Neoplasms
Conditions
Keywords
NSCLC, Feladilimab, Iplimumab
Brief summary
This study is a sub-study of the master protocol 205801 (NCT03739710). This sub study will assess the clinical activity of novel regimen (Feladilimab plus Ipilimumab) in participants with NSCLC.
Interventions
DRUGFeladilimab
Feladilimab will be administered.
DRUGIpilimumab
Ipilimumab will be administered
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
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Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants capable of giving signed informed consent/assent. * Male or female, aged 18 years or older at the time consent is obtained. Participants in Korea must be age 19 years or older at the time consent is obtained. * Participants with histologically or cytologically confirmed diagnosis of NSCLC (squamous or non-squamous) and * Participants capable of giving signed informed consent/assent. * Male or female, aged 18 years or older at the time consent is obtained. Participants in Korea must be age 19 years or older at the time consent is obtained. * Participants with histologically or cytologically confirmed diagnosis of NSCLC (squamous or non-squamous) and 1. Documented disease progression based on radiographic imaging, during or after a maximum of 2 lines of systemic treatment for locally/regionally advanced recurrent, Stage IIIb/Stage IIIc/Stage IV or metastatic disease. Two components of treatment must have been received in the same line or as separate lines of therapy: i) No more than or less than 1 line of platinum-containing chemotherapy regimen, and ii) No more than or less than 1 line of Programmed cell death ligand 1 (PD\[L\]1) monoclonal antibody (mAb) containing regimen. 2. Participants with known V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) molecular alterations must have had disease progression after receiving the locally available SoC treatment for the molecular alteration. 3. Participants who received prior anti-PD(L)1 therapy must fulfill the following requirements: i) Have achieved a CR, PR or SD and subsequently had disease progression (per RECIST 1.1 criteria) either on or after completing PD(L)1 therapy ii) Have not progressed or recurred within the first 12 weeks of PD(L)1 therapy, either clinically or per RECIST 1.1 criteria * Measurable disease, presenting with at least 1 measurable lesion per RECIST 1.1. * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1. * A tumor tissue sample obtained at any time from the initial diagnosis of NSCLC to time of study entry is mandatory. Although a fresh tumor tissue sample obtained during screening is preferred, archival tumor specimen is acceptable. * Adequate organ function as defined in the protocol. * A male participant must agree to use a highly effective contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period. * A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions apply: i) Not a woman of childbearing potential (WOCBP) or ii) A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment. * Life expectancy of at least 12 weeks.
Exclusion criteria
* Participants who received prior treatment with the following therapies (calculation is based on date of last therapy to date of first dose of study treatment): 1. Docetaxel at any time. 2. Any of the investigational agents being tested in the current study. 3. Systemic approved or investigational anticancer therapy within 30 days or 5 half-lives of the drug, whichever is shorter. At least 14 days must have elapsed between the last dose of prior anticancer agent and the first dose of study drug is administered. 4. Prior radiation therapy: permissible if at least one non-irradiated measurable lesion is available for assessment per RECIST version 1.1 or if a solitary measurable lesion was irradiated, objective progression is documented. A wash out of at least 2 weeks before start of study drug for radiation of any intended use is required. * Received greater than (\>)2 prior lines of therapy for NSCLC, including participants with BRAF molecular alternations. * Invasive malignancy or history of invasive malignancy other than disease under study within the last 2 years, except * Any other invasive malignancy for which the participant was definitively treated, has been disease-free for at least 2 years and in the opinion of the principal investigator and GlaxoSmithKline Medical Monitor will not affect the evaluation of the effects of the study treatment on the currently targeted malignancy, may be included in this clinical trial. * Curatively treated non-melanoma skin cancer or successfully treated in situ carcinoma. * Carcinomatous meningitis (regardless of clinical status) and uncontrolled or symptomatic Central nervous system (CNS) metastases. * Major surgery less than or equal to (\<=) 28 days of first dose of study treatment. * Autoimmune disease (current or history) or syndrome