Antidrug Antibodies (ADAs) Against GSK3174998 | 7 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Number of Participants With Positive Antidrug Antibodies (ADAs) Against GSK3174998 | 4 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Number of Participants With Positive Antidrug Antibodies (ADAs) Against GSK3174998 | 2 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Number of Participants With Positive Antidrug Antibodies (ADAs) Against GSK3174998 | 2 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Number of Participants With Positive Antidrug Antibodies (ADAs) Against GSK3174998 | 0 Participants |
Secondary
Part 1: Objective Response Rate (ORR)
ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or a partial response (PR) as the Best Overall Response (BOR), as assessed by the investigator per Response Evaluation Criteria In Solid Tumors (RECIST) Version (v) 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter. PR: \>=30 percent (%) decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart.
Time frame: Up to maximum 39 weeks
Population: All Treated Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Objective Response Rate (ORR) | 0 Percentage of participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Objective Response Rate (ORR) | 0 Percentage of participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Objective Response Rate (ORR) | 0 Percentage of participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Objective Response Rate (ORR) | 0 Percentage of participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Objective Response Rate (ORR) | 0 Percentage of participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Objective Response Rate (ORR) | 0 Percentage of participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Objective Response Rate (ORR) | 0 Percentage of participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Objective Response Rate (ORR) | 0 Percentage of participants |
Secondary
Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points
Blood samples for pharmacokinetic (PK) analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion (EOI); anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion.
Time frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion
Population: Pharmacokinetic Population consisted of all participants from the All Treated Population for whom a PK sample was obtained and analyzed. Only those participants with data available at the indicated data points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 1, predose, n=1,1,8,10,10,4,7,4 | 0.000 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 24hour after EOI, n=1,0,6,9,9,4,7,4 | 0.012 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 24hour after EOI, n=1,1,6,10,9,4,7,4 | 0.000 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 14, n=1,1,8,9,10,3,7,4 | 0.000 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 4hour after EOI, n=1,1,8,10,9,4,7,4 | 0.021 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 22, predose, n=1,1,8,10,10,4,7,4 | 0.000 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 30minutes after EOI, n=1,1,8,10,10,4,7,4 | 0.043 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 4hour after EOI, n=1,1,8,10,9,4,7,4 | 0.038 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 8, n=1,1,8,10,10,3,7,4 | 0.000 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.003 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 30minutes after EOI, n=1,1,8,10,10,4,7,4 | 0.044 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 4hour after EOI, n=1,1,8,10,9,4,7,4 | 0.149 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 30minutes after EOI, n=1,1,8,10,10,4,7,4 | 0.174 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 1, predose, n=1,1,8,10,10,4,7,4 | 0.000 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 22, predose, n=1,1,8,10,10,4,7,4 | 0.000 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 36, n=0,1,7,9,9,4,6,4 | 0.000 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 4hour after EOI, n=1,1,8,10,9,4,7,4 | 0.140 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 29, n=0,1,8,10,10,4,7,4 | 0.000 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 64, predose, n=0,1,5,5,7,4,4,3 | 0.000 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 24hour after EOI, n=1,1,6,10,9,4,7,4 | 0.083 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day43, 30minutes after EOI, n=0,1,6,7,9,3,5,3 | 0.267 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 30minutes after EOI, n=1,1,8,10,10,4,7,4 | 0.181 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 8, n=1,1,8,10,10,3,7,4 | 0.000 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 43, predose, n=0,1,6,8,9,4,5,3 | 0.000 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 14, n=1,1,8,9,10,3,7,4 | 0.000 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 36, n=0,1,7,9,9,4,6,4 | 0.013 Micrograms per milliliter | Standard Deviation 0.0313 |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 14, n=1,1,8,9,10,3,7,4 | 0.022 Micrograms per milliliter | Standard Deviation 0.0412 |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 24hour after EOI, n=1,1,6,10,9,4,7,4 | 0.564 Micrograms per milliliter | Standard Deviation 0.2508 |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 22, predose, n=1,1,8,10,10,4,7,4 | 0.003 Micrograms per milliliter | Standard Deviation 0.0087 |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 30minutes after EOI, n=1,1,8,10,10,4,7,4 | 0.619 Micrograms per milliliter | Standard Deviation 0.2229 |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 24hour after EOI, n=1,0,6,9,9,4,7,4 | 0.319 Micrograms per milliliter | Standard Deviation 0.1676 |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day64, 30minutes after EOI, n=0,0,5,5,7,4,4,2 | 0.339 Micrograms per milliliter | Standard Deviation 0.4499 |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, predose, n=0,0,1,1,2,2,1,2 | 0.000 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 85, predose, n=0,0,1,4,3,2,2,3 | 0.000 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 1, predose, n=1,1,8,10,10,4,7,4 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 30minutes after EOI, n=1,1,8,10,10,4,7,4 | 0.893 Micrograms per milliliter | Standard Deviation 0.3505 |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day85, 30minutes after EOI, n=0,0,1,4,3,2,2,3 | 0.000 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 8, n=1,1,8,10,10,3,7,4 | 0.122 Micrograms per milliliter | Standard Deviation 0.0926 |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 4hour after EOI, n=1,1,8,10,9,4,7,4 | 0.809 Micrograms per milliliter | Standard Deviation 0.3205 |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day43, 30minutes after EOI, n=0,1,6,7,9,3,5,3 | 0.547 Micrograms per milliliter | Standard Deviation 0.5929 |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 29, n=0,1,8,10,10,4,7,4 | 0.037 Micrograms per milliliter | Standard Deviation 0.0663 |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 43, predose, n=0,1,6,8,9,4,5,3 | 0.003 Micrograms per milliliter | Standard Deviation 0.0064 |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 4hour after EOI, n=1,1,8,10,9,4,7,4 | 0.523 Micrograms per milliliter | Standard Deviation 0.1963 |
| Part 1: GSK3174998 0.03 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 64, predose, n=0,1,5,5,7,4,4,3 | 0.023 Micrograms per milliliter | Standard Deviation 0.052 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day64, 30minutes after EOI, n=0,0,5,5,7,4,4,2 | 1.154 Micrograms per milliliter | Standard Deviation 1.2985 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 85, predose, n=0,0,1,4,3,2,2,3 | 0.023 Micrograms per milliliter | Standard Deviation 0.0315 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 64, predose, n=0,1,5,5,7,4,4,3 | 0.014 Micrograms per milliliter | Standard Deviation 0.0206 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 4hour after EOI, n=1,1,8,10,9,4,7,4 | 2.668 Micrograms per milliliter | Standard Deviation 1.0513 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 1, predose, n=1,1,8,10,10,4,7,4 | 0.001 Micrograms per milliliter | Standard Deviation 0.0033 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, 30minutes after EOI, n=0,0,0,1,3,2,1,2 | 1.591 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 24hour after EOI, n=1,1,6,10,9,4,7,4 | 2.080 Micrograms per milliliter | Standard Deviation 0.9446 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 8, n=1,1,8,10,10,3,7,4 | 0.678 Micrograms per milliliter | Standard Deviation 0.4251 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 14, n=1,1,8,9,10,3,7,4 | 0.190 Micrograms per milliliter | Standard Deviation 0.1577 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, predose, n=0,0,1,1,2,2,1,2 | 0.000 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 22, predose, n=1,1,8,10,10,4,7,4 | 0.026 Micrograms per milliliter | Standard Deviation 0.0529 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 30minutes after EOI, n=1,1,8,10,10,4,7,4 | 2.579 Micrograms per milliliter | Standard Deviation 0.4762 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 4hour after EOI, n=1,1,8,10,9,4,7,4 | 2.301 Micrograms per milliliter | Standard Deviation 0.4088 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 24hour after EOI, n=1,0,6,9,9,4,7,4 | 1.711 Micrograms per milliliter | Standard Deviation 0.4435 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day85, 30minutes after EOI, n=0,0,1,4,3,2,2,3 | 1.246 Micrograms per milliliter | Standard Deviation 1.3975 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 29, n=0,1,8,10,10,4,7,4 | 0.380 Micrograms per milliliter | Standard Deviation 0.2882 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 36, n=0,1,7,9,9,4,6,4 | 0.115 Micrograms per milliliter | Standard Deviation 0.1114 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 30minutes after EOI, n=1,1,8,10,10,4,7,4 | 2.958 Micrograms per milliliter | Standard Deviation 1.1359 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 43, predose, n=0,1,6,8,9,4,5,3 | 0.023 Micrograms per milliliter | Standard Deviation 0.0355 |
| Part 1: GSK3174998 0.1 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day43, 30minutes after EOI, n=0,1,6,7,9,3,5,3 | 2.130 Micrograms per milliliter | Standard Deviation 1.4403 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 8, n=1,1,8,10,10,3,7,4 | 1.932 Micrograms per milliliter | Standard Deviation 0.3732 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, 30minutes after EOI, n=0,0,0,1,3,2,1,2 | 8.377 Micrograms per milliliter | Standard Deviation 0.327 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 43, predose, n=0,1,6,8,9,4,5,3 | 0.832 Micrograms per milliliter | Standard Deviation 0.5269 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day64, 30minutes after EOI, n=0,0,5,5,7,4,4,2 | 7.952 Micrograms per milliliter | Standard Deviation 2.7538 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day43, 30minutes after EOI, n=0,1,6,7,9,3,5,3 | 7.373 Micrograms per milliliter | Standard Deviation 2.381 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 85, predose, n=0,0,1,4,3,2,2,3 | 1.227 Micrograms per milliliter | Standard Deviation 0.7462 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 36, n=0,1,7,9,9,4,6,4 | 1.227 Micrograms per milliliter | Standard Deviation 0.4101 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 24hour after EOI, n=1,0,6,9,9,4,7,4 | 4.933 Micrograms per milliliter | Standard Deviation 0.8727 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 4hour after EOI, n=1,1,8,10,9,4,7,4 | 6.519 Micrograms per milliliter | Standard Deviation 1.5717 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 24hour after EOI, n=1,1,6,10,9,4,7,4 | 4.954 Micrograms per milliliter | Standard Deviation 1.26 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day85, 30minutes after EOI, n=0,0,1,4,3,2,2,3 | 9.421 Micrograms per milliliter | Standard Deviation 1.8598 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 1, predose, n=1,1,8,10,10,4,7,4 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 22, predose, n=1,1,8,10,10,4,7,4 | 0.605 Micrograms per milliliter | Standard Deviation 0.2412 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 4hour after EOI, n=1,1,8,10,9,4,7,4 | 5.615 Micrograms per milliliter | Standard Deviation 1.3647 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 14, n=1,1,8,9,10,3,7,4 | 1.205 Micrograms per milliliter | Standard Deviation 0.2799 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, predose, n=0,0,1,1,2,2,1,2 | 1.323 Micrograms per milliliter | Standard Deviation 0.2234 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 64, predose, n=0,1,5,5,7,4,4,3 | 1.097 Micrograms per milliliter | Standard Deviation 0.4744 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 30minutes after EOI, n=1,1,8,10,10,4,7,4 | 7.256 Micrograms per milliliter | Standard Deviation 1.8199 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 30minutes after EOI, n=1,1,8,10,10,4,7,4 | 6.091 Micrograms per milliliter | Standard Deviation 1.6075 |
