Malignant Melanoma
Conditions
Keywords
Melanoma, Phase I, Biologic
Brief summary
IMCgp100 is a new biological therapy designed for the treatment of melanoma skin cancer. The drug is designed to target melanoma cells and stimulate immune cells to kill them. This trial is designed to establish the level of drug that can be given to a patient that is tolerable. It also designed to establish the best dosing schedule for the drug and to look for signals that the drug is working as intended.
Detailed description
IMCgp100 is a bispecific biologic incorporating an engineered T cell receptor (TCR) specific for a peptide antigen derived from the protein gp100 presented in the context of HLA A2 on the surface of melanoma cells. The TCR is fused to an anti-CD3 antibody single-chain variable fragment (scFv) that recruits and activates non-melanoma specific T cells (killer T cells) in physical contact with the cancer T cell. This is a Phase I study designed to assess the safety profile and establish a tolerable dose of IMCgp100 in HLA A2 positive malignant melanoma patients. The study has two treatment arms with different treatment schedules, weekly or daily dosing. Each treatment arm in the study has two parts. In the first part, dose escalation, the safety and tolerability of the drug are examined and the optimal dose of drug is established. In the second part of the trial, participants will receive an extended course of treatment with a view to assessing the effect of the drug on disease.
Interventions
DRUGIMCgp100
For each arm, the study will be divided into two parts: In part 1, dose escalation, the MTD or RP2D for each dosing regimen will be established. In part 2, dose expansion, a cohort of participants will be treated at the RP2D or MTD.
Sponsors
Immunocore Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Pathologically documented Stage IV malignant melanoma or unresectable Stage III melanoma for which no standard effective therapy exists or for which an appropriate window exists between alternative therapeutic options. Participants for whom early treatment with vemurafenib is indicated, e.g. rapidly progressing or symptomatic disease, are excluded from this trial. 2. Previous surgery (other than resection of skin metastases), radiotherapy, chemotherapy, immunotherapy or experimental therapy completed \> 4 weeks before and all adverse events resolved to ≤ grade 1. In cases where localized radiotherapy has been applied, treatment with IMCgp100 can be commenced after a two week period. 3. Human leukocyte antigen (HLA) A2 positive. 4. ≥ 18 years old. 5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1. 6. Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. Participants participating in the dose escalation part of Arm 2 only require assessable disease. 7. Life expectancy \> 3 months. 8. Blood tests within the following parameters: 1. Platelet count ≥ 100 x10⁹/L 2. Hemoglobin ≥ 9g/dL (blood transfusion to achieve this level is permitted) 3. Calculated creatinine clearance ≥ 50 mL/min using the modified Cockroft-Gault equation 4. Neutrophil count ≥1x10⁹/L 5. Lymphocyte count ≥ 0.5x10⁹/L 9. Female participants of childbearing potential must use maximally effective birth control during the period of therapy, must be willing to use contraception for 6 months following the last study drug infusion and must have a negative urine or serum pregnancy test upon entry into this study. Otherwise, female participants must be postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile. 10. Male participants must be surgically sterile or willing to use a double barrier contraception method upon enrollment, during the course of the study, and for 6 months following the last study drug infusion. 11. Participants with a history of adrenal insufficiency, maintained on stable replacement dose corticosteroid (\< 10 mg/d prednisone or the equivalent) are eligible for treatment with IMCgp100, unless there is a past history of adrenal crisis. Eligible participants with a history of adrenal insufficiency receiving replacement dose corticosteroid must receive prophylactic stress dose corticosteroid prior to dosing during the first four doses of IMCgp100 treatment, regardless of weekly or daily dosing regimen. 12. Able to give informed consent.