that required systemic treatment within the past 2 years. Replacement therapies which include physiological doses of corticosteroids for treatment of endocrinopathies (for example, adrenal insufficiency) are not considered systemic treatments. * Receiving systemic steroids (\>10 milligrams \[mg\]) oral prednisone or equivalent) or other immunosuppressive agents within 7 days prior to first dose of study treatment. * Prior allogeneic/autologous bone marrow or solid organ transplantation. * Receipt of any live vaccine within 30 days prior to first dose of study treatment. * Toxicity from previous anticancer treatment that includes: 1. Greater than or equal to (\>=) Grade 3 toxicity considered related to prior immunotherapy and that led to treatment discontinuation. 2. Toxicity related to prior treatment that has not resolved to \<= Grade 1 (except alopecia, hearing loss, endocrinopathy managed with replacement therapy, and peripheral neuropathy which must be \<= Grade 2). * History (current and past) of idiopathic pulmonary fibrosis, pneumonitis (for past- pneumonitis exclusion only if steroids were required for treatment), interstitial lung disease, or organizing pneumonia. * Recent history (within the past 6 months) of uncontrolled symptomatic ascites, pleural or pericardial effusions. * Recent history (within the past 6 months) of gastrointestinal obstruction that required surgery, acute diverticulitis, inflammatory bowel disease, or intra-abdominal abscess. * History or evidence of cardiac abnormalities within the 6 months prior to enrollment which include 1. Serious, uncontrolled cardiac arrhythmia or clinically significant electrocardiogram abnormalities including second degree (Type II) or third degree atrioventricular block. 2. Cardiomyopathy, myocardial infarction, acute coronary syndromes (including unstable angina pectoris), coronary angioplasty, stenting or bypass grafting. 3. Symptomatic pericarditis. * Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypo-albuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. * Active infection requiring systemic therapy \<=7 days prior to first dose of study treatment. * Participants with known human immunodeficiency virus infection. * Participants with history of severe hypersensitivity to mAb or hypersensitivity to any of the study treatment(s) or their excipients. * Participants requiring ongoing therapy with a medication that is a strong inhibitor or inducer of the cytochrome P 3A4 (CYP3A4) enzymes. * Any serious and/or unstable pre-existing medical (aside from malignancy), psychiatric disorder, or other condition that could interfere with participant's safety, obtaining informed consent, or compliance to the study procedures in the opinion of the investigator. * Pregnant or lactating female participants. * Participant who is currently participating in or has participated in a study of an investigational device within 4 weeks prior to the first dose of study treatment. * Participants with presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention. * Participants with positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention. * Participants with positive hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment. * Receipt of 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, and recombinant erythropoietin) within 14 days before the first dose of study intervention.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With AE Leading to Dose Modifications | Up to 29 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. The number of participants who experienced AE leading to dose modifications were evaluated. |
| Part 1: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to 29 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involved medical or scientific judgment or is associated with liver injury and impaired liver function. SAEs are subset of AEs. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA dictionary). |
| Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Up to 21 days | Criteria for dose-limiting toxicity (DLT) included hematologic indicators such as febrile neutropenia as defined by CTCAE v5; Grade 4 neutropenia of \>7 days in duration; Grade 4 anemia and Grade 3-4 thrombocytopenia with bleeding. Non-hematologic criteria, comprising Grade 4 toxicity; Grade 3 pneumonitis of any duration; Grade 3 toxicity that does not resolve to ≤Grade 1 or baseline within 3 days despite optimal supportive care; any Grade 2 ocular toxicity requiring systemic steroids, or any ≥ Grade 3 ocular toxicity Any other toxicity considered to be dose-limiting that occurs beyond four weeks was considered as DLT. Any other event which in the judgment of the investigator and GSK Medical Monitor is considered to be a DLT. |
| Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Baseline (Day 1) and up to 29 weeks | Blood samples were collected for evaluation of hematology parameters. The summaries of worst-case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by CTCAE v5.0. The number of participants with decreases to low from baseline, changes to normal or no changes from baseline, and increases to high values have been presented. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. |
| Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Baseline (Day 1) and up to 29 weeks | Blood samples were collected for evaluation of clinical chemistry parameters. The summaries of worst-case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The number of participants with decreases to low from baseline, changes to normal or no changes from baseline, and increases to high values have been presented. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. |
| Part 1: Number of Participants With Worst Case Change Post-baseline in Urinalysis Parameters | Baseline (Day 1) and up to 29 weeks | Urine samples were collected for evaluation of urinalysis parameters using dipstick method. The dipstick test gave results in a semi-quantitative manner. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. The summaries of worst-case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by CTCAE v5.0. The number of participants with 'Any increase', or 'no changes/decreased' values have been presented. |
| Part 1: Change From Baseline in Potential of Hydrogen (pH) of Urine | Baseline (Day 1), week 4, week 7, week 10, week 13 and week 29 (Treatment Discontinuation) | Urine samples were collected from participants to assess urine pH levels. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Changes from baseline in urine pH were reported. |
| Part 1: Change From Baseline in Specific Gravity of Urine | Baseline (Day 1), week 4, week 7, week 10, week 13 and week 29 (Treatment Discontinuation) | Urine samples were collected from participants to analyze urine specific gravity. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Changes from baseline in specific gravity of urine were reported. |
| Part 2: Overall Survival | Up to 29 weeks | OS is defined as the time from randomization until death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Number of Participants With AESI | Up to 29 weeks | Number of participants with AESI were planned to be evaluated. |
| Part 2: Number of Participants With AEs and SAEs Leading to Dose Modification | Up to 29 weeks | An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function. AEs and SAEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding system. Number of participants with AEs and SAEs leading to dose modification (delays/withdrawal) were planned to be evaluated. |
| Part 2: Number of Participants With Clinically Significant Changes in Hematology Lab Parameters | Up to 29 weeks | Blood samples were to be collected for the analysis of hematology parameters. The laboratory parameters were to be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5. Grade 1 (G1): mild; Grade 2 (G2): moderate; Grade 3 (G3): severe or medically significant. Higher grade indicates greater severity and an increase in CTCAE grade were to be defined relative to the Baseline grade. |
| Part 2: Number of Participants With Clinically Significant Changes in Clinical Chemistry Lab Parameters | Up to 29 weeks | Blood samples were to be collected for the analysis of chemistry parameters. The laboratory parameters were to be graded according to CTCAE version 5. G1: mild; G2: moderate; G3: severe or medically significant. Higher grade indicates greater severity and an increase in CTCAE grade were to be defined relative to the Baseline grade. |
| Part 1: Overall Response Rate (ORR) | Up to 29 weeks | ORR was defined as the percentage of participants who had a confirmed complete response (CR) or confirmed partial response (PR) as their best overall response (BOR) recorded from the date of randomization until disease progression or initiation of new anti-cancer therapy, whichever is earlier based on blinded independent central review (BICR) evaluation criteria in solid tumors (RECIST) version 1.1 (v1.1). CR was defined as disappearance of all target lesions. Any pathological lymph nodes must be \<10 millimeter in the short axis. PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters (e.g., percent change from baseline). |
| Part 2: Maximum Concentration (Cmax) and Minimum Concentration (Cmin) | Up to 29 weeks | Blood samples were planned to be collected for PK analysis. |
| Part 2: Number of Participants With Post-baseline Positive Anti-drug Antibodies (ADAs) Against Feladilimab | Up to 29 weeks | Serum samples were to be collected for the analysis of the presence of ADAs using validated immunoassays. |
| Part 2: Number of Participants With Post-baseline Positive Anti-drug Antibodies (ADAs) Against Iplimumab | Up to 29 weeks | Serum samples were to be collected for the analysis of the presence of ADAs using validated immunoassays. |