| Part 1: GSK3174998 0.3 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 29, n=0,1,8,10,10,4,7,4 | 2.243 Micrograms per milliliter | Standard Deviation 0.8667 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, 30minutes after EOI, n=0,0,0,1,3,2,1,2 | 33.406 Micrograms per milliliter | Standard Deviation 6.3673 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 1, predose, n=1,1,8,10,10,4,7,4 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 8, n=1,1,8,10,10,3,7,4 | 9.675 Micrograms per milliliter | Standard Deviation 2.9619 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day43, 30minutes after EOI, n=0,1,6,7,9,3,5,3 | 30.602 Micrograms per milliliter | Standard Deviation 0.6521 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 4hour after EOI, n=1,1,8,10,9,4,7,4 | 22.905 Micrograms per milliliter | Standard Deviation 9.6502 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, predose, n=0,0,1,1,2,2,1,2 | 8.497 Micrograms per milliliter | Standard Deviation 0.5922 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 24hour after EOI, n=1,1,6,10,9,4,7,4 | 17.645 Micrograms per milliliter | Standard Deviation 3.821 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 24hour after EOI, n=1,0,6,9,9,4,7,4 | 17.869 Micrograms per milliliter | Standard Deviation 9.391 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 43, predose, n=0,1,6,8,9,4,5,3 | 4.789 Micrograms per milliliter | Standard Deviation 3.2591 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 4hour after EOI, n=1,1,8,10,9,4,7,4 | 21.533 Micrograms per milliliter | Standard Deviation 5.507 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 29, n=0,1,8,10,10,4,7,4 | 8.654 Micrograms per milliliter | Standard Deviation 5.9929 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day64, 30minutes after EOI, n=0,0,5,5,7,4,4,2 | 21.941 Micrograms per milliliter | Standard Deviation 15.0801 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 36, n=0,1,7,9,9,4,6,4 | 6.428 Micrograms per milliliter | Standard Deviation 4.5933 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 30minutes after EOI, n=1,1,8,10,10,4,7,4 | 23.224 Micrograms per milliliter | Standard Deviation 5.2813 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 85, predose, n=0,0,1,4,3,2,2,3 | 8.518 Micrograms per milliliter | Standard Deviation 0.67 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 64, predose, n=0,1,5,5,7,4,4,3 | 5.747 Micrograms per milliliter | Standard Deviation 3.8915 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 22, predose, n=1,1,8,10,10,4,7,4 | 2.826 Micrograms per milliliter | Standard Deviation 2.1396 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 14, n=1,1,8,9,10,3,7,4 | 5.303 Micrograms per milliliter | Standard Deviation 1.943 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 30minutes after EOI, n=1,1,8,10,10,4,7,4 | 25.859 Micrograms per milliliter | Standard Deviation 9.2995 |
| Part 1: GSK3174998 1.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day85, 30minutes after EOI, n=0,0,1,4,3,2,2,3 | 32.824 Micrograms per milliliter | Standard Deviation 0.4611 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 22, predose, n=1,1,8,10,10,4,7,4 | 15.185 Micrograms per milliliter | Standard Deviation 4.1187 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 1, predose, n=1,1,8,10,10,4,7,4 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 30minutes after EOI, n=1,1,8,10,10,4,7,4 | 77.500 Micrograms per milliliter | Standard Deviation 17.8619 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 4hour after EOI, n=1,1,8,10,9,4,7,4 | 70.603 Micrograms per milliliter | Standard Deviation 15.1388 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 24hour after EOI, n=1,1,6,10,9,4,7,4 | 59.143 Micrograms per milliliter | Standard Deviation 12.1864 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 8, n=1,1,8,10,10,3,7,4 | 32.974 Micrograms per milliliter | Standard Deviation 8.484 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 14, n=1,1,8,9,10,3,7,4 | 21.705 Micrograms per milliliter | Standard Deviation 6.4334 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 30minutes after EOI, n=1,1,8,10,10,4,7,4 | 81.115 Micrograms per milliliter | Standard Deviation 32.5472 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 4hour after EOI, n=1,1,8,10,9,4,7,4 | 82.690 Micrograms per milliliter | Standard Deviation 18.1793 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 24hour after EOI, n=1,0,6,9,9,4,7,4 | 72.801 Micrograms per milliliter | Standard Deviation 17.5925 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 29, n=0,1,8,10,10,4,7,4 | 42.013 Micrograms per milliliter | Standard Deviation 13.3448 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 36, n=0,1,7,9,9,4,6,4 | 31.093 Micrograms per milliliter | Standard Deviation 10.5909 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 43, predose, n=0,1,6,8,9,4,5,3 | 21.658 Micrograms per milliliter | Standard Deviation 8.9413 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day43, 30minutes after EOI, n=0,1,6,7,9,3,5,3 | 95.775 Micrograms per milliliter | Standard Deviation 22.93 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 64, predose, n=0,1,5,5,7,4,4,3 | 23.922 Micrograms per milliliter | Standard Deviation 9.6447 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day64, 30minutes after EOI, n=0,0,5,5,7,4,4,2 | 98.410 Micrograms per milliliter | Standard Deviation 19.0269 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 85, predose, n=0,0,1,4,3,2,2,3 | 22.635 Micrograms per milliliter | Standard Deviation 3.1816 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day85, 30minutes after EOI, n=0,0,1,4,3,2,2,3 | 82.402 Micrograms per milliliter | Standard Deviation 18.5192 |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, predose, n=0,0,1,1,2,2,1,2 | 19.047 Micrograms per milliliter | — |
| Part 1: GSK3174998 3.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, 30minutes after EOI, n=0,0,0,1,3,2,1,2 | 79.852 Micrograms per milliliter | — |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 36, n=0,1,7,9,9,4,6,4 | 111.545 Micrograms per milliliter | Standard Deviation 22.8298 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 30minutes after EOI, n=1,1,8,10,10,4,7,4 | 277.615 Micrograms per milliliter | Standard Deviation 30.9564 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 85, predose, n=0,0,1,4,3,2,2,3 | 83.090 Micrograms per milliliter | Standard Deviation 31.8311 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 29, n=0,1,8,10,10,4,7,4 | 153.655 Micrograms per milliliter | Standard Deviation 37.5871 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 24hour after EOI, n=1,0,6,9,9,4,7,4 | 260.830 Micrograms per milliliter | Standard Deviation 44.1526 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 4hour after EOI, n=1,1,8,10,9,4,7,4 | 306.585 Micrograms per milliliter | Standard Deviation 31.7702 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 30minutes after EOI, n=1,1,8,10,10,4,7,4 | 321.132 Micrograms per milliliter | Standard Deviation 40.4375 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 1, predose, n=1,1,8,10,10,4,7,4 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day85, 30minutes after EOI, n=0,0,1,4,3,2,2,3 | 294.788 Micrograms per milliliter | Standard Deviation 15.9947 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 22, predose, n=1,1,8,10,10,4,7,4 | 58.537 Micrograms per milliliter | Standard Deviation 17.2736 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 14, n=1,1,8,9,10,3,7,4 | 80.909 Micrograms per milliliter | Standard Deviation 27.3394 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 8, n=1,1,8,10,10,3,7,4 | 108.278 Micrograms per milliliter | Standard Deviation 44.5563 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 24hour after EOI, n=1,1,6,10,9,4,7,4 | 191.862 Micrograms per milliliter | Standard Deviation 35.7293 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, 30minutes after EOI, n=0,0,0,1,3,2,1,2 | 307.222 Micrograms per milliliter | Standard Deviation 3.5048 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, predose, n=0,0,1,1,2,2,1,2 | 94.359 Micrograms per milliliter | Standard Deviation 11.4639 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 4hour after EOI, n=1,1,8,10,9,4,7,4 | 243.701 Micrograms per milliliter | Standard Deviation 42.5698 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day64, 30minutes after EOI, n=0,0,5,5,7,4,4,2 | 312.277 Micrograms per milliliter | Standard Deviation 61.0388 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 64, predose, n=0,1,5,5,7,4,4,3 | 76.602 Micrograms per milliliter | Standard Deviation 27.6046 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day43, 30minutes after EOI, n=0,1,6,7,9,3,5,3 | 302.882 Micrograms per milliliter | Standard Deviation 3.7341 |
| Part 1: GSK3174998 10.0 mg/kg | Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 43, predose, n=0,1,6,8,9,4,5,3 | 82.723 Micrograms per milliliter | Standard Deviation 26.1829 |
Secondary
Part 2A: AUC(0-tau) of GSK3174998
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods.
Time frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days)
Population: Pharmacokinetic Population. Only those participants with data available at the indicated data points were analyzed (represented by n=X in category titles). There were not enough samples with concentrations above lower limit of quantification to allow calculation of AUC(0-tau) for 0.003mg and 0.01mg arms in Cycles 1 and 2. There was not enough PK sampling in Cycles 3,4 and 5 in all arms to allow calculation of AUC(0-tau).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: AUC(0-tau) of GSK3174998 | Cycle 1, n=0,0,4,10,9,8,12,3 | 4.2333 Day*micrograms per milliliter | Geometric Coefficient of Variation 77.9 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: AUC(0-tau) of GSK3174998 | Cycle 2, n=0,0,2,6,7,8,12,1 | 4.0512 Day*micrograms per milliliter | Geometric Coefficient of Variation 64.9 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: AUC(0-tau) of GSK3174998 | Cycle 1, n=0,0,4,10,9,8,12,3 | 11.592 Day*micrograms per milliliter | Geometric Coefficient of Variation 42.4 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: AUC(0-tau) of GSK3174998 | Cycle 2, n=0,0,2,6,7,8,12,1 | 10.862 Day*micrograms per milliliter | Geometric Coefficient of Variation 44 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: AUC(0-tau) of GSK3174998 | Cycle 1, n=0,0,4,10,9,8,12,3 | 40.936 Day*micrograms per milliliter | Geometric Coefficient of Variation 34.2 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: AUC(0-tau) of GSK3174998 | Cycle 2, n=0,0,2,6,7,8,12,1 | 52.517 Day*micrograms per milliliter | Geometric Coefficient of Variation 78.9 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: AUC(0-tau) of GSK3174998 | Cycle 1, n=0,0,4,10,9,8,12,3 | 175.17 Day*micrograms per milliliter | Geometric Coefficient of Variation 32.6 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: AUC(0-tau) of GSK3174998 | Cycle 2, n=0,0,2,6,7,8,12,1 | 271.67 Day*micrograms per milliliter | Geometric Coefficient of Variation 30 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: AUC(0-tau) of GSK3174998 | Cycle 1, n=0,0,4,10,9,8,12,3 | 605.22 Day*micrograms per milliliter | Geometric Coefficient of Variation 29.2 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: AUC(0-tau) of GSK3174998 | Cycle 2, n=0,0,2,6,7,8,12,1 | 862.97 Day*micrograms per milliliter | Geometric Coefficient of Variation 30.8 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: AUC(0-tau) of GSK3174998 | Cycle 1, n=0,0,4,10,9,8,12,3 | 1465.8 Day*micrograms per milliliter | Geometric Coefficient of Variation 20.3 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: AUC(0-tau) of GSK3174998 | Cycle 2, n=0,0,2,6,7,8,12,1 | 2801.8 Day*micrograms per milliliter | — |
Secondary
Part 2A: AUC(0-tau) of Pembrolizumab
Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods.