Exclusion criteria
Participants meeting any of the following criteria will be excluded from the study: 1. Symptomatic brain metastases that are unstable, require steroids, or that have required radiation within the last 28 days. 2. Other active malignancy in the past 5 years except carcinoma in situ, completely excised nonmelanomatous skin cancer or any other malignancy that in the opinion of the investigator is considered to be cured. 3. Comorbid medical condition that would increase the risk of toxicity in the opinion of the investigator or sponsor. Symptomatic on-going infection must be resolved before the patient can be treated in the study. 4. Uveitis. 5. Had myocardial infarction within 1 year before enrolment, symptomatic congestive heart failure (New York Heart Association \> Class II), unstable angina or unstable cardiac arrhythmia requiring medication. 6. Has an ejection fraction \< 50%. 7. Clinically significant electrocardiogram (ECG) changes that obscure the ability to assess the RR, PR and QT intervals. Participants with corrected QT interval (QTc) calculated by Bazetts or locally preferred formula which is greater than 500 ms. 8. Has hepatic function as follows: 1. Aspartate aminotransferase \> 2.5 x upper limit of normal (ULN) 2. Alanine aminotransferase \> 2.5 x ULN 3. Bilirubin \> 2.0 x ULN 4. Prothrombin time or partial thromboplastin time \> 1.5 x ULN 9. Bleeding diathesis 10. Immunosuppressive condition or treatment including previous transplantation, splenectomy or known human immunodeficiency virus (HIV) infection. 11. Has a history of adult seizures. 12. Participants with evidence of a raised intracranial pressure in Arm 2 of the study who will have a cerebrospinal fluid sample taken. 13. Participants receiving chronic corticosteroid treatment (longer than 8 weeks duration) for management of pre-existing adverse events at any dose, or participants with a history of chronic corticosteroid treatment longer than 8 weeks duration for adverse events within 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of IMCgp100 Administered Weekly (Dose Escalation Part) | Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8 | The maximum tolerated dose (MTD) for IMCgp100 administered by weekly dosing was determined based on the frequency of dose-limiting toxicity (DLT) occurring during Days 1 to 8. Participants presented at MTD in the dose escalation phase. Abbreviations: ng/kg=nanograms/kilogram |
| MTD of IMCgp100 Administered Daily (Dose Escalation Part) | Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8 | The MTD for IMCgp100 administered by daily dosing was determined based on the frequency of DLT occurring during Days 1 to 8. The 50 mcg dose was the RP2D for daily dosing, as the MTD was not achieved. Abbreviations: mcg=micrograms |
| Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Day 1 (first dose), 30 days after the last dose | Treatment-emergent adverse events (TEAEs) were defined as adverse events (AEs) with an onset date after the date of first dose and within 30 days after the last administration of study medication in either treatment arm. AEs with missing date of onset were considered treatment emergent. |
| Number of Participants Experiencing Clinically Significant Laboratory Parameters (Hematology) | 28 months | Laboratory parameters included clinical chemistry, hematology, and urinalysis. For hematology, this included red cell count, hemoglobin, hematocrit, mean cell volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, leukocyte differential count (percentage or absolute), prothrombin time, and activated partial tissue thromboplastin time. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose. |
| Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Hematology) | 28 months | Laboratory parameters included clinical chemistry, hematology, and urinalysis. For hematology, this included red cell count, hemoglobin, hematocrit, mean cell volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, leukocyte differential count (percentage or absolute), prothrombin time, and activated partial tissue thromboplastin time. Laboratory parameter abnormalities were graded by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 at any time on treatment from normal pre-dose. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death. |
| Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry) | 28 months | Laboratory parameters included clinical chemistry, hematology, and urinalysis. Clinical chemistry parameters included calcium, phosphorus, magnesium, albumin, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, lactate dehydrogenase, sodium, potassium, bicarbonate, creatinine, chloride, glucose, urea, uric acid, and C-reactive protein. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose. |
| Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Clinical Chemistry) | 28 months | Laboratory parameters included clinical chemistry, hematology, and urinalysis. Clinical chemistry parameters included calcium, phosphorus, magnesium, albumin, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, lactate dehydrogenase, sodium, potassium, bicarbonate, creatinine, chloride, glucose, urea, uric acid, and C-reactive protein. Laboratory parameter abnormalities were graded by the investigator using CTCAE v 4.0 at any time on treatment from normal pre-dose. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death. |
| Number of Participants Experiencing Clinically Significant Electrocardiograms (ECGs) | 28 months | Twelve lead ECGs were obtained after the participant has rested in a supine position for at least 5 minutes. Clinically significant findings were defined as such in the opinion of the investigator or designated physician occurring at any time on treatment from normal pre-dose. |