| Part 2: Number of Participants With Clinically Significant Changes in Vital Signs | Up to 29 weeks | Vital signs were planned to be measured after 5 minutes of rest and taken in the same position throughout the study. |
| Part 1: Disease Control Rate (DCR) | Up to 29 weeks | DCR was defined as the percentage of participants with a confirmed CR + PR at any time, plus stable disease (SD) \>=12 weeks. PR was defined as at least 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 mm. Stable Disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. |
| Part 1: Maximum Concentration (Cmax) and Minimum Concentration (Cmin) | Up to 29 weeks | Blood samples were collected for PK analysis. |
| Part 2: Milestone Survival Rate at 12 and 18 Months | At 12 and 18 months | Milestone survival rate is the proportion of participants who are alive at a specific, predefined point in time after a certain event or diagnosis post treatment. |
| Part 2: Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD) Based on RECIST 1.1 | Up to 29 weeks | Complete Response \[CR\], Partial Response \[PR\], stable disease \[SD\], and progressive disease (PD) as assessed by the investigator per IMWG. CR defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 mm; PR was defined as at least 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters; Stable Disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started. |
| Part 2: Number of Participants With iRECIST Complete Response (iCR), iRECIST Partial Response (iPR), iRECIST Stable Disease (iSD), iRECIST Confirmed Progressive Disease (iCPD), and iRECIST Unconfirmed Progressive Disease (iUPD) | Up to 29 weeks | Modified RECIST 1.1 for immune-based therapeutics (iRECIST) is based on RECIST v 1.1 but adapted to account for the unique tumor response seen with immunotherapeutic drugs. iRECIST was to be used to assess tumor response and progression and make treatment decisions. iCR: disappearance of all target lesions; iPR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g. percent change from baseline). iCPD: either 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; iSD: stable disease in the absence of CR or PD and iUPD: unconfirmed progressive disease when PD is unconfirmed. |
| Part 2: Number of Participants With PFS, ORR, DOR, and DCR | Up to 29 weeks | PFS defined as time from the date of randomization to the date of disease progression or death, whichever will occurs earlier, per RECIST criteria. ORR defined as the percentage of participants with a confirmed CR or PR at any time per RECIST criteria. DOR defined as the time from first documented evidence of CR or PR until disease progression or death, per RECIST criteria. DCR was defined as the percentage of participants with a confirmed CR + PR at any time, plus stable disease (SD) \>=12 weeks. |
| Part 2: Number of Participants With iPFS, iORR, and iDOR | Up to 29 weeks | iPFS defined as time from the date of randomization to the date of disease progression or death, whichever will occurs earlier, per iRECIST criteria. iORR defined as the percentage of participants with a confirmed iCR or iPR at any time per iRECIST criteria. iDOR defined as the time from first documented evidence of CR or PR until disease progression or death, per iRECIST criteria. |
| Part 2: Number of Participants With AEs and SAEs | Up to 29 weeks | An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function. AEs and SAEs were planned to be coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding system. |
Countries
Canada, France, United States
Participant flow
Recruitment details
This is a sub-study of the master study NCT03739710. This sub study was terminated due to low enrolment of participants. The study was planned to include two phases - Part 1 and Part 2. No participants from this sub study were enrolled in part 2 as study was early terminated.
Participants by arm
| Arm | Count |
|---|---|
| Feladilimab + Ipilimumab Participants with Non-Small Cell Lung Cancer (NSCLC) received 24 milligram (mg) Feladilimab first as a 30-minute intravenous (IV) infusion followed by 1 mg/ kilogram (kg) Ipilimumab as IV infusion (started at least 30 minutes following the end of the feladilimab) once every 3 weeks (Q3W). | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 4 |
| Overall Study | Study Terminated by sponsor | 4 |
Baseline characteristics
| Characteristic | Feladilimab + Ipilimumab |
|---|---|
| Age, Customized 18 to 84 years | 8 Participants |
| Race/Ethnicity, Customized All other races | 8 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 8 |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 3 / 8 |
Outcome results
Primary
Part 1: Change From Baseline in Potential of Hydrogen (pH) of Urine
Urine samples were collected from participants to assess urine pH levels. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Changes from baseline in urine pH were reported.