Time frame: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days)
Population: Pharmacokinetic Population. Only those participants with data available at the indicated data points were analyzed. There were not enough PK sampling in Cycles 3 and 5 to allow calculation of AUC (0-tau).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: AUC(0-tau) of Pembrolizumab | 402.11 Day*micrograms per milliliter | Geometric Coefficient of Variation 43.3 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: AUC(0-tau) of Pembrolizumab | 561.35 Day*micrograms per milliliter | Geometric Coefficient of Variation 34.2 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: AUC(0-tau) of Pembrolizumab | 616.43 Day*micrograms per milliliter | Geometric Coefficient of Variation 43.7 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: AUC(0-tau) of Pembrolizumab | 581.61 Day*micrograms per milliliter | Geometric Coefficient of Variation 34.1 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: AUC(0-tau) of Pembrolizumab | 528.06 Day*micrograms per milliliter | Geometric Coefficient of Variation 33.4 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: AUC(0-tau) of Pembrolizumab | 639.86 Day*micrograms per milliliter | Geometric Coefficient of Variation 44.8 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: AUC(0-tau) of Pembrolizumab | 657.22 Day*micrograms per milliliter | Geometric Coefficient of Variation 22.5 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: AUC(0-tau) of Pembrolizumab | 703.61 Day*micrograms per milliliter | Geometric Coefficient of Variation 27.1 |
Secondary
Part 2A: Cmax and Cmin of GSK3174998
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods.
Time frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days)
Population: Pharmacokinetic Population. Only those participants with data available at the indicated data points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 2, n=3,1,9,9,12,9,12,3 | 0.07490 Micrograms per milliliter | Geometric Coefficient of Variation 43.7 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 1, n=4,5,9,10,11,9,12,4 | 0.05321 Micrograms per milliliter | Geometric Coefficient of Variation 37.3 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 4, n=1,3,1,7,4,8,10,0 | 0.06740 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 3, n=3,3,6,7,8,8,12,1 | 0.06961 Micrograms per milliliter | Geometric Coefficient of Variation 23.1 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 1, n=4,5,9,10,11,9,12,4 | 0.2505 Micrograms per milliliter | Geometric Coefficient of Variation 23.6 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 2, n=3,1,9,9,12,9,12,3 | 0.2496 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 3, n=3,3,6,7,8,8,12,1 | 0.2269 Micrograms per milliliter | Geometric Coefficient of Variation 16 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 4, n=1,3,1,7,4,8,10,0 | 0.2328 Micrograms per milliliter | Geometric Coefficient of Variation 0.2328 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 5, n=0,3,0,5,5,7,8,0 | 0.2095 Micrograms per milliliter | Geometric Coefficient of Variation 56.6 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 4, n=1,3,1,7,4,8,10,0 | 0.5677 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 1, n=4,5,9,10,11,9,12,4 | 0.6748 Micrograms per milliliter | Geometric Coefficient of Variation 95.1 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 2, n=3,1,9,9,12,9,12,3 | 0.7805 Micrograms per milliliter | Geometric Coefficient of Variation 44.6 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 3, n=3,3,6,7,8,8,12,1 | 0.5577 Micrograms per milliliter | Geometric Coefficient of Variation 31.4 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmin, Cycle 1, n=0,0,1,6,12,9,12,3 | 1.062 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmin, Cycle 2, n=0,0,0,2,8,9,12,1 | 0.2482 Micrograms per milliliter | Geometric Coefficient of Variation 5.2 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmin, Cycle 5, n=0,0,0,3,4,5,8,0 | 0.2912 Micrograms per milliliter | Geometric Coefficient of Variation 42.9 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 3, n=3,3,6,7,8,8,12,1 | 1.614 Micrograms per milliliter | Geometric Coefficient of Variation 90.5 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 1, n=4,5,9,10,11,9,12,4 | 2.446 Micrograms per milliliter | Geometric Coefficient of Variation 23.4 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 2, n=3,1,9,9,12,9,12,3 | 2.419 Micrograms per milliliter | Geometric Coefficient of Variation 17.8 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmin, Cycle 3, n=0,0,0,3,4,8,10,0 | 0.09191 Micrograms per milliliter | Geometric Coefficient of Variation 148 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 5, n=0,3,0,5,5,7,8,0 | 1.664 Micrograms per milliliter | Geometric Coefficient of Variation 161.3 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 4, n=1,3,1,7,4,8,10,0 | 1.565 Micrograms per milliliter | Geometric Coefficient of Variation 133.4 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmin, Cycle 4, n=0,0,0,3,5,7,8,0 | 0.1536 Micrograms per milliliter | Geometric Coefficient of Variation 95.4 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmin, Cycle 1, n=0,0,1,6,12,9,12,3 | 0.1120 Micrograms per milliliter | Geometric Coefficient of Variation 77.4 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmin, Cycle 1, n=0,0,1,6,12,9,12,3 | 0.5031 Micrograms per milliliter | Geometric Coefficient of Variation 90.6 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 2, n=3,1,9,9,12,9,12,3 | 7.129 Micrograms per milliliter | Geometric Coefficient of Variation 37.2 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmin, Cycle 4, n=0,0,0,3,5,7,8,0 | 0.4313 Micrograms per milliliter | Geometric Coefficient of Variation 383.9 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 5, n=0,3,0,5,5,7,8,0 | 7.427 Micrograms per milliliter | Geometric Coefficient of Variation 31.8 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 3, n=3,3,6,7,8,8,12,1 | 7.373 Micrograms per milliliter | Geometric Coefficient of Variation 29.2 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmin, Cycle 3, n=0,0,0,3,4,8,10,0 | 0.2505 Micrograms per milliliter | Geometric Coefficient of Variation 667.3 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 4, n=1,3,1,7,4,8,10,0 | 4.898 Micrograms per milliliter | Geometric Coefficient of Variation 107 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 1, n=4,5,9,10,11,9,12,4 | 6.345 Micrograms per milliliter | Geometric Coefficient of Variation 30.8 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmin, Cycle 5, n=0,0,0,3,4,5,8,0 | 0.3995 Micrograms per milliliter | Geometric Coefficient of Variation 407.8 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmin, Cycle 2, n=0,0,0,2,8,9,12,1 | 0.6783 Micrograms per milliliter | Geometric Coefficient of Variation 161.3 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmin, Cycle 2, n=0,0,0,2,8,9,12,1 | 6.887 Micrograms per milliliter | Geometric Coefficient of Variation 33.9 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 1, n=4,5,9,10,11,9,12,4 | 23.84 Micrograms per milliliter | Geometric Coefficient of Variation 18.9 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 2, n=3,1,9,9,12,9,12,3 | 29.87 Micrograms per milliliter | Geometric Coefficient of Variation 16.8 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 3, n=3,3,6,7,8,8,12,1 | 28.02 Micrograms per milliliter | Geometric Coefficient of Variation 18.4 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 4, n=1,3,1,7,4,8,10,0 | 33.06 Micrograms per milliliter | Geometric Coefficient of Variation 14.7 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 5, n=0,3,0,5,5,7,8,0 | 34.37 Micrograms per milliliter | Geometric Coefficient of Variation 21.3 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmin, Cycle 1, n=0,0,1,6,12,9,12,3 | 5.971 Micrograms per milliliter | Geometric Coefficient of Variation 77.9 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmin, Cycle 3, n=0,0,0,3,4,8,10,0 | 7.900 Micrograms per milliliter | Geometric Coefficient of Variation 38.3 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmin, Cycle 4, n=0,0,0,3,5,7,8,0 | 9.882 Micrograms per milliliter | Geometric Coefficient of Variation 31.8 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmin, Cycle 5, n=0,0,0,3,4,5,8,0 | 9.244 Micrograms per milliliter | Geometric Coefficient of Variation 59.5 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 4, n=1,3,1,7,4,8,10,0 | 96.86 Micrograms per milliliter | Geometric Coefficient of Variation 25.2 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmin, Cycle 2, n=0,0,0,2,8,9,12,1 | 22.94 Micrograms per milliliter | Geometric Coefficient of Variation 43.8 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 2, n=3,1,9,9,12,9,12,3 | 86.21 Micrograms per milliliter | Geometric Coefficient of Variation 20.4 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmin, Cycle 5, n=0,0,0,3,4,5,8,0 | 33.69 Micrograms per milliliter | Geometric Coefficient of Variation 51.6 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmin, Cycle 4, n=0,0,0,3,5,7,8,0 | 32.44 Micrograms per milliliter | Geometric Coefficient of Variation 48.4 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmin, Cycle 1, n=0,0,1,6,12,9,12,3 | 15.04 Micrograms per milliliter | Geometric Coefficient of Variation 52.1 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 5, n=0,3,0,5,5,7,8,0 | 97.28 Micrograms per milliliter | Geometric Coefficient of Variation 28.5 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 3, n=3,3,6,7,8,8,12,1 | 92.25 Micrograms per milliliter | Geometric Coefficient of Variation 23.4 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 1, n=4,5,9,10,11,9,12,4 | 71.37 Micrograms per milliliter | Geometric Coefficient of Variation 24.1 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmin, Cycle 3, n=0,0,0,3,4,8,10,0 | 30.77 Micrograms per milliliter | Geometric Coefficient of Variation 40.4 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmin, Cycle 2, n=0,0,0,2,8,9,12,1 | 74.09 Micrograms per milliliter | — |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 3, n=3,3,6,7,8,8,12,1 | 377.1 Micrograms per milliliter | — |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 2, n=3,1,9,9,12,9,12,3 | 220.0 Micrograms per milliliter | Geometric Coefficient of Variation 19.5 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmin, Cycle 1, n=0,0,1,6,12,9,12,3 | 30.32 Micrograms per milliliter | Geometric Coefficient of Variation 40.1 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Cmax and Cmin of GSK3174998 | Cmax, Cycle 1, n=4,5,9,10,11,9,12,4 | 191.3 Micrograms per milliliter | Geometric Coefficient of Variation 16 |
Secondary
Part 2A: Cmax of Pembrolizumab
Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods.
Time frame: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days)
Population: Pharmacokinetic Population. Only those participants with data available at the indicated data points were analyzed. Post-dose samples were collected in Cycle 1 only and were not collected in Cycles 3 and 5 to calculate Cmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Cmax of Pembrolizumab | 51.83 Micrograms per milliliter | Geometric Coefficient of Variation 48.5 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Cmax of Pembrolizumab | 41.00 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Cmax of Pembrolizumab | 79.00 Micrograms per milliliter | Geometric Coefficient of Variation 34.8 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Cmax of Pembrolizumab | 57.00 Micrograms per milliliter | Geometric Coefficient of Variation 52.7 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Cmax of Pembrolizumab | 60.20 Micrograms per milliliter | Geometric Coefficient of Variation 36.2 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Cmax of Pembrolizumab | 72.73 Micrograms per milliliter | Geometric Coefficient of Variation 34.2 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Cmax of Pembrolizumab | 64.66 Micrograms per milliliter | Geometric Coefficient of Variation 22 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Cmax of Pembrolizumab | 63.65 Micrograms per milliliter | Geometric Coefficient of Variation 25.1 |
Secondary
Part 2A: Cmin of Pembrolizumab
Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15; Pre-dose on Days 22; Cycle 3 (Day 64), Cycle 5 (Day 106) (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods.