| Number of Participants Experiencing Clinically Significant Vital Signs | 28 months | Vital signs included temperature, blood pressure, respiration rate, and heart rate. Measurements were made after the participant had been resting supine for a minimum of 5 minutes. Blood pressure and heart rate were measured using a recording device with an appropriate cuff size. Temperature and respiration rate were measured as per clinical practice. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose. |
| Number of Participants Experiencing Clinically Significant Physical Examination Results (Weight Decrease) | 28 months | Physical examination included weight, a record of skin pigmentation, and photographic record of any vitiligo if present. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose. |
| Number of Participants Experiencing ≥Grade 3 Severity in Physical Examination Results (Skin Pigmentation) | 28 months | Physical examination included weight, a record of skin pigmentation, and photographic record of any vitiligo if present. Abnormalities were graded by the investigator using CTCAE v 4.0 at any time on treatment from normal pre-dose. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC of IMCgp100 of 900 ng/kg By-weight Dose (Dose Escalation and Dose Expansion Parts) | Day 1, Cycle 1 | The AUC, measured in h\*pg/ml, is a method of measurement of the total exposure of a drug in blood. |
| Number of Participants With Best Overall Response Per Response Evaluation Criteria In Solid Tumors (RECIST) (Weekly Dosing-Dose Expansion Part) | 28 months | The best overall response was assigned as complete response (CR), partial response (PR), minor response, stable disease, progressive disease (PD) or not evaluable (NE) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. |
| AUC of IMCgp100 of 50 mcg Flat Dose (Dose Escalation and Dose Expansion Parts) | Day 1, Cycle 1 | The AUC (measured in h\*pg/ml) is a method of measurement of the total exposure of a drug in blood. |
| AUC of IMCgp100 Flat Dose (Dose Escalation and Dose Expansion Parts) | Day 1, Cycle 1 | The AUC (measured in h\*pg/ml) is a method of measurement of the total exposure of a drug in blood. Participants in the 20 mcg and 40 mcg dose groups received intra-participant dose-escalation up to 50 mcg on Day 15. |
| Number of Participants With Anti-IMCgp100 Antibody Formation (Dose Escalation and Dose Expansion Parts) | 28 months | To provide a comprehensive anti-drug antibody (ADA) summary for the study, individual participant data were combined and assessed as distinct groups based on characteristics of their ADA response. Evaluable participants were those with post-drug administration samples. ADA prevalence (pre- existing antibody response) was measured as the number of baseline-positive participant out of all participants who provided baseline samples. Overall ADA incidence was calculated based on the combined number of treatment-boosted and treatment-induced ADA-positive participants. The treatment-induced incidence was determined as the number of ADA- positive participants of those that were ADA-negative at baseline; while treatment-boosted incidence was determined as the number of participants with an ADA titer increase equal to or greater than the minimum significant dilution (3-fold) of the assay. |
| Estimated Maximum Plasma Concentration (Cmax) of IMCgp100 By-weight Doses (Dose Escalation) | Day 1, Cycle 1 | The maximum plasma concentration (Cmax) is the highest concentration that a drug achieves in the blood after administration in a dosing interval. Abbreviations: ng/kg = nanograms/kilogram |
| Estimated Cmax of IMCgp100 of 900 ng/kg By-weight Dose (Dose Escalation and Dose Expansion Parts) | Day 1, Cycle 1 | The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. |
| Estimated Cmax of IMCgp100 Flat Dose (Dose Escalation and Dose Expansion Parts) | Day 1, Cycle 1 | The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. Abbreviations: mcg = micrograms |
| Estimated Cmax of IMCgp100 of 600 ng/kg By-weight Dose (Dose Escalation) | Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50 | The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. |
| Estimated Cmax of IMCgp100 of 20/30/50 mcg Flat Dose (Dose Escalation) | Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50 | The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. On Day 1, IMCgp100 20 mcg was given, IMCgp100 30 mcg was administered on Day 8, and IMCgp100 50 mcg was dosed on Days 15 and after. |
| Estimated Cmax of IMCgp100 of 40/40/50 mcg Flat Dose (Dose Escalation) | Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50 | The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. This dosing regimen was implemented following the Urgent Safety Measure to adapt the dosing in the Phase 1 study that dropped Dose 1 to 40 mcg from the identified 50 mcg RP2D. |
| Estimated Cmax of IMCgp100 of 50 mcg Flat Dose (Dose Escalation) | Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50 | The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. The RP2D identified in this study following review of all safety and pharmacokinetic data in the dose escalation of the Phase 1 study was the 50 mcg flat dose. |
| Estimated Cmax of IMCgp100 of a Single Infusion Flat Dose (Dose Escalation) | Cycle 1: Day 1 | The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. |
| Area Under the Concentration-Time Curve (AUC) of IMCgp100 By-weight Dose (Dose Escalation) | Day 1, Cycle 1 | The area under the concentration-time curve (AUC), measured in hours by picograms per milliliter ( h\*pg/ml) is a method of measurement of the total exposure of a drug in blood. |
Countries
United Kingdom, United States
Participant flow
Pre-assignment details
All-patients population and safety population both comprised 84 participants who enrolled in the study and who also received at least one IMCgp100 dose; the all-patients and safety population for Arm 1 was 66 participants and for Arm 2 was 18 participants. Efficacy population was 54 participants in Arm 1 and 15 participants in Arm 2.