Time frame: Baseline (Day 1), week 4, week 7, week 10, week 13 and week 29 (Treatment Discontinuation)
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Feladilimab + Ipilimumab | Part 1: Change From Baseline in Potential of Hydrogen (pH) of Urine | Baseline (Day 1) | 6.33 Potential of Hydrogen (pH) | Standard Deviation 0.816 |
| Feladilimab + Ipilimumab | Part 1: Change From Baseline in Potential of Hydrogen (pH) of Urine | WEEK 29 (Treatment Discontinuation) | -0.50 Potential of Hydrogen (pH) | Standard Deviation 0.866 |
| Feladilimab + Ipilimumab | Part 1: Change From Baseline in Potential of Hydrogen (pH) of Urine | WEEK 4 | -0.80 Potential of Hydrogen (pH) | Standard Deviation 0.975 |
| Feladilimab + Ipilimumab | Part 1: Change From Baseline in Potential of Hydrogen (pH) of Urine | WEEK 7 | -0.50 Potential of Hydrogen (pH) | Standard Deviation 0.707 |
| Feladilimab + Ipilimumab | Part 1: Change From Baseline in Potential of Hydrogen (pH) of Urine | WEEK 10 | 0.00 Potential of Hydrogen (pH) | — |
| Feladilimab + Ipilimumab | Part 1: Change From Baseline in Potential of Hydrogen (pH) of Urine | WEEK 13 | 0.50 Potential of Hydrogen (pH) | — |
Primary
Part 1: Change From Baseline in Specific Gravity of Urine
Urine samples were collected from participants to analyze urine specific gravity. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Changes from baseline in specific gravity of urine were reported.
Time frame: Baseline (Day 1), week 4, week 7, week 10, week 13 and week 29 (Treatment Discontinuation)
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Feladilimab + Ipilimumab | Part 1: Change From Baseline in Specific Gravity of Urine | Baseline (Day 1) | 1.0175 Kilogram per cubic meter | Standard Deviation 0.00418 |
| Feladilimab + Ipilimumab | Part 1: Change From Baseline in Specific Gravity of Urine | WEEK 4 | 0.0050 Kilogram per cubic meter | Standard Deviation 0.01173 |
| Feladilimab + Ipilimumab | Part 1: Change From Baseline in Specific Gravity of Urine | WEEK 7 | 0.0150 Kilogram per cubic meter | Standard Deviation 0.01414 |
| Feladilimab + Ipilimumab | Part 1: Change From Baseline in Specific Gravity of Urine | WEEK 10 | 0.0000 Kilogram per cubic meter | — |
| Feladilimab + Ipilimumab | Part 1: Change From Baseline in Specific Gravity of Urine | WEEK 13 | 0.0250 Kilogram per cubic meter | — |
| Feladilimab + Ipilimumab | Part 1: Change From Baseline in Specific Gravity of Urine | WEEK 29 (Treatment Discontinuation) | 0.0017 Kilogram per cubic meter | Standard Deviation 0.00764 |
Primary
Part 1: Number of Participants With AE Leading to Dose Modifications
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. The number of participants who experienced AE leading to dose modifications were evaluated.
Time frame: Up to 29 weeks
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Feladilimab + Ipilimumab | Part 1: Number of Participants With AE Leading to Dose Modifications | 1 Participants |
Primary
Part 1: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involved medical or scientific judgment or is associated with liver injury and impaired liver function. SAEs are subset of AEs. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA dictionary).
Time frame: Up to 29 weeks
Population: Safety Population included all participants who received at least one dose of treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 8 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 3 Participants |
Primary
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
Criteria for dose-limiting toxicity (DLT) included hematologic indicators such as febrile neutropenia as defined by CTCAE v5; Grade 4 neutropenia of \>7 days in duration; Grade 4 anemia and Grade 3-4 thrombocytopenia with bleeding. Non-hematologic criteria, comprising Grade 4 toxicity; Grade 3 pneumonitis of any duration; Grade 3 toxicity that does not resolve to ≤Grade 1 or baseline within 3 days despite optimal supportive care; any Grade 2 ocular toxicity requiring systemic steroids, or any ≥ Grade 3 ocular toxicity Any other toxicity considered to be dose-limiting that occurs beyond four weeks was considered as DLT. Any other event which in the judgment of the investigator and GSK Medical Monitor is considered to be a DLT.
Time frame: Up to 21 days
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 2 Participants |
Primary
Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters
Blood samples were collected for evaluation of clinical chemistry parameters. The summaries of worst-case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The number of participants with decreases to low from baseline, changes to normal or no changes from baseline, and increases to high values have been presented. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date.