Time frame: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22; Cycle 3 (Day 64), Cycle 5 (Day 106) (each dosing cycle was of 21 days)
Population: Pharmacokinetic Population. Only those participants with data available at the indicated data points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Cmin of Pembrolizumab | Cycle 3, n=3,3,2,6,5,8,10,0 | 21.71 Micrograms per milliliter | Geometric Coefficient of Variation 32.7 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Cmin of Pembrolizumab | Cycle 5, n=1,1,0,6,5,5,8,0 | 18.50 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Cmin of Pembrolizumab | Cycle 1, n=5,3,9,10,11,11,12,3 | 11.85 Micrograms per milliliter | Geometric Coefficient of Variation 26.8 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Cmin of Pembrolizumab | Cycle 3, n=3,3,2,6,5,8,10,0 | 29.40 Micrograms per milliliter | Geometric Coefficient of Variation 27.1 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Cmin of Pembrolizumab | Cycle 1, n=5,3,9,10,11,11,12,3 | 12.27 Micrograms per milliliter | Geometric Coefficient of Variation 12.6 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Cmin of Pembrolizumab | Cycle 5, n=1,1,0,6,5,5,8,0 | 28.10 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Cmin of Pembrolizumab | Cycle 3, n=3,3,2,6,5,8,10,0 | 37.27 Micrograms per milliliter | Geometric Coefficient of Variation 38.3 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Cmin of Pembrolizumab | Cycle 1, n=5,3,9,10,11,11,12,3 | 15.52 Micrograms per milliliter | Geometric Coefficient of Variation 56.6 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Cmin of Pembrolizumab | Cycle 5, n=1,1,0,6,5,5,8,0 | 37.73 Micrograms per milliliter | Geometric Coefficient of Variation 42.2 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Cmin of Pembrolizumab | Cycle 3, n=3,3,2,6,5,8,10,0 | 22.06 Micrograms per milliliter | Geometric Coefficient of Variation 85.1 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Cmin of Pembrolizumab | Cycle 1, n=5,3,9,10,11,11,12,3 | 16.70 Micrograms per milliliter | Geometric Coefficient of Variation 42.6 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Cmin of Pembrolizumab | Cycle 1, n=5,3,9,10,11,11,12,3 | 15.81 Micrograms per milliliter | Geometric Coefficient of Variation 54.5 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Cmin of Pembrolizumab | Cycle 3, n=3,3,2,6,5,8,10,0 | 29.93 Micrograms per milliliter | Geometric Coefficient of Variation 25.3 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Cmin of Pembrolizumab | Cycle 5, n=1,1,0,6,5,5,8,0 | 41.02 Micrograms per milliliter | Geometric Coefficient of Variation 57 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Cmin of Pembrolizumab | Cycle 3, n=3,3,2,6,5,8,10,0 | 34.41 Micrograms per milliliter | Geometric Coefficient of Variation 44.6 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Cmin of Pembrolizumab | Cycle 1, n=5,3,9,10,11,11,12,3 | 16.86 Micrograms per milliliter | Geometric Coefficient of Variation 52.2 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Cmin of Pembrolizumab | Cycle 5, n=1,1,0,6,5,5,8,0 | 38.13 Micrograms per milliliter | Geometric Coefficient of Variation 49.7 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Cmin of Pembrolizumab | Cycle 5, n=1,1,0,6,5,5,8,0 | 39.38 Micrograms per milliliter | Geometric Coefficient of Variation 49.6 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Cmin of Pembrolizumab | Cycle 1, n=5,3,9,10,11,11,12,3 | 17.39 Micrograms per milliliter | Geometric Coefficient of Variation 29.6 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Cmin of Pembrolizumab | Cycle 3, n=3,3,2,6,5,8,10,0 | 32.02 Micrograms per milliliter | Geometric Coefficient of Variation 33.2 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Cmin of Pembrolizumab | Cycle 1, n=5,3,9,10,11,11,12,3 | 16.78 Micrograms per milliliter | Geometric Coefficient of Variation 57.6 |
Secondary
Part 2A: Disease Control Rate (DCR)
DCR is defined as the percentage of participants with a confirmed CR or PR at any time, plus SD \>=12 weeks as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter. PR: \>=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart. SD: 30% decrease in tumor burden compared with Baseline cannot be established nor 20% increase compared with nadir.
Time frame: Up to maximum 105 weeks
Population: All Treated Population. The efficacy outputs were presented according to planned study treatment. One participant in Part 2A was planned for 0.01mg, but received 0.003mg at first dose in error. One participant in Part 2A was planned for 0.003mg, but received 0.3mg at first dose in error. Hence, 'N' for the 'Part 2A: GSK3174998 0.01 mg/kg+Pembrolizumab 200 mg' arm is greater than that for the Participant Flow.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Disease Control Rate (DCR) | 0 Percentage of participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Disease Control Rate (DCR) | 33 Percentage of participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Disease Control Rate (DCR) | 0 Percentage of participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Disease Control Rate (DCR) | 50 Percentage of participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Disease Control Rate (DCR) | 23 Percentage of participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Disease Control Rate (DCR) | 50 Percentage of participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Disease Control Rate (DCR) | 58 Percentage of participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Disease Control Rate (DCR) | 0 Percentage of participants |
Secondary
Part 2A: Number of Participants With Positive ADAs Against GSK3174998
Serum samples were collected for the determination of anti-GSK3174998 antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. The presence of treatment emergent ADA was determined using a GSK3174998 bridging style ADA assay with a bio-analytically determined cut-point (determined during assay validation). Samples taken after dosing with GSK3174998 that had a value at or above the cut-point was considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Number of participants with confirmed positive anti-GSK3174998 antibodies results at any visit during the study have been presented.
Time frame: Up to maximum 105 weeks
Population: All Treated Population. Only those participants with data available at the indicated data points were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Positive ADAs Against GSK3174998 | 2 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Positive ADAs Against GSK3174998 | 2 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Positive ADAs Against GSK3174998 | 6 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Positive ADAs Against GSK3174998 | 8 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Positive ADAs Against GSK3174998 | 5 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Positive ADAs Against GSK3174998 | 4 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Positive ADAs Against GSK3174998 | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Positive ADAs Against GSK3174998 | 0 Participants |
Secondary
Part 2A: Number of Participants With Positive ADAs Against Pembrolizumab
Serum samples were collected for the determination of anti-pembrolizumab antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. The presence of treatment emergent ADA was determined using a pembrolizumab bridging style ADA assay with a bio-analytically determined cut-point (determined during assay validation). Samples taken after dosing with pembrolizumab that had a value at or above the cut-point was considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Number of participants with confirmed positive anti-pembrolizumab antibodies results at any visit during the study have been presented.
Time frame: Up to maximum 105 weeks
Population: All Treated Population. Only those participants with data available at the indicated data points were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Number of Participants With Positive ADAs Against Pembrolizumab | 1 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Number of Participants With Positive ADAs Against Pembrolizumab | 0 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Number of Participants With Positive ADAs Against Pembrolizumab | 0 Participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Number of Participants With Positive ADAs Against Pembrolizumab | 0 Participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Number of Participants With Positive ADAs Against Pembrolizumab | 0 Participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Number of Participants With Positive ADAs Against Pembrolizumab | 0 Participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Number of Participants With Positive ADAs Against Pembrolizumab | 0 Participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Number of Participants With Positive ADAs Against Pembrolizumab | 0 Participants |
Secondary
Part 2A: Objective Response Rate (ORR)
ORR is defined as the percentage of participants achieving a confirmed CR or PR as the BOR, as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter. PR: \>=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart.
Time frame: Up to maximum 105 weeks
Population: All Treated Population. The efficacy outputs were presented according to planned study treatment. One participant in Part 2A was planned for 0.01mg, but received 0.003mg at first dose in error. One participant in Part 2A was planned for 0.003mg, but received 0.3mg at first dose in error. Hence, 'N' for the 'Part 2A: GSK3174998 0.01 mg/kg+Pembrolizumab 200 mg' arm is greater than that for the Participant Flow.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Objective Response Rate (ORR) | 0 Percentage of participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Objective Response Rate (ORR) | 17 Percentage of participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Objective Response Rate (ORR) | 0 Percentage of participants |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Objective Response Rate (ORR) | 25 Percentage of participants |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Objective Response Rate (ORR) | 8 Percentage of participants |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Objective Response Rate (ORR) | 8 Percentage of participants |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Objective Response Rate (ORR) | 0 Percentage of participants |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Objective Response Rate (ORR) | 0 Percentage of participants |
Secondary
Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion (EOI); anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion.