Participants by arm
| Arm | Count |
|---|---|
| IMCgp100 Weekly Dosing Regimen Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each. | 66 |
| IMCgp100 Daily Dosing Regimen Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle | 18 |
| Total | 84 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 0 |
| Overall Study | Other | 0 | 1 |
| Overall Study | Progressive Disease | 18 | 9 |
| Overall Study | Withdrawal of Consent | 1 | 0 |
Baseline characteristics
| Characteristic | IMCgp100 Daily Dosing Regimen | Total | IMCgp100 Weekly Dosing Regimen |
|---|---|---|---|
| Age, Continuous | 60.4 years | 58.7 years | 58.2 years |
| Race/Ethnicity, Customized Asian | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Black | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Other | 1 participants | 3 participants | 2 participants |
| Race/Ethnicity, Customized White | 17 participants | 79 participants | 62 participants |
| Sex: Female, Male Female | 5 Participants | 30 Participants | 25 Participants |
| Sex: Female, Male Male | 13 Participants | 54 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 8 / 66 | 8 / 18 |
| other Total, other adverse events | 66 / 66 | 18 / 18 |
| serious Total, serious adverse events | 24 / 66 | 5 / 18 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of IMCgp100 Administered Weekly (Dose Escalation Part)
The maximum tolerated dose (MTD) for IMCgp100 administered by weekly dosing was determined based on the frequency of dose-limiting toxicity (DLT) occurring during Days 1 to 8. Participants presented at MTD in the dose escalation phase. Abbreviations: ng/kg=nanograms/kilogram
Time frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Population: Safety population: all participants who received at least 1 dose of IMCgp100, up to a maximum of 600 ng/kg.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMCgp100 Weekly Dosing Regimen | Maximum Tolerated Dose (MTD) of IMCgp100 Administered Weekly (Dose Escalation Part) | 600 ng/kg |
Primary
MTD of IMCgp100 Administered Daily (Dose Escalation Part)
The MTD for IMCgp100 administered by daily dosing was determined based on the frequency of DLT occurring during Days 1 to 8. The 50 mcg dose was the RP2D for daily dosing, as the MTD was not achieved. Abbreviations: mcg=micrograms
Time frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Population: Safety population: all participants who received at least 1 dose of IMCgp100
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMCgp100 Weekly Dosing Regimen | MTD of IMCgp100 Administered Daily (Dose Escalation Part) | 50 mcg |
Primary
Number of Participants Experiencing Clinically Significant Electrocardiograms (ECGs)
Twelve lead ECGs were obtained after the participant has rested in a supine position for at least 5 minutes. Clinically significant findings were defined as such in the opinion of the investigator or designated physician occurring at any time on treatment from normal pre-dose.
Time frame: 28 months
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Electrocardiograms (ECGs) | 3 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Electrocardiograms (ECGs) | 0 number of participants |
Primary
Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry)
Laboratory parameters included clinical chemistry, hematology, and urinalysis. Clinical chemistry parameters included calcium, phosphorus, magnesium, albumin, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, lactate dehydrogenase, sodium, potassium, bicarbonate, creatinine, chloride, glucose, urea, uric acid, and C-reactive protein. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose.
Time frame: 28 months
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry) | Aspartate Aminotransferase | 1 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry) | Calcium | 0 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry) | Alkaline Phosphatase | 3 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry) | Glucose | 1 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry) | Magnesium | 0 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry) | Alanine Aminotransferase | 1 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry) | Sodium | 0 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry) | Albumin | 3 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry) | Uric Acid | 1 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry) | Potassium | 1 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry) | Uric Acid | 0 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry) | Albumin | 3 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry) | Alkaline Phosphatase | 1 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry) | Aspartate Aminotransferase | 2 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry) | Alanine Aminotransferase | 1 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry) | Potassium | 1 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry) | Calcium | 1 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry) | Magnesium | 1 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry) | Sodium | 1 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry) | Glucose | 0 number of participants |
Primary
Number of Participants Experiencing Clinically Significant Laboratory Parameters (Hematology)
Laboratory parameters included clinical chemistry, hematology, and urinalysis. For hematology, this included red cell count, hemoglobin, hematocrit, mean cell volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, leukocyte differential count (percentage or absolute), prothrombin time, and activated partial tissue thromboplastin time. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose.
Time frame: 28 months
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Hematology) | Lymphocytes | 12 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Hematology) | CD4 Cells | 1 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Hematology) | Neutrophils | 1 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Hematology) | Leukocytes | 1 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Hematology) | Hemoglobin | 1 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Hematology) | Leukocytes | 0 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Hematology) | Lymphocytes | 1 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Hematology) | Hemoglobin | 2 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Hematology) | Neutrophils | 0 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Laboratory Parameters (Hematology) | CD4 Cells | 0 number of participants |
Primary
Number of Participants Experiencing Clinically Significant Physical Examination Results (Weight Decrease)
Physical examination included weight, a record of skin pigmentation, and photographic record of any vitiligo if present. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose.
Time frame: 28 months
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Physical Examination Results (Weight Decrease) | 3 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Physical Examination Results (Weight Decrease) | 1 number of participants |
Primary
Number of Participants Experiencing Clinically Significant Vital Signs
Vital signs included temperature, blood pressure, respiration rate, and heart rate. Measurements were made after the participant had been resting supine for a minimum of 5 minutes. Blood pressure and heart rate were measured using a recording device with an appropriate cuff size. Temperature and respiration rate were measured as per clinical practice. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose.