Time frame: Baseline (Day 1) and up to 29 weeks
Population: Safety Population. Only those participants with data available in specified categories have been analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Albumin, Decrease to Low | 2 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Calcium, Decrease to Low | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Calcium, Change to Normal or No Change | 7 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Calcium, Increase to High | 1 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Creatinine, Change to Normal or No Change | 6 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Creatinine, Increase to High | 1 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Glucose, Decrease to Low | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Glucose, Change to Normal or No Change | 7 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Protein, Increase to High | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Sodium, Decrease to Low | 1 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Thyrotropin, Change to Normal or No Change | 5 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Thyrotropin, Increase to High | 2 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Triiodothyronine, Free, Increase to High | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Troponin T, Decrease to Low | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Urea, Change to Normal or No Change | 3 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Alanine aminotransferase (ALT), Decrease to Low | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | ALT, Change to Normal or No Change | 6 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | ALT, Increase to High | 2 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Albumin, Change to Normal or No Change | 6 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Albumin, Increase to High | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Alkaline Phosphatase (AP), Decrease to Low | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | AP, Change to Normal or No Change | 8 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | AP, Increase to High | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Aspartate Aminotransferase (AST), Decrease to Low | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | AST, Change to Normal or No Change | 8 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | AST, Increase to High | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Bilirubin, Decrease to Low | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Bilirubin, Change to Normal or No Change | 8 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Bilirubin, Increase to High | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | C Reactive Protein (mg/L), Decrease to Low | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | C Reactive Protein, Change to Normal or No Change | 3 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | C Reactive Protein, Increase to High | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Creatinine, Decrease to Low | 1 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Glucose, Increase to High | 1 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Lactate Dehydrogenase (LDH), Decrease to Low | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | LDH, Change to Normal or No Change | 8 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | LDH, Increase to High | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Potassium, Decrease to Low | 1 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Potassium, Change to Normal or No Change | 7 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Potassium, Increase to High | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Protein, Decrease to Low | 1 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Protein, Change to Normal or No Change | 7 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Sodium, Change to Normal or No Change | 7 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Sodium, Increase to High | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Thyrotropin, Decrease to Low | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Triiodothyronine, Free, Decrease to Low | 1 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Triiodothyronine, Free, Change to Normal or No Change | 3 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Troponin T, Change to Normal or No Change | 2 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Troponin T, Increase to High | 1 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Urea, Decrease to Low | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters | Urea, Increase to High | 5 Participants |
Primary
Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters
Blood samples were collected for evaluation of hematology parameters. The summaries of worst-case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by CTCAE v5.0. The number of participants with decreases to low from baseline, changes to normal or no changes from baseline, and increases to high values have been presented. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date.
Time frame: Baseline (Day 1) and up to 29 weeks
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Basophils, Change to Normal or No Change | 8 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Eosinophils, Decrease to Low | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Eosinophils, Increase to High | 1 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Erythrocytes, Decrease to Low | 2 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Ery. Mean Corpuscular HGB Concentration (EMCHC), Decrease to Low | 1 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Ery. Mean Corpuscular Volume (EMCV), Decrease to Low | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | EMCV, Change to Normal or No Change | 7 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | EMCV, Increase to High | 1 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Hematocrit, Decrease to Low | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Lymphocytes, Increase to High | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Basophils, Decrease to Low | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Basophils, Increase to High | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Eosinophils, Change to Normal or No Change | 7 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Erythrocytes, Change to Normal or No Change | 6 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Erythrocytes, Increase to High | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Hemoglobin, Decrease to Low | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Hemoglobin, Change to Normal or No Change | 8 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Hemoglobin, Increase to High | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | EMCHC, Change to Normal or No Change | 7 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | EMCHC, Increase to High | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Ery. Mean Corpuscular Hemoglobin (EMCH), Decrease to Low | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | EMCH, Change to Normal or No Change | 7 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | EMCH, Increase to High | 1 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Hematocrit, Change to Normal or No Change | 8 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Hematocrit, Increase to High | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Leukocytes, Decrease to Low | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Leukocytes, Change to Normal or No Change | 7 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Leukocytes, Increase to High | 1 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Lymphocytes, Decrease to Low | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Lymphocytes, Change to Normal or No Change | 8 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Monocytes, Decrease to Low | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Monocytes, Change to Normal or No Change | 7 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Monocytes, Increase to High | 1 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Neutrophils, Decrease to Low | 0 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Neutrophils, Change to Normal or No Change | 6 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Neutrophils, Increase to High | 2 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Platelets, Decrease to Low | 1 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Platelets, Change to Normal or No Change | 6 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters | Platelets, Increase to High | 1 Participants |
Primary
Part 1: Number of Participants With Worst Case Change Post-baseline in Urinalysis Parameters
Urine samples were collected for evaluation of urinalysis parameters using dipstick method. The dipstick test gave results in a semi-quantitative manner. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. The summaries of worst-case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by CTCAE v5.0. The number of participants with 'Any increase', or 'no changes/decreased' values have been presented.