Time frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion
Population: Pharmacokinetic Population. Only those participants with data available at the indicated data points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 4hour after EOI, n=4,5,9,10,11,11,12,4 | 0.038 Micrograms per milliliter | Standard Deviation 0.0263 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 22, predose, n=3,2,10,10,12,10,12,3 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 43, predose, n=3,3,7,7,8,9,12,1 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 29, n=3,1,9,10,10,10,12,1 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 30minutes after EOI, n=4,5,9,10,11,11,12,4 | 0.051 Micrograms per milliliter | Standard Deviation 0.0212 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 64, predose, n=1,3,2,6,4,8,10,0 | 0.000 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day43, 30minutes after EOI, n=3,3,7,7,8,8,12,1 | 0.071 Micrograms per milliliter | Standard Deviation 0.0156 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 4hour after EOI, n=3,2,9,10,12,9,12,3 | 0.052 Micrograms per milliliter | Standard Deviation 0.0406 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 24hour after EOI, n=4,5,9,10,11,11,12,4 | 0.010 Micrograms per milliliter | Standard Deviation 0.0125 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 24hour after EOI, n=3,2,7,7,9,10,12,3 | 0.011 Micrograms per milliliter | Standard Deviation 0.0188 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 15, n=4,4,10,10,12,11,12,4 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 36, n=3,2,8,8,8,10,11,1 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 1, predose, n=4,5,9,10,11,11,12,4 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 30minutes after EOI, n=3,2,10,10,12,9,12,3 | 0.080 Micrograms per milliliter | Standard Deviation 0.035 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day64, 30minutes after EOI, n=1,3,2,7,4,8,10,0 | 0.067 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 8, n=4,5,10,11,14,11,12,4 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 85, predose, n=0,3,0,5,5,7,8,0 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 4hour after EOI, n=3,2,9,10,12,9,12,3 | 0.682 Micrograms per milliliter | Standard Deviation 0.6743 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 30minutes after EOI, n=3,2,10,10,12,9,12,3 | 0.879 Micrograms per milliliter | Standard Deviation 0.8898 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 30minutes after EOI, n=4,5,9,10,11,11,12,4 | 0.235 Micrograms per milliliter | Standard Deviation 0.0971 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day64, 30minutes after EOI, n=1,3,2,7,4,8,10,0 | 0.245 Micrograms per milliliter | Standard Deviation 0.0932 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 4hour after EOI, n=4,5,9,10,11,11,12,4 | 0.215 Micrograms per milliliter | Standard Deviation 0.0396 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 1, predose, n=4,5,9,10,11,11,12,4 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 64, predose, n=1,3,2,6,4,8,10,0 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day43, 30minutes after EOI, n=3,3,7,7,8,8,12,1 | 0.229 Micrograms per milliliter | Standard Deviation 0.0379 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 24hour after EOI, n=4,5,9,10,11,11,12,4 | 0.112 Micrograms per milliliter | Standard Deviation 0.0599 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, 30minutes after EOI, n=0,1,0,5,4,5,8,0 | 0.269 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 43, predose, n=3,3,7,7,8,9,12,1 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 8, n=4,5,10,11,14,11,12,4 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, predose, n=0,1,0,5,5,5,8,0 | 0.000 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 36, n=3,2,8,8,8,10,11,1 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 15, n=4,4,10,10,12,11,12,4 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day85, 30minutes after EOI, n=0,3,0,5,5,7,8,0 | 0.228 Micrograms per milliliter | Standard Deviation 0.0996 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 29, n=3,1,9,10,10,10,12,1 | 0.045 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 22, predose, n=3,2,10,10,12,10,12,3 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 24hour after EOI, n=3,2,7,7,9,10,12,3 | 0.365 Micrograms per milliliter | Standard Deviation 0.3729 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day64, 30minutes after EOI, n=1,3,2,7,4,8,10,0 | 0.284 Micrograms per milliliter | Standard Deviation 0.4014 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 36, n=3,2,8,8,8,10,11,1 | 0.019 Micrograms per milliliter | Standard Deviation 0.0404 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 30minutes after EOI, n=3,2,10,10,12,9,12,3 | 0.754 Micrograms per milliliter | Standard Deviation 0.4533 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 1, predose, n=4,5,9,10,11,11,12,4 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 30minutes after EOI, n=4,5,9,10,11,11,12,4 | 0.833 Micrograms per milliliter | Standard Deviation 0.5313 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 24hour after EOI, n=3,2,7,7,9,10,12,3 | 0.628 Micrograms per milliliter | Standard Deviation 0.3755 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 24hour after EOI, n=4,5,9,10,11,11,12,4 | 0.578 Micrograms per milliliter | Standard Deviation 0.4049 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 15, n=4,4,10,10,12,11,12,4 | 0.257 Micrograms per milliliter | Standard Deviation 0.7547 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day43, 30minutes after EOI, n=3,3,7,7,8,8,12,1 | 0.496 Micrograms per milliliter | Standard Deviation 0.2657 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 43, predose, n=3,3,7,7,8,9,12,1 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 4hour after EOI, n=3,2,9,10,12,9,12,3 | 0.704 Micrograms per milliliter | Standard Deviation 0.4011 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 4hour after EOI, n=4,5,9,10,11,11,12,4 | 0.762 Micrograms per milliliter | Standard Deviation 0.473 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 64, predose, n=1,3,2,6,4,8,10,0 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 29, n=3,1,9,10,10,10,12,1 | 0.134 Micrograms per milliliter | Standard Deviation 0.241 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 8, n=4,5,10,11,14,11,12,4 | 0.428 Micrograms per milliliter | Standard Deviation 0.9836 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 22, predose, n=3,2,10,10,12,10,12,3 | 0.106 Micrograms per milliliter | Standard Deviation 0.3359 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 36, n=3,2,8,8,8,10,11,1 | 0.243 Micrograms per milliliter | Standard Deviation 0.2081 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 1, predose, n=4,5,9,10,11,11,12,4 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 30minutes after EOI, n=4,5,9,10,11,11,12,4 | 2.088 Micrograms per milliliter | Standard Deviation 0.8049 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 4hour after EOI, n=4,5,9,10,11,11,12,4 | 2.160 Micrograms per milliliter | Standard Deviation 1.0232 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 24hour after EOI, n=4,5,9,10,11,11,12,4 | 1.644 Micrograms per milliliter | Standard Deviation 0.7086 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 8, n=4,5,10,11,14,11,12,4 | 0.592 Micrograms per milliliter | Standard Deviation 0.3233 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 15, n=4,4,10,10,12,11,12,4 | 0.200 Micrograms per milliliter | Standard Deviation 0.1821 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 22, predose, n=3,2,10,10,12,10,12,3 | 0.080 Micrograms per milliliter | Standard Deviation 0.088 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 30minutes after EOI, n=3,2,10,10,12,9,12,3 | 2.343 Micrograms per milliliter | Standard Deviation 0.5196 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 4hour after EOI, n=3,2,9,10,12,9,12,3 | 2.203 Micrograms per milliliter | Standard Deviation 0.4515 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 24hour after EOI, n=3,2,7,7,9,10,12,3 | 1.702 Micrograms per milliliter | Standard Deviation 0.3438 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 29, n=3,1,9,10,10,10,12,1 | 0.607 Micrograms per milliliter | Standard Deviation 0.3352 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 43, predose, n=3,3,7,7,8,9,12,1 | 0.071 Micrograms per milliliter | Standard Deviation 0.1213 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day43, 30minutes after EOI, n=3,3,7,7,8,8,12,1 | 1.922 Micrograms per milliliter | Standard Deviation 0.8919 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 64, predose, n=1,3,2,6,4,8,10,0 | 0.067 Micrograms per milliliter | Standard Deviation 0.1145 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day64, 30minutes after EOI, n=1,3,2,7,4,8,10,0 | 2.152 Micrograms per milliliter | Standard Deviation 1.389 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 85, predose, n=0,3,0,5,5,7,8,0 | 0.115 Micrograms per milliliter | Standard Deviation 0.1528 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day85, 30minutes after EOI, n=0,3,0,5,5,7,8,0 | 2.275 Micrograms per milliliter | Standard Deviation 1.2464 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, predose, n=0,1,0,5,5,5,8,0 | 0.184 Micrograms per milliliter | Standard Deviation 0.1858 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, 30minutes after EOI, n=0,1,0,5,4,5,8,0 | 2.477 Micrograms per milliliter | Standard Deviation 0.8254 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 36, n=3,2,8,8,8,10,11,1 | 1.994 Micrograms per milliliter | Standard Deviation 1.2562 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day85, 30minutes after EOI, n=0,3,0,5,5,7,8,0 | 7.734 Micrograms per milliliter | Standard Deviation 2.5853 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 64, predose, n=1,3,2,6,4,8,10,0 | 0.706 Micrograms per milliliter | Standard Deviation 0.8655 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 4hour after EOI, n=4,5,9,10,11,11,12,4 | 5.819 Micrograms per milliliter | Standard Deviation 1.6015 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day43, 30minutes after EOI, n=3,3,7,7,8,8,12,1 | 7.639 Micrograms per milliliter | Standard Deviation 2.1641 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 24hour after EOI, n=4,5,9,10,11,11,12,4 | 5.084 Micrograms per milliliter | Standard Deviation 1.7161 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, 30minutes after EOI, n=0,1,0,5,4,5,8,0 | 8.218 Micrograms per milliliter | Standard Deviation 3.9343 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, predose, n=0,1,0,5,5,5,8,0 | 0.647 Micrograms per milliliter | Standard Deviation 0.8249 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 43, predose, n=3,3,7,7,8,9,12,1 | 0.950 Micrograms per milliliter | Standard Deviation 0.6068 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 22, predose, n=3,2,10,10,12,10,12,3 | 0.626 Micrograms per milliliter | Standard Deviation 0.3716 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 15, n=4,4,10,10,12,11,12,4 | 1.357 Micrograms per milliliter | Standard Deviation 0.7574 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 24hour after EOI, n=3,2,7,7,9,10,12,3 | 6.015 Micrograms per milliliter | Standard Deviation 2.6501 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 29, n=3,1,9,10,10,10,12,1 | 2.682 Micrograms per milliliter | Standard Deviation 1.5569 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 4hour after EOI, n=3,2,9,10,12,9,12,3 | 6.938 Micrograms per milliliter | Standard Deviation 2.6934 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 85, predose, n=0,3,0,5,5,7,8,0 | 0.938 Micrograms per milliliter | Standard Deviation 0.9332 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day64, 30minutes after EOI, n=1,3,2,7,4,8,10,0 | 6.032 Micrograms per milliliter | Standard Deviation 3.2357 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 1, predose, n=4,5,9,10,11,11,12,4 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 30minutes after EOI, n=4,5,9,10,11,11,12,4 | 6.542 Micrograms per milliliter | Standard Deviation 2.1648 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 30minutes after EOI, n=3,2,10,10,12,9,12,3 | 7.496 Micrograms per milliliter | Standard Deviation 2.7519 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 8, n=4,5,10,11,14,11,12,4 | 2.203 Micrograms per milliliter | Standard Deviation 0.7619 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 8, n=4,5,10,11,14,11,12,4 | 12.151 Micrograms per milliliter | Standard Deviation 8.538 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 1, predose, n=4,5,9,10,11,11,12,4 | 0.928 Micrograms per milliliter | Standard Deviation 3.0764 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 24hour after EOI, n=3,2,7,7,9,10,12,3 | 21.631 Micrograms per milliliter | Standard Deviation 8.6914 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 15, n=4,4,10,10,12,11,12,4 | 8.458 Micrograms per milliliter | Standard Deviation 8.3133 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, 30minutes after EOI, n=0,1,0,5,4,5,8,0 | 33.183 Micrograms per milliliter | Standard Deviation 6.7012 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 29, n=3,1,9,10,10,10,12,1 | 11.961 Micrograms per milliliter | Standard Deviation 5.5511 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 22, predose, n=3,2,10,10,12,10,12,3 | 6.912 Micrograms per milliliter | Standard Deviation 7.0973 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 36, n=3,2,8,8,8,10,11,1 | 9.146 Micrograms per milliliter | Standard Deviation 4.7873 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 24hour after EOI, n=4,5,9,10,11,11,12,4 | 19.398 Micrograms per milliliter | Standard Deviation 5.6732 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 43, predose, n=3,3,7,7,8,9,12,1 | 7.207 Micrograms per milliliter | Standard Deviation 2.1852 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, predose, n=0,1,0,5,5,5,8,0 | 10.395 Micrograms per milliliter | Standard Deviation 5.5838 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day43, 30minutes after EOI, n=3,3,7,7,8,8,12,1 | 28.433 Micrograms per milliliter | Standard Deviation 5.1446 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 4hour after EOI, n=4,5,9,10,11,11,12,4 | 23.367 Micrograms per milliliter | Standard Deviation 4.5233 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 64, predose, n=1,3,2,6,4,8,10,0 | 8.349 Micrograms per milliliter | Standard Deviation 2.7499 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 30minutes after EOI, n=4,5,9,10,11,11,12,4 | 25.623 Micrograms per milliliter | Standard Deviation 6.4576 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day64, 30minutes after EOI, n=1,3,2,7,4,8,10,0 | 33.382 Micrograms per milliliter | Standard Deviation 5.0217 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 85, predose, n=0,3,0,5,5,7,8,0 | 10.323 Micrograms per milliliter | Standard Deviation 3.5051 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day85, 30minutes after EOI, n=0,3,0,5,5,7,8,0 | 34.982 Micrograms per milliliter | Standard Deviation 6.5978 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 30minutes after EOI, n=3,2,10,10,12,9,12,3 | 30.238 Micrograms per milliliter | Standard Deviation 4.8782 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 4hour after EOI, n=3,2,9,10,12,9,12,3 | 27.273 Micrograms per milliliter | Standard Deviation 6.0059 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 15, n=4,4,10,10,12,11,12,4 | 22.050 Micrograms per milliliter | Standard Deviation 6.8631 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 22, predose, n=3,2,10,10,12,10,12,3 | 16.354 Micrograms per milliliter | Standard Deviation 5.5789 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 8, n=4,5,10,11,14,11,12,4 | 30.442 Micrograms per milliliter | Standard Deviation 8.6063 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 4hour after EOI, n=3,2,9,10,12,9,12,3 | 82.796 Micrograms per milliliter | Standard Deviation 16.8542 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 43, predose, n=3,3,7,7,8,9,12,1 | 24.578 Micrograms per milliliter | Standard Deviation 8.5351 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 36, n=3,2,8,8,8,10,11,1 | 33.671 Micrograms per milliliter | Standard Deviation 10.9055 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 24hour after EOI, n=4,5,9,10,11,11,12,4 | 55.782 Micrograms per milliliter | Standard Deviation 13.0007 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, predose, n=0,1,0,5,5,5,8,0 | 36.990 Micrograms per milliliter | Standard Deviation 16.0967 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 4hour after EOI, n=4,5,9,10,11,11,12,4 | 66.831 Micrograms per milliliter | Standard Deviation 17.5167 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 30minutes after EOI, n=3,2,10,10,12,9,12,3 | 85.882 Micrograms per milliliter | Standard Deviation 16.2709 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day85, 30minutes after EOI, n=0,3,0,5,5,7,8,0 | 100.514 Micrograms per milliliter | Standard Deviation 26.795 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day64, 30minutes after EOI, n=1,3,2,7,4,8,10,0 | 99.623 Micrograms per milliliter | Standard Deviation 25.222 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day43, 30minutes after EOI, n=3,3,7,7,8,8,12,1 | 94.463 Micrograms per milliliter | Standard Deviation 20.957 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 24hour after EOI, n=3,2,7,7,9,10,12,3 | 69.978 Micrograms per milliliter | Standard Deviation 13.9446 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 64, predose, n=1,3,2,6,4,8,10,0 | 32.716 Micrograms per milliliter | Standard Deviation 11.1159 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, 30minutes after EOI, n=0,1,0,5,4,5,8,0 | 108.103 Micrograms per milliliter | Standard Deviation 29.3324 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 29, n=3,1,9,10,10,10,12,1 | 45.527 Micrograms per milliliter | Standard Deviation 14.7008 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 30minutes after EOI, n=4,5,9,10,11,11,12,4 | 70.550 Micrograms per milliliter | Standard Deviation 16.4984 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 85, predose, n=0,3,0,5,5,7,8,0 | 35.166 Micrograms per milliliter | Standard Deviation 13.8402 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 1, predose, n=4,5,9,10,11,11,12,4 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day43, 30minutes after EOI, n=3,3,7,7,8,8,12,1 | 377.078 Micrograms per milliliter | — |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 36, n=3,2,8,8,8,10,11,1 | 106.605 Micrograms per milliliter | — |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 30minutes after EOI, n=4,5,9,10,11,11,12,4 | 193.082 Micrograms per milliliter | Standard Deviation 30.6483 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 22, predose, n=3,2,10,10,12,10,12,3 | 31.882 Micrograms per milliliter | Standard Deviation 12.4466 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 8, n=4,5,10,11,14,11,12,4 | 71.830 Micrograms per milliliter | Standard Deviation 14.1731 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 29, n=3,1,9,10,10,10,12,1 | 67.369 Micrograms per milliliter | — |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 1, predose, n=4,5,9,10,11,11,12,4 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 15, n=4,4,10,10,12,11,12,4 | 50.342 Micrograms per milliliter | Standard Deviation 12.5709 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 24hour after EOI, n=3,2,7,7,9,10,12,3 | 164.798 Micrograms per milliliter | Standard Deviation 36.7704 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 4hour after EOI, n=3,2,9,10,12,9,12,3 | 205.085 Micrograms per milliliter | Standard Deviation 26.1667 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 43, predose, n=3,3,7,7,8,9,12,1 | 74.088 Micrograms per milliliter | — |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 4hour after EOI, n=4,5,9,10,11,11,12,4 | 178.023 Micrograms per milliliter | Standard Deviation 20.6597 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 24hour after EOI, n=4,5,9,10,11,11,12,4 | 140.747 Micrograms per milliliter | Standard Deviation 9.51 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 30minutes after EOI, n=3,2,10,10,12,9,12,3 | 222.118 Micrograms per milliliter | Standard Deviation 45.7084 |
Secondary
Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points
Blood samples for PK analysis of pembrolizumab were collected on Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion (EOPI); anytime on Days 8,15; Pre-dose on Days 22, 64, 106.
Time frame: Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22, 64, 106
Population: Pharmacokinetic Population. Only those participants with data available at the indicated data points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day1, 24hour after EOPI, n=5,4,10,8,10,12,12,4 | 44.140 Micrograms per milliliter | Standard Deviation 10.705 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 64, predose, n=3,3,2,6,5,8,10,0 | 22.433 Micrograms per milliliter | Standard Deviation 6.7678 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 8, n=5,4,10,11,14,12,12,4 | 20.340 Micrograms per milliliter | Standard Deviation 6.0719 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 22, predose, n=5,3,9,10,11,11,12,3 | 12.192 Micrograms per milliliter | Standard Deviation 3.414 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 1, predose, n=5,4,7,9,10,7,12,3 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day1, 30minutes after EOPI, n=5,1,8,6,8,7,10,4 | 40.860 Micrograms per milliliter | Standard Deviation 28.897 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 106, predose, n=1,1,0,6,5,5,8,0 | 18.500 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.003 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 15, n=5,4,10,9,13,12,11,4 | 14.560 Micrograms per milliliter | Standard Deviation 4.1531 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 8, n=5,4,10,11,14,12,12,4 | 29.600 Micrograms per milliliter | Standard Deviation 8.7882 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day1, 24hour after EOPI, n=5,4,10,8,10,12,12,4 | 56.675 Micrograms per milliliter | Standard Deviation 17.3734 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day1, 30minutes after EOPI, n=5,1,8,6,8,7,10,4 | 41.000 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 64, predose, n=3,3,2,6,5,8,10,0 | 30.133 Micrograms per milliliter | Standard Deviation 8.5008 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 1, predose, n=5,4,7,9,10,7,12,3 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 22, predose, n=5,3,9,10,11,11,12,3 | 12.333 Micrograms per milliliter | Standard Deviation 1.5177 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 106, predose, n=1,1,0,6,5,5,8,0 | 28.100 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 15, n=5,4,10,9,13,12,11,4 | 21.575 Micrograms per milliliter | Standard Deviation 8.7332 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day1, 30minutes after EOPI, n=5,1,8,6,8,7,10,4 | 72.588 Micrograms per milliliter | Standard Deviation 38.0995 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 64, predose, n=3,3,2,6,5,8,10,0 | 38.550 Micrograms per milliliter | Standard Deviation 13.93 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 1, predose, n=5,4,7,9,10,7,12,3 | 4.414 Micrograms per milliliter | Standard Deviation 11.6791 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day1, 24hour after EOPI, n=5,4,10,8,10,12,12,4 | 65.230 Micrograms per milliliter | Standard Deviation 21.4209 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 8, n=5,4,10,11,14,12,12,4 | 33.850 Micrograms per milliliter | Standard Deviation 13.1268 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 15, n=5,4,10,9,13,12,11,4 | 25.020 Micrograms per milliliter | Standard Deviation 10.7905 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 22, predose, n=5,3,9,10,11,11,12,3 | 17.610 Micrograms per milliliter | Standard Deviation 9.7207 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 1, predose, n=5,4,7,9,10,7,12,3 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day1, 24hour after EOPI, n=5,4,10,8,10,12,12,4 | 50.463 Micrograms per milliliter | Standard Deviation 19.1378 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 8, n=5,4,10,11,14,12,12,4 | 27.618 Micrograms per milliliter | Standard Deviation 10.6709 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 106, predose, n=1,1,0,6,5,5,8,0 | 40.150 Micrograms per milliliter | Standard Deviation 14.0395 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 15, n=5,4,10,9,13,12,11,4 | 21.611 Micrograms per milliliter | Standard Deviation 7.3849 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day1, 30minutes after EOPI, n=5,1,8,6,8,7,10,4 | 62.983 Micrograms per milliliter | Standard Deviation 30.3605 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 64, predose, n=3,3,2,6,5,8,10,0 | 26.560 Micrograms per milliliter | Standard Deviation 14.4486 |
| Part 1: GSK3174998 0.1 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 22, predose, n=5,3,9,10,11,11,12,3 | 17.892 Micrograms per milliliter | Standard Deviation 6.6164 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 1, predose, n=5,4,7,9,10,7,12,3 | 0.404 Micrograms per milliliter | Standard Deviation 1.2776 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day1, 30minutes after EOPI, n=5,1,8,6,8,7,10,4 | 59.175 Micrograms per milliliter | Standard Deviation 24.1666 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 106, predose, n=1,1,0,6,5,5,8,0 | 45.420 Micrograms per milliliter | Standard Deviation 20.7985 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 15, n=5,4,10,9,13,12,11,4 | 21.369 Micrograms per milliliter | Standard Deviation 10.9198 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day1, 24hour after EOPI, n=5,4,10,8,10,12,12,4 | 53.810 Micrograms per milliliter | Standard Deviation 32.8301 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 22, predose, n=5,3,9,10,11,11,12,3 | 18.245 Micrograms per milliliter | Standard Deviation 12.8696 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 64, predose, n=3,3,2,6,5,8,10,0 | 30.720 Micrograms per milliliter | Standard Deviation 8.194 |
| Part 1: GSK3174998 0.3 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 8, n=5,4,10,11,14,12,12,4 | 30.757 Micrograms per milliliter | Standard Deviation 13.6721 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 8, n=5,4,10,11,14,12,12,4 | 35.600 Micrograms per milliliter | Standard Deviation 16.0615 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day1, 30minutes after EOPI, n=5,1,8,6,8,7,10,4 | 75.857 Micrograms per milliliter | Standard Deviation 21.3825 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 64, predose, n=3,3,2,6,5,8,10,0 | 37.000 Micrograms per milliliter | Standard Deviation 14.0108 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 22, predose, n=5,3,9,10,11,11,12,3 | 19.336 Micrograms per milliliter | Standard Deviation 13.4661 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 106, predose, n=1,1,0,6,5,5,8,0 | 41.400 Micrograms per milliliter | Standard Deviation 17.4579 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day1, 24hour after EOPI, n=5,4,10,8,10,12,12,4 | 54.442 Micrograms per milliliter | Standard Deviation 17.3552 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 15, n=5,4,10,9,13,12,11,4 | 26.525 Micrograms per milliliter | Standard Deviation 16.4784 |
| Part 1: GSK3174998 1.0 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 1, predose, n=5,4,7,9,10,7,12,3 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 106, predose, n=1,1,0,6,5,5,8,0 | 42.850 Micrograms per milliliter | Standard Deviation 17.0662 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 1, predose, n=5,4,7,9,10,7,12,3 | 0.008 Micrograms per milliliter | Standard Deviation 0.0284 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day1, 30minutes after EOPI, n=5,1,8,6,8,7,10,4 | 66.100 Micrograms per milliliter | Standard Deviation 15.256 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day1, 24hour after EOPI, n=5,4,10,8,10,12,12,4 | 51.842 Micrograms per milliliter | Standard Deviation 16.3551 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 8, n=5,4,10,11,14,12,12,4 | 32.792 Micrograms per milliliter | Standard Deviation 9.0537 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 15, n=5,4,10,9,13,12,11,4 | 25.773 Micrograms per milliliter | Standard Deviation 5.3967 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 22, predose, n=5,3,9,10,11,11,12,3 | 18.067 Micrograms per milliliter | Standard Deviation 5.2824 |
| Part 1: GSK3174998 3.0 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 64, predose, n=3,3,2,6,5,8,10,0 | 33.640 Micrograms per milliliter | Standard Deviation 11.8732 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 22, predose, n=5,3,9,10,11,11,12,3 | 18.567 Micrograms per milliliter | Standard Deviation 10.6679 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 15, n=5,4,10,9,13,12,11,4 | 25.175 Micrograms per milliliter | Standard Deviation 11.0852 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 8, n=5,4,10,11,14,12,12,4 | 34.025 Micrograms per milliliter | Standard Deviation 11.7196 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day1, 24hour after EOPI, n=5,4,10,8,10,12,12,4 | 48.900 Micrograms per milliliter | Standard Deviation 15.1969 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day1, 30minutes after EOPI, n=5,1,8,6,8,7,10,4 | 65.100 Micrograms per milliliter | Standard Deviation 15.6721 |
| Part 1: GSK3174998 10.0 mg/kg | Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 1, predose, n=5,4,7,9,10,7,12,3 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
Secondary
Part 2B: AUC(0-tau) of GSK3174998
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods.