Time frame: 28 months
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Vital Signs | High Diastolic Blood Pressure | 20 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Vital Signs | High Heart Rate | 34 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Vital Signs | Low Systolic Blood Pressure | 8 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Vital Signs | Low Heart Rate | 8 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Vital Signs | Low Diastolic Blood Pressure | 37 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Vital Signs | High Temperature | 33 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing Clinically Significant Vital Signs | High Systolic Blood Pressure | 17 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Vital Signs | High Temperature | 13 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Vital Signs | High Systolic Blood Pressure | 2 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Vital Signs | Low Systolic Blood Pressure | 5 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Vital Signs | High Diastolic Blood Pressure | 3 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Vital Signs | Low Diastolic Blood Pressure | 12 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Vital Signs | High Heart Rate | 12 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing Clinically Significant Vital Signs | Low Heart Rate | 1 number of participants |
Primary
Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Clinical Chemistry)
Laboratory parameters included clinical chemistry, hematology, and urinalysis. Clinical chemistry parameters included calcium, phosphorus, magnesium, albumin, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, lactate dehydrogenase, sodium, potassium, bicarbonate, creatinine, chloride, glucose, urea, uric acid, and C-reactive protein. Laboratory parameter abnormalities were graded by the investigator using CTCAE v 4.0 at any time on treatment from normal pre-dose. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death.
Time frame: 28 months
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Clinical Chemistry) | Potassium-Grade 3 | 2 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Clinical Chemistry) | Aspartate Aminotransferase-Grade 3 | 1 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Clinical Chemistry) | Glucose-Grade 3 | 1 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Clinical Chemistry) | Calcium-Grade 3 | 0 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Clinical Chemistry) | Sodium-Grade 3 | 2 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Clinical Chemistry) | Calcium-Grade 3 | 1 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Clinical Chemistry) | Sodium-Grade 3 | 4 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Clinical Chemistry) | Potassium-Grade 3 | 1 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Clinical Chemistry) | Glucose-Grade 3 | 1 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Clinical Chemistry) | Aspartate Aminotransferase-Grade 3 | 0 number of participants |
Primary
Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Hematology)
Laboratory parameters included clinical chemistry, hematology, and urinalysis. For hematology, this included red cell count, hemoglobin, hematocrit, mean cell volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, leukocyte differential count (percentage or absolute), prothrombin time, and activated partial tissue thromboplastin time. Laboratory parameter abnormalities were graded by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 at any time on treatment from normal pre-dose. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death.
Time frame: 28 months
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Hematology) | Lymphocytes-Grade 3 | 15 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Hematology) | Lymphocytes-Grade 4 | 2 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Hematology) | CD4 Count-Grade 3 | 4 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Hematology) | CD4 Count-Grade 4 | 4 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Hematology) | Hemoglobin-Grade 3 | 0 number of participants |
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Hematology) | Leukocytes-Grade 3 | 1 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Hematology) | Hemoglobin-Grade 3 | 3 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Hematology) | Lymphocytes-Grade 3 | 2 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Hematology) | CD4 Count-Grade 4 | 1 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Hematology) | Lymphocytes-Grade 4 | 2 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Hematology) | Leukocytes-Grade 3 | 0 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Hematology) | CD4 Count-Grade 3 | 1 number of participants |
Primary
Number of Participants Experiencing ≥Grade 3 Severity in Physical Examination Results (Skin Pigmentation)
Physical examination included weight, a record of skin pigmentation, and photographic record of any vitiligo if present. Abnormalities were graded by the investigator using CTCAE v 4.0 at any time on treatment from normal pre-dose. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death.
Time frame: 28 months
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMCgp100 Weekly Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Physical Examination Results (Skin Pigmentation) | 0 number of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Experiencing ≥Grade 3 Severity in Physical Examination Results (Skin Pigmentation) | 0 number of participants |
Primary
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)
Treatment-emergent adverse events (TEAEs) were defined as adverse events (AEs) with an onset date after the date of first dose and within 30 days after the last administration of study medication in either treatment arm. AEs with missing date of onset were considered treatment emergent.
Time frame: Day 1 (first dose), 30 days after the last dose
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMCgp100 Weekly Dosing Regimen | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | 100.0 percentage of participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | 100.00 percentage of participants |
Secondary
Area Under the Concentration-Time Curve (AUC) of IMCgp100 By-weight Dose (Dose Escalation)
The area under the concentration-time curve (AUC), measured in hours by picograms per milliliter ( h\*pg/ml) is a method of measurement of the total exposure of a drug in blood.