Time frame: Baseline (Day 1) and up to 29 weeks
Population: Safety Population. Only those participants with data available in specified categories have been analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst Case Change Post-baseline in Urinalysis Parameters | Occult Blood, No Change/Decreased | 6 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst Case Change Post-baseline in Urinalysis Parameters | Protein, Any Increase | 3 Participants |
| Feladilimab + Ipilimumab | Part 1: Number of Participants With Worst Case Change Post-baseline in Urinalysis Parameters | Protein, No Change/Decreased | 3 Participants |
Primary
Part 2: Overall Survival
OS is defined as the time from randomization until death due to any cause.
Time frame: Up to 29 weeks
Population: No participants were enrolled in Part 2 as study was terminated.
Secondary
Part 1: Disease Control Rate (DCR)
DCR was defined as the percentage of participants with a confirmed CR + PR at any time, plus stable disease (SD) \>=12 weeks. PR was defined as at least 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 mm. Stable Disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.
Time frame: Up to 29 weeks
Population: Safety population. No participants had CR, PR, and SD.
Secondary
Part 1: Maximum Concentration (Cmax) and Minimum Concentration (Cmin)
Blood samples were collected for PK analysis.
Time frame: Up to 29 weeks
Population: PK Population included all participants from the ITT Population from whom a blood sample is obtained and analyzed for PK concentration. As a result of the study termination, none of the participants had sufficient samples for analysis. Consequently, data was neither collected nor analyzed, and data will never be analyzed for this outcome measure in the future.
Secondary
Part 1: Overall Response Rate (ORR)
ORR was defined as the percentage of participants who had a confirmed complete response (CR) or confirmed partial response (PR) as their best overall response (BOR) recorded from the date of randomization until disease progression or initiation of new anti-cancer therapy, whichever is earlier based on blinded independent central review (BICR) evaluation criteria in solid tumors (RECIST) version 1.1 (v1.1). CR was defined as disappearance of all target lesions. Any pathological lymph nodes must be \<10 millimeter in the short axis. PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters (e.g., percent change from baseline).
Time frame: Up to 29 weeks
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Feladilimab + Ipilimumab | Part 1: Overall Response Rate (ORR) | Complete response | 0 Percentage of participants |
| Feladilimab + Ipilimumab | Part 1: Overall Response Rate (ORR) | Partial response | 0 Percentage of participants |
Secondary
Part 2: Maximum Concentration (Cmax) and Minimum Concentration (Cmin)
Blood samples were planned to be collected for PK analysis.
Time frame: Up to 29 weeks
Population: No participants were enrolled in Part 2 as study was terminated.
Secondary
Part 2: Milestone Survival Rate at 12 and 18 Months
Milestone survival rate is the proportion of participants who are alive at a specific, predefined point in time after a certain event or diagnosis post treatment.
Time frame: At 12 and 18 months
Population: No participants were enrolled in Part 2 as study was terminated.
Secondary
Part 2: Number of Participants With AEs and SAEs
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function. AEs and SAEs were planned to be coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding system.
Time frame: Up to 29 weeks
Population: No participants were enrolled in Part 2 as study was terminated.
Secondary
Part 2: Number of Participants With AEs and SAEs Leading to Dose Modification
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function. AEs and SAEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding system. Number of participants with AEs and SAEs leading to dose modification (delays/withdrawal) were planned to be evaluated.
Time frame: Up to 29 weeks
Population: No participants were enrolled in Part 2 as study was terminated.
Secondary
Part 2: Number of Participants With AESI
Number of participants with AESI were planned to be evaluated.
Time frame: Up to 29 weeks
Population: No participants were enrolled in Part 2 as study was terminated.