Time frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days)
Population: Pharmacokinetic Population. Only those participants with data available at the indicated data points were analyzed (represented by n=X in category titles). There were not enough samples with concentrations above lower limit of quantification to allow calculation of AUC(0-tau) for 0.003mg and 0.01mg arms in Cycles 1 and 2. There was not enough PK sampling in Cycles 3,4 and 5 in all arms to allow calculation of AUC(0-tau).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: AUC(0-tau) of GSK3174998 | Cycle 1, n=7,6,4 | 38.781 Day*micrograms per milliliter | Geometric Coefficient of Variation 9.6 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: AUC(0-tau) of GSK3174998 | Cycle 2, n=7,4,2 | 39.504 Day*micrograms per milliliter | Geometric Coefficient of Variation 31.6 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: AUC(0-tau) of GSK3174998 | Cycle 1, n=7,6,4 | 38.171 Day*micrograms per milliliter | Geometric Coefficient of Variation 43.4 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: AUC(0-tau) of GSK3174998 | Cycle 2, n=7,4,2 | 41.838 Day*micrograms per milliliter | Geometric Coefficient of Variation 96.8 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: AUC(0-tau) of GSK3174998 | Cycle 1, n=7,6,4 | 46.544 Day*micrograms per milliliter | Geometric Coefficient of Variation 21.9 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: AUC(0-tau) of GSK3174998 | Cycle 2, n=7,4,2 | 33.502 Day*micrograms per milliliter | Geometric Coefficient of Variation 57 |
Secondary
Part 2B: AUC(0-tau) of Pembrolizumab
Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods.
Time frame: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days)
Population: Pharmacokinetic Population. Only those participants with data available at the indicated data points were analyzed. There were not enough PK sampling in Cycles 3 and 5 to allow calculation of AUC (0-tau).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: AUC(0-tau) of Pembrolizumab | 470.80 Day*micrograms per milliliter | Geometric Coefficient of Variation 31.5 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: AUC(0-tau) of Pembrolizumab | 546.97 Day*micrograms per milliliter | Geometric Coefficient of Variation 29.1 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: AUC(0-tau) of Pembrolizumab | 487.40 Day*micrograms per milliliter | — |
Secondary
Part 2B: Cmax and Cmin of GSK3174998
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods.
Time frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days)
Population: Pharmacokinetic Population. Only those participants with data available at the indicated data points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmax, Cycle 1, n=6,6,4 | 6.921 Micrograms per milliliter | Geometric Coefficient of Variation 19.1 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmax, Cycle 2, n=8,7,4 | 6.114 Micrograms per milliliter | Geometric Coefficient of Variation 19.3 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmax, Cycle 3, n=8,4,2 | 6.574 Micrograms per milliliter | Geometric Coefficient of Variation 17.3 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmax, Cycle 4, n=4,3,2 | 7.352 Micrograms per milliliter | Geometric Coefficient of Variation 22.5 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmax, Cycle 5, n=2,3,2 | 10.24 Micrograms per milliliter | Geometric Coefficient of Variation 2.6 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmin, Cycle 1, n=7,5,4 | 0.3781 Micrograms per milliliter | Geometric Coefficient of Variation 81.6 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmin, Cycle 2, n=7,3,2 | 0.3082 Micrograms per milliliter | Geometric Coefficient of Variation 187.9 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmin, Cycle 3, n=3,3,2 | 0.7464 Micrograms per milliliter | Geometric Coefficient of Variation 117.5 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmin, Cycle 4, n=2,3,2 | 0.6753 Micrograms per milliliter | Geometric Coefficient of Variation 207 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmin, Cycle 5, n=1,2,2 | 1.714 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmin, Cycle 4, n=2,3,2 | 0.6852 Micrograms per milliliter | Geometric Coefficient of Variation 947.6 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmax, Cycle 1, n=6,6,4 | 5.717 Micrograms per milliliter | Geometric Coefficient of Variation 17.4 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmin, Cycle 1, n=7,5,4 | 0.7925 Micrograms per milliliter | Geometric Coefficient of Variation 68.4 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmax, Cycle 5, n=2,3,2 | 8.684 Micrograms per milliliter | Geometric Coefficient of Variation 29.5 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmax, Cycle 2, n=8,7,4 | 6.139 Micrograms per milliliter | Geometric Coefficient of Variation 21.9 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmin, Cycle 5, n=1,2,2 | 0.2250 Micrograms per milliliter | Geometric Coefficient of Variation 4329.5 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmin, Cycle 3, n=3,3,2 | 0.9898 Micrograms per milliliter | Geometric Coefficient of Variation 225.3 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmax, Cycle 3, n=8,4,2 | 7.066 Micrograms per milliliter | Geometric Coefficient of Variation 27.9 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmin, Cycle 2, n=7,3,2 | 1.092 Micrograms per milliliter | Geometric Coefficient of Variation 123.1 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmax, Cycle 4, n=4,3,2 | 7.296 Micrograms per milliliter | Geometric Coefficient of Variation 28.1 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmin, Cycle 3, n=3,3,2 | 0.3280 Micrograms per milliliter | Geometric Coefficient of Variation 577.1 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmax, Cycle 4, n=4,3,2 | 8.162 Micrograms per milliliter | Geometric Coefficient of Variation 6.8 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmax, Cycle 5, n=2,3,2 | 9.160 Micrograms per milliliter | Geometric Coefficient of Variation 14.5 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmin, Cycle 1, n=7,5,4 | 0.3823 Micrograms per milliliter | Geometric Coefficient of Variation 69.5 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmin, Cycle 4, n=2,3,2 | 0.6114 Micrograms per milliliter | Geometric Coefficient of Variation 93.9 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmin, Cycle 2, n=7,3,2 | 0.2857 Micrograms per milliliter | Geometric Coefficient of Variation 552.6 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmax, Cycle 1, n=6,6,4 | 7.596 Micrograms per milliliter | Geometric Coefficient of Variation 8.7 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmin, Cycle 5, n=1,2,2 | 0.8955 Micrograms per milliliter | Geometric Coefficient of Variation 82.7 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmax, Cycle 2, n=8,7,4 | 7.398 Micrograms per milliliter | Geometric Coefficient of Variation 12.8 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Cmax and Cmin of GSK3174998 | Cmax, Cycle 3, n=8,4,2 | 6.712 Micrograms per milliliter | Geometric Coefficient of Variation 35.5 |
Secondary
Part 2B: Cmax of Pembrolizumab
Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods.
Time frame: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days)
Population: Pharmacokinetic Population. Only those participants with data available at the indicated data points were analyzed. Post-dose samples were collected in Cycle 1 only and were not collected in Cycles 3 and 5 to calculate Cmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Cmax of Pembrolizumab | 56.03 Micrograms per milliliter | Geometric Coefficient of Variation 19.6 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Cmax of Pembrolizumab | 65.32 Micrograms per milliliter | Geometric Coefficient of Variation 21.1 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Cmax of Pembrolizumab | 64.60 Micrograms per milliliter | — |
Secondary
Part 2B: Cmin of Pembrolizumab
Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15; Pre-dose on Days 22; Cycle 3 (Day 64), Cycle 5 (Day 106) (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods.
Time frame: Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22; Cycle 3 (Day 64), Cycle 5 (Day 106) (each dosing cycle was of 21 days)
Population: Pharmacokinetic Population. Only those participants with data available at the indicated data points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Cmin of Pembrolizumab | Cycle 3, n=4,3,3 | 22.78 Micrograms per milliliter | Geometric Coefficient of Variation 34.2 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Cmin of Pembrolizumab | Cycle 1, n=9,7,4 | 12.30 Micrograms per milliliter | Geometric Coefficient of Variation 45.9 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Cmin of Pembrolizumab | Cycle 5, n=2,3,3 | 22.52 Micrograms per milliliter | Geometric Coefficient of Variation 49.2 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Cmin of Pembrolizumab | Cycle 3, n=4,3,3 | 42.86 Micrograms per milliliter | Geometric Coefficient of Variation 26.9 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Cmin of Pembrolizumab | Cycle 1, n=9,7,4 | 13.88 Micrograms per milliliter | Geometric Coefficient of Variation 50.3 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Cmin of Pembrolizumab | Cycle 5, n=2,3,3 | 39.78 Micrograms per milliliter | Geometric Coefficient of Variation 61.3 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Cmin of Pembrolizumab | Cycle 1, n=9,7,4 | 18.22 Micrograms per milliliter | Geometric Coefficient of Variation 30.3 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Cmin of Pembrolizumab | Cycle 5, n=2,3,3 | 22.52 Micrograms per milliliter | Geometric Coefficient of Variation 43.1 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Cmin of Pembrolizumab | Cycle 3, n=4,3,3 | 22.28 Micrograms per milliliter | Geometric Coefficient of Variation 26.6 |
Secondary
Part 2B: Disease Control Rate (DCR)
DCR is defined as the percentage of participants with a confirmed CR or PR at any time, plus SD \>=12 weeks as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter. PR: \>=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart. SD: 30% decrease in tumor burden compared with Baseline cannot be established nor 20% increase compared with nadir.