Time frame: Day 1, Cycle 1
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| IMCgp100 Weekly Dosing Regimen | Area Under the Concentration-Time Curve (AUC) of IMCgp100 By-weight Dose (Dose Escalation) | 15 ng/kg | 5666.63 hours * picograms/milliliter | Geometric Coefficient of Variation 434.62 |
| IMCgp100 Weekly Dosing Regimen | Area Under the Concentration-Time Curve (AUC) of IMCgp100 By-weight Dose (Dose Escalation) | 45 ng/kg | 2965.10 hours * picograms/milliliter | Geometric Coefficient of Variation 49.17 |
| IMCgp100 Weekly Dosing Regimen | Area Under the Concentration-Time Curve (AUC) of IMCgp100 By-weight Dose (Dose Escalation) | 135 ng/kg | 2904.91 hours * picograms/milliliter | Geometric Coefficient of Variation 96.95 |
| IMCgp100 Weekly Dosing Regimen | Area Under the Concentration-Time Curve (AUC) of IMCgp100 By-weight Dose (Dose Escalation) | 270 ng/kg | 10649.19 hours * picograms/milliliter | Geometric Coefficient of Variation 40.82 |
| IMCgp100 Weekly Dosing Regimen | Area Under the Concentration-Time Curve (AUC) of IMCgp100 By-weight Dose (Dose Escalation) | 405 ng/kg | 33332.31 hours * picograms/milliliter | Geometric Coefficient of Variation 43.57 |
| IMCgp100 Weekly Dosing Regimen | Area Under the Concentration-Time Curve (AUC) of IMCgp100 By-weight Dose (Dose Escalation) | 600 ng/kg | 63507.24 hours * picograms/milliliter | Geometric Coefficient of Variation 43.97 |
| IMCgp100 Weekly Dosing Regimen | Area Under the Concentration-Time Curve (AUC) of IMCgp100 By-weight Dose (Dose Escalation) | 900 ng/kg | 97724.58 hours * picograms/milliliter | Geometric Coefficient of Variation 29.49 |
Secondary
AUC of IMCgp100 Flat Dose (Dose Escalation and Dose Expansion Parts)
The AUC (measured in h\*pg/ml) is a method of measurement of the total exposure of a drug in blood. Participants in the 20 mcg and 40 mcg dose groups received intra-participant dose-escalation up to 50 mcg on Day 15.
Time frame: Day 1, Cycle 1
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| IMCgp100 Weekly Dosing Regimen | AUC of IMCgp100 Flat Dose (Dose Escalation and Dose Expansion Parts) | 20 mcg | 3239.82 hours * picograms/milliliter | Geometric Coefficient of Variation 20.97 |
| IMCgp100 Weekly Dosing Regimen | AUC of IMCgp100 Flat Dose (Dose Escalation and Dose Expansion Parts) | 40 mcg | 59333.15 hours * picograms/milliliter | Geometric Coefficient of Variation 21.44 |
Secondary
AUC of IMCgp100 of 50 mcg Flat Dose (Dose Escalation and Dose Expansion Parts)
The AUC (measured in h\*pg/ml) is a method of measurement of the total exposure of a drug in blood.
Time frame: Day 1, Cycle 1
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| IMCgp100 Weekly Dosing Regimen | AUC of IMCgp100 of 50 mcg Flat Dose (Dose Escalation and Dose Expansion Parts) | 73134.57 hours * picograms/milliliter | Geometric Coefficient of Variation 55.88 |
Secondary
AUC of IMCgp100 of 900 ng/kg By-weight Dose (Dose Escalation and Dose Expansion Parts)
The AUC, measured in h\*pg/ml, is a method of measurement of the total exposure of a drug in blood.
Time frame: Day 1, Cycle 1
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| IMCgp100 Weekly Dosing Regimen | AUC of IMCgp100 of 900 ng/kg By-weight Dose (Dose Escalation and Dose Expansion Parts) | 97724.58 hours * picograms/milliliter | Geometric Coefficient of Variation 29.49 |
Secondary
Estimated Cmax of IMCgp100 Flat Dose (Dose Escalation and Dose Expansion Parts)
The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. Abbreviations: mcg = micrograms
Time frame: Day 1, Cycle 1
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 Flat Dose (Dose Escalation and Dose Expansion Parts) | 20 mcg | 3239.82 picograms/milliliter | Geometric Coefficient of Variation 20.97 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 Flat Dose (Dose Escalation and Dose Expansion Parts) | 40 mcg | 8316.43 picograms/milliliter | Geometric Coefficient of Variation 45.1 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 Flat Dose (Dose Escalation and Dose Expansion Parts) | 50 mcg | 8740.99 picograms/milliliter | Geometric Coefficient of Variation 38.01 |
Secondary
Estimated Cmax of IMCgp100 of 20/30/50 mcg Flat Dose (Dose Escalation)
The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. On Day 1, IMCgp100 20 mcg was given, IMCgp100 30 mcg was administered on Day 8, and IMCgp100 50 mcg was dosed on Days 15 and after.
Time frame: Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50
Population: PK Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 20/30/50 mcg Flat Dose (Dose Escalation) | Day 1 | 3299 mcg | Standard Deviation 660 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 20/30/50 mcg Flat Dose (Dose Escalation) | Day 8 | 5056 mcg | Standard Deviation 1175 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 20/30/50 mcg Flat Dose (Dose Escalation) | Day 15 | 7981 mcg | Standard Deviation 2278 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 20/30/50 mcg Flat Dose (Dose Escalation) | Day 22 | 6682 mcg | Standard Deviation 1395 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 20/30/50 mcg Flat Dose (Dose Escalation) | Day 29 | 4710 mcg | Standard Deviation 3621 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 20/30/50 mcg Flat Dose (Dose Escalation) | Day 36 | 7100 mcg | Standard Deviation 1535 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 20/30/50 mcg Flat Dose (Dose Escalation) | Day 43 | 7240 mcg | Standard Deviation 1906 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 20/30/50 mcg Flat Dose (Dose Escalation) | Day 50 | 6658 mcg | Standard Deviation 1211 |
Secondary
Estimated Cmax of IMCgp100 of 40/40/50 mcg Flat Dose (Dose Escalation)
The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. This dosing regimen was implemented following the Urgent Safety Measure to adapt the dosing in the Phase 1 study that dropped Dose 1 to 40 mcg from the identified 50 mcg RP2D.
Time frame: Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50
Population: PK Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 40/40/50 mcg Flat Dose (Dose Escalation) | Day 1 | 8847 mcg | Standard Deviation 3811 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 40/40/50 mcg Flat Dose (Dose Escalation) | Day 8 | 5340 mcg | Standard Deviation 311 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 40/40/50 mcg Flat Dose (Dose Escalation) | Day 15 | 8373 mcg | Standard Deviation 2682 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 40/40/50 mcg Flat Dose (Dose Escalation) | Day 22 | 7445 mcg | Standard Deviation 983 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 40/40/50 mcg Flat Dose (Dose Escalation) | Day 29 | 3288 mcg | Standard Deviation 4614 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 40/40/50 mcg Flat Dose (Dose Escalation) | Day 36 | 8073 mcg | Standard Deviation 1337 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 40/40/50 mcg Flat Dose (Dose Escalation) | Day 43 | 6735 mcg | Standard Deviation 672 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 40/40/50 mcg Flat Dose (Dose Escalation) | Day 50 | 7130 mcg | Standard Deviation 4483 |
Secondary
Estimated Cmax of IMCgp100 of 50 mcg Flat Dose (Dose Escalation)
The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. The RP2D identified in this study following review of all safety and pharmacokinetic data in the dose escalation of the Phase 1 study was the 50 mcg flat dose.
Time frame: Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50
Population: PK Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 50 mcg Flat Dose (Dose Escalation) | Day 50 | 9018 mcg | Standard Deviation 5001 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 50 mcg Flat Dose (Dose Escalation) | Day 1 | 9327 mcg | Standard Deviation 3802 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 50 mcg Flat Dose (Dose Escalation) | Day 8 | 6414 mcg | Standard Deviation 3653 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 50 mcg Flat Dose (Dose Escalation) | Day 15 | 7236 mcg | Standard Deviation 3304 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 50 mcg Flat Dose (Dose Escalation) | Day 22 | 7620 mcg | Standard Deviation 2710 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 50 mcg Flat Dose (Dose Escalation) | Day 29 | 8186 mcg | Standard Deviation 3178 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 50 mcg Flat Dose (Dose Escalation) | Day 36 | 8425 mcg | Standard Deviation 4594 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 50 mcg Flat Dose (Dose Escalation) | Day 43 | 6905 mcg | Standard Deviation 4097 |
Secondary
Estimated Cmax of IMCgp100 of 600 ng/kg By-weight Dose (Dose Escalation)
The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval.
Time frame: Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50
Population: PK Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 600 ng/kg By-weight Dose (Dose Escalation) | Day 1 | 7311 picograms/milliliter | Standard Deviation 1770 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 600 ng/kg By-weight Dose (Dose Escalation) | Day 8 | 5726 picograms/milliliter | Standard Deviation 3605 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 600 ng/kg By-weight Dose (Dose Escalation) | Day 15 | 6182 picograms/milliliter | Standard Deviation 1456 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 600 ng/kg By-weight Dose (Dose Escalation) | Day 22 | 6490 picograms/milliliter | Standard Deviation 2488 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 600 ng/kg By-weight Dose (Dose Escalation) | Day 29 | 6245 picograms/milliliter | Standard Deviation 3047 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 600 ng/kg By-weight Dose (Dose Escalation) | Day 36 | 6396 picograms/milliliter | Standard Deviation 3474 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 600 ng/kg By-weight Dose (Dose Escalation) | Day 43 | 6014 picograms/milliliter | Standard Deviation 1125 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 600 ng/kg By-weight Dose (Dose Escalation) | Day 50 | 7136 picograms/milliliter | Standard Deviation 2744 |
Secondary
Estimated Cmax of IMCgp100 of 900 ng/kg By-weight Dose (Dose Escalation and Dose Expansion Parts)
The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval.
Time frame: Day 1, Cycle 1
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of 900 ng/kg By-weight Dose (Dose Escalation and Dose Expansion Parts) | 8868.83 picograms/milliliter | Geometric Coefficient of Variation 27.92 |
Secondary
Estimated Cmax of IMCgp100 of a Single Infusion Flat Dose (Dose Escalation)
The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval.
Time frame: Cycle 1: Day 1
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of a Single Infusion Flat Dose (Dose Escalation) | 10 mcg | 997.83 picograms/milliliter | Geometric Coefficient of Variation 38.01 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of a Single Infusion Flat Dose (Dose Escalation) | 20 mcg | 3599.18 picograms/milliliter | Geometric Coefficient of Variation 15.42 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of a Single Infusion Flat Dose (Dose Escalation) | 30 mcg | 3599.18 picograms/milliliter | Geometric Coefficient of Variation 15.42 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of a Single Infusion Flat Dose (Dose Escalation) | 40 mcg | 6157.90 picograms/milliliter | Geometric Coefficient of Variation 29.52 |
| IMCgp100 Weekly Dosing Regimen | Estimated Cmax of IMCgp100 of a Single Infusion Flat Dose (Dose Escalation) | 50 mcg | 8111.79 picograms/milliliter | Geometric Coefficient of Variation 27.8 |
Secondary
Estimated Maximum Plasma Concentration (Cmax) of IMCgp100 By-weight Doses (Dose Escalation)
The maximum plasma concentration (Cmax) is the highest concentration that a drug achieves in the blood after administration in a dosing interval. Abbreviations: ng/kg = nanograms/kilogram
Time frame: Day 1, Cycle 1
Population: Pharmacokinetics (PK) Population: all participants who receive at least 1 dose of IMCgp100 and have at least 1 measurable PK concentration with the relevant date, time and dosing data for this sample.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| IMCgp100 Weekly Dosing Regimen | Estimated Maximum Plasma Concentration (Cmax) of IMCgp100 By-weight Doses (Dose Escalation) | 15 ng/kg by-weight dose | 305.50 picograms/milliliter | Geometric Coefficient of Variation 583.47 |
| IMCgp100 Weekly Dosing Regimen | Estimated Maximum Plasma Concentration (Cmax) of IMCgp100 By-weight Doses (Dose Escalation) | 45 ng/kg by-weight dose | 271.33 picograms/milliliter | Geometric Coefficient of Variation 21.49 |
| IMCgp100 Weekly Dosing Regimen | Estimated Maximum Plasma Concentration (Cmax) of IMCgp100 By-weight Doses (Dose Escalation) | 135 ng/kg by-weight dose | 371.79 picograms/milliliter | Geometric Coefficient of Variation 57.25 |
| IMCgp100 Weekly Dosing Regimen | Estimated Maximum Plasma Concentration (Cmax) of IMCgp100 By-weight Doses (Dose Escalation) | 270 ng/kg by-weight dose | 856.35 picograms/milliliter | Geometric Coefficient of Variation 41.01 |
| IMCgp100 Weekly Dosing Regimen | Estimated Maximum Plasma Concentration (Cmax) of IMCgp100 By-weight Doses (Dose Escalation) | 405 ng/kg by-weight dose | 2345.25 picograms/milliliter | Geometric Coefficient of Variation 35.74 |
| IMCgp100 Weekly Dosing Regimen | Estimated Maximum Plasma Concentration (Cmax) of IMCgp100 By-weight Doses (Dose Escalation) | 600 ng/kg by-weight dose | 6188.54 picograms/milliliter | Geometric Coefficient of Variation 41.21 |
| IMCgp100 Weekly Dosing Regimen | Estimated Maximum Plasma Concentration (Cmax) of IMCgp100 By-weight Doses (Dose Escalation) | 900 ng/kg by-weight dose | 8868.83 picograms/milliliter | Geometric Coefficient of Variation 27.92 |
Secondary
Number of Participants With Anti-IMCgp100 Antibody Formation (Dose Escalation and Dose Expansion Parts)
To provide a comprehensive anti-drug antibody (ADA) summary for the study, individual participant data were combined and assessed as distinct groups based on characteristics of their ADA response. Evaluable participants were those with post-drug administration samples. ADA prevalence (pre- existing antibody response) was measured as the number of baseline-positive participant out of all participants who provided baseline samples. Overall ADA incidence was calculated based on the combined number of treatment-boosted and treatment-induced ADA-positive participants. The treatment-induced incidence was determined as the number of ADA- positive participants of those that were ADA-negative at baseline; while treatment-boosted incidence was determined as the number of participants with an ADA titer increase equal to or greater than the minimum significant dilution (3-fold) of the assay.
Time frame: 28 months
Population: Efficacy population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMCgp100 Weekly Dosing Regimen | Number of Participants With Anti-IMCgp100 Antibody Formation (Dose Escalation and Dose Expansion Parts) | 2 participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants With Anti-IMCgp100 Antibody Formation (Dose Escalation and Dose Expansion Parts) | 1 participants |
Secondary
Number of Participants With Best Overall Response Per Response Evaluation Criteria In Solid Tumors (RECIST) (Weekly Dosing-Dose Expansion Part)
The best overall response was assigned as complete response (CR), partial response (PR), minor response, stable disease, progressive disease (PD) or not evaluable (NE) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
Time frame: 28 months
Population: Efficacy population: only evaluable participants (those having both a baseline and post treatment sample).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMCgp100 Weekly Dosing Regimen | Number of Participants With Best Overall Response Per Response Evaluation