Secondary
Part 2: Number of Participants With Clinically Significant Changes in Clinical Chemistry Lab Parameters
Blood samples were to be collected for the analysis of chemistry parameters. The laboratory parameters were to be graded according to CTCAE version 5. G1: mild; G2: moderate; G3: severe or medically significant. Higher grade indicates greater severity and an increase in CTCAE grade were to be defined relative to the Baseline grade.
Time frame: Up to 29 weeks
Population: No participants were enrolled in Part 2 as study was terminated.
Secondary
Part 2: Number of Participants With Clinically Significant Changes in Hematology Lab Parameters
Blood samples were to be collected for the analysis of hematology parameters. The laboratory parameters were to be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5. Grade 1 (G1): mild; Grade 2 (G2): moderate; Grade 3 (G3): severe or medically significant. Higher grade indicates greater severity and an increase in CTCAE grade were to be defined relative to the Baseline grade.
Time frame: Up to 29 weeks
Population: No participants were enrolled in Part 2 as study was terminated.
Secondary
Part 2: Number of Participants With Clinically Significant Changes in Vital Signs
Vital signs were planned to be measured after 5 minutes of rest and taken in the same position throughout the study.
Time frame: Up to 29 weeks
Population: No participants were enrolled in Part 2 as study was terminated.
Secondary
Part 2: Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD) Based on RECIST 1.1
Complete Response \[CR\], Partial Response \[PR\], stable disease \[SD\], and progressive disease (PD) as assessed by the investigator per IMWG. CR defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 mm; PR was defined as at least 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters; Stable Disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started.
Time frame: Up to 29 weeks
Population: No participants were enrolled in Part 2 as study was terminated.
Secondary
Part 2: Number of Participants With iPFS, iORR, and iDOR
iPFS defined as time from the date of randomization to the date of disease progression or death, whichever will occurs earlier, per iRECIST criteria. iORR defined as the percentage of participants with a confirmed iCR or iPR at any time per iRECIST criteria. iDOR defined as the time from first documented evidence of CR or PR until disease progression or death, per iRECIST criteria.
Time frame: Up to 29 weeks
Population: No participants were enrolled in Part 2 as study was terminated.
Secondary
Part 2: Number of Participants With iRECIST Complete Response (iCR), iRECIST Partial Response (iPR), iRECIST Stable Disease (iSD), iRECIST Confirmed Progressive Disease (iCPD), and iRECIST Unconfirmed Progressive Disease (iUPD)
Modified RECIST 1.1 for immune-based therapeutics (iRECIST) is based on RECIST v 1.1 but adapted to account for the unique tumor response seen with immunotherapeutic drugs. iRECIST was to be used to assess tumor response and progression and make treatment decisions. iCR: disappearance of all target lesions; iPR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g. percent change from baseline). iCPD: either 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; iSD: stable disease in the absence of CR or PD and iUPD: unconfirmed progressive disease when PD is unconfirmed.
Time frame: Up to 29 weeks
Population: No participants were enrolled in Part 2 as study was terminated.
Secondary
Part 2: Number of Participants With PFS, ORR, DOR, and DCR
PFS defined as time from the date of randomization to the date of disease progression or death, whichever will occurs earlier, per RECIST criteria. ORR defined as the percentage of participants with a confirmed CR or PR at any time per RECIST criteria. DOR defined as the time from first documented evidence of CR or PR until disease progression or death, per RECIST criteria. DCR was defined as the percentage of participants with a confirmed CR + PR at any time, plus stable disease (SD) \>=12 weeks.
Time frame: Up to 29 weeks
Population: No participants were enrolled in Part 2 as study was terminated.
Secondary
Part 2: Number of Participants With Post-baseline Positive Anti-drug Antibodies (ADAs) Against Feladilimab
Serum samples were to be collected for the analysis of the presence of ADAs using validated immunoassays.
Time frame: Up to 29 weeks
Population: No participants were enrolled in Part 2 as study was terminated.
Secondary
Part 2: Number of Participants With Post-baseline Positive Anti-drug Antibodies (ADAs) Against Iplimumab
Serum samples were to be collected for the analysis of the presence of ADAs using validated immunoassays.
Time frame: Up to 29 weeks
Population: No participants were enrolled in Part 2 as study was terminated.