Time frame: Up to maximum 33 weeks
Population: All Treated Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Disease Control Rate (DCR) | 11 Percentage of participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Disease Control Rate (DCR) | 0 Percentage of participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Disease Control Rate (DCR) | 60 Percentage of participants |
Secondary
Part 2B: Number of Participants With Positive ADAs Against GSK3174998
Serum samples were collected for the determination of anti-GSK3174998 antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. The presence of treatment emergent ADA was determined using a GSK3174998 bridging style ADA assay with a bio-analytically determined cut-point (determined during assay validation). Samples taken after dosing with GSK3174998 that had a value at or above the cut-point was considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Number of participants with confirmed positive anti-GSK3174998 antibodies results at any visit during the study have been presented.
Time frame: Up to maximum 33 weeks
Population: All Treated Population. Only those participants with data available at the indicated data points were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Number of Participants With Positive ADAs Against GSK3174998 | 4 Participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Number of Participants With Positive ADAs Against GSK3174998 | 1 Participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Number of Participants With Positive ADAs Against GSK3174998 | 1 Participants |
Secondary
Part 2B: Number of Participants With Positive ADAs Against Pembrolizumab
Serum samples were planned to be collected for the determination of anti-pembrolizumab antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps.
Time frame: Up to maximum 33 weeks
Population: All Treated Population. Data for this outcome measure was not collected as ADA samples were not collected in Part 2B.
Secondary
Part 2B: Objective Response Rate (ORR)
ORR is defined as the percentage of participants achieving a confirmed CR or PR as the BOR, as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter. PR: \>=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart.
Time frame: Up to maximum 33 weeks
Population: All Treated Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Objective Response Rate (ORR) | 0 Percentage of participants |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Objective Response Rate (ORR) | 0 Percentage of participants |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Objective Response Rate (ORR) | 0 Percentage of participants |
Secondary
Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion (EOI); anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion.
Time frame: Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion
Population: Pharmacokinetic Population. Only those participants with data available at the indicated data points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 30minutes after EOI, n=8,7,4 | 5.805 Micrograms per milliliter | Standard Deviation 0.8298 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 1, predose, n=7,5,3 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 64, predose, n=4,3,2 | 0.726 Micrograms per milliliter | Standard Deviation 0.7935 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 4hour after EOI, n=8,7,4 | 5.722 Micrograms per milliliter | Standard Deviation 1.5376 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 24hour after EOI, n=7,5,0 | 4.000 Micrograms per milliliter | Standard Deviation 1.7095 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day43, 30minutes after EOI, n=8,4,2 | 6.657 Micrograms per milliliter | Standard Deviation 1.106 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 24hour after EOI, n=4,2,4 | 4.531 Micrograms per milliliter | Standard Deviation 0.6357 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, 30minutes after EOI, n=2,2,1 | 9.933 Micrograms per milliliter | Standard Deviation 1.9969 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 43, predose, n=8,4,2 | 0.442 Micrograms per milliliter | Standard Deviation 0.4862 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 29, n=9,8,4 | 1.715 Micrograms per milliliter | Standard Deviation 0.8979 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 8, n=8,7,4 | 1.972 Micrograms per milliliter | Standard Deviation 0.3899 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 36, n=7,6,4 | 0.871 Micrograms per milliliter | Standard Deviation 0.7222 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, predose, n=1,2,2 | 1.714 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day85, 30minutes after EOI, n=2,3,2 | 10.245 Micrograms per milliliter | Standard Deviation 0.2669 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 15, n=8,7,4 | 0.989 Micrograms per milliliter | Standard Deviation 0.3362 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 4hour after EOI, n=7,6,4 | 5.229 Micrograms per milliliter | Standard Deviation 2.1553 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 85, predose, n=2,3,2 | 0.976 Micrograms per milliliter | Standard Deviation 0.9973 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 22, predose, n=8,7,4 | 0.401 Micrograms per milliliter | Standard Deviation 0.3015 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 30minutes after EOI, n=7,6,4 | 6.132 Micrograms per milliliter | Standard Deviation 2.6768 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day64, 30minutes after EOI, n=4,3,2 | 7.496 Micrograms per milliliter | Standard Deviation 1.7948 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day85, 30minutes after EOI, n=2,3,2 | 8.920 Micrograms per milliliter | Standard Deviation 2.4241 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 1, predose, n=7,5,3 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 30minutes after EOI, n=7,6,4 | 5.668 Micrograms per milliliter | Standard Deviation 1.1752 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 4hour after EOI, n=7,6,4 | 5.383 Micrograms per milliliter | Standard Deviation 0.6932 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 24hour after EOI, n=7,5,0 | 4.141 Micrograms per milliliter | Standard Deviation 1.0168 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 8, n=8,7,4 | 2.062 Micrograms per milliliter | Standard Deviation 0.7993 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 15, n=8,7,4 | 1.223 Micrograms per milliliter | Standard Deviation 0.5792 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 22, predose, n=8,7,4 | 0.646 Micrograms per milliliter | Standard Deviation 0.5756 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 30minutes after EOI, n=8,7,4 | 6.259 Micrograms per milliliter | Standard Deviation 1.3552 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 4hour after EOI, n=8,7,4 | 5.810 Micrograms per milliliter | Standard Deviation 1.4074 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 24hour after EOI, n=4,2,4 | 2.070 Micrograms per milliliter | Standard Deviation 0.5224 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 29, n=9,8,4 | 2.201 Micrograms per milliliter | Standard Deviation 1.4063 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 36, n=7,6,4 | 1.597 Micrograms per milliliter | Standard Deviation 1.256 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 43, predose, n=8,4,2 | 1.045 Micrograms per milliliter | Standard Deviation 1.0289 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day43, 30minutes after EOI, n=8,4,2 | 7.271 Micrograms per milliliter | Standard Deviation 2.0499 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 64, predose, n=4,3,2 | 1.520 Micrograms per milliliter | Standard Deviation 1.2083 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day64, 30minutes after EOI, n=4,3,2 | 7.480 Micrograms per milliliter | Standard Deviation 2.0226 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 85, predose, n=2,3,2 | 1.631 Micrograms per milliliter | Standard Deviation 1.5426 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, predose, n=1,2,2 | 0.800 Micrograms per milliliter | Standard Deviation 1.0858 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, 30minutes after EOI, n=2,2,1 | 6.324 Micrograms per milliliter | Standard Deviation 1.9856 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day43, 30minutes after EOI, n=8,4,2 | 6.913 Micrograms per milliliter | Standard Deviation 2.3366 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 30minutes after EOI, n=8,7,4 | 7.226 Micrograms per milliliter | Standard Deviation 0.8588 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, 30minutes after EOI, n=2,2,1 | 8.673 Micrograms per milliliter | — |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 64, predose, n=4,3,2 | 0.663 Micrograms per milliliter | Standard Deviation 0.8153 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 22, predose, n=8,7,4 | 0.444 Micrograms per milliliter | Standard Deviation 0.2856 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day106, predose, n=1,2,2 | 1.015 Micrograms per milliliter | Standard Deviation 0.675 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day64, 30minutes after EOI, n=4,3,2 | 8.172 Micrograms per milliliter | Standard Deviation 0.5517 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 15, n=8,7,4 | 1.252 Micrograms per milliliter | Standard Deviation 0.3432 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 1, predose, n=7,5,3 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 85, predose, n=2,3,2 | 0.711 Micrograms per milliliter | Standard Deviation 0.5122 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 8, n=8,7,4 | 2.501 Micrograms per milliliter | Standard Deviation 0.6042 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 29, n=9,8,4 | 2.070 Micrograms per milliliter | Standard Deviation 0.916 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 4hour after EOI, n=7,6,4 | 6.638 Micrograms per milliliter | Standard Deviation 1.2259 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 36, n=7,6,4 | 1.124 Micrograms per milliliter | Standard Deviation 0.5805 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 24hour after EOI, n=4,2,4 | 5.850 Micrograms per milliliter | Standard Deviation 1.3604 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day85, 30minutes after EOI, n=2,3,2 | 9.208 Micrograms per milliliter | Standard Deviation 1.327 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day 43, predose, n=8,4,2 | 0.570 Micrograms per milliliter | Standard Deviation 0.6971 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day22, 4hour after EOI, n=8,7,4 | 7.363 Micrograms per milliliter | Standard Deviation 1.0038 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points | Day1, 30minutes after EOI, n=7,6,4 | 7.618 Micrograms per milliliter | Standard Deviation 0.6794 |
Secondary
Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points
Blood samples for PK analysis of pembrolizumab were collected on Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15; Pre-dose on Days 22, 64, 106.
Time frame: Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22, 64, 106
Population: Pharmacokinetic Population. Only those participants with data available at the indicated data points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 1, predose, n=8,8,5 | 3.341 Micrograms per milliliter | Standard Deviation 5.7855 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day1, 30minutes after EOPI, n=8,6,3 | 58.650 Micrograms per milliliter | Standard Deviation 12.586 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day1, 24hour after EOPI, n=8,5,0 | 46.800 Micrograms per milliliter | Standard Deviation 12.7711 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 8, n=9,8,5 | 24.178 Micrograms per milliliter | Standard Deviation 10.0888 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 15, n=9,7,5 | 18.800 Micrograms per milliliter | Standard Deviation 8.8255 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 22, predose, n=9,7,4 | 13.458 Micrograms per milliliter | Standard Deviation 6.4173 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 64, predose, n=4,3,3 | 23.775 Micrograms per milliliter | Standard Deviation 8.2754 |
| Part 1: GSK3174998 0.003 mg/kg | Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 106, predose, n=2,3,3 | 23.750 Micrograms per milliliter | Standard Deviation 10.6773 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day1, 24hour after EOPI, n=8,5,0 | 49.960 Micrograms per milliliter | Standard Deviation 7.3228 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 8, n=9,8,5 | 26.125 Micrograms per milliliter | Standard Deviation 7.6333 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 15, n=9,7,5 | 19.343 Micrograms per milliliter | Standard Deviation 7.3968 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 22, predose, n=9,7,4 | 15.180 Micrograms per milliliter | Standard Deviation 6.4652 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 1, predose, n=8,8,5 | 0.000 Micrograms per milliliter | Standard Deviation 0 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day1, 30minutes after EOPI, n=8,6,3 | 66.600 Micrograms per milliliter | Standard Deviation 15.4104 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 106, predose, n=2,3,3 | 44.200 Micrograms per milliliter | Standard Deviation 24.5514 |
| Part 1: GSK3174998 0.01 mg/kg | Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 64, predose, n=4,3,3 | 43.900 Micrograms per milliliter | Standard Deviation 12.152 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day1, 30minutes after EOPI, n=8,6,3 | 68.633 Micrograms per milliliter | Standard Deviation 7.2473 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 8, n=9,8,5 | 33.800 Micrograms per milliliter | Standard Deviation 7.5931 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 64, predose, n=4,3,3 | 22.800 Micrograms per milliliter | Standard Deviation 6.0902 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 1, predose, n=8,8,5 | 11.940 Micrograms per milliliter | Standard Deviation 7.3057 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 15, n=9,7,5 | 25.280 Micrograms per milliliter | Standard Deviation 5.7712 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 106, predose, n=2,3,3 | 23.867 Micrograms per milliliter | Standard Deviation 10.1535 |
| Part 1: GSK3174998 0.03 mg/kg | Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points | Day 22, predose, n=9,7,4 | 18.775 Micrograms per milliliter | Standard Deviation 4.7479 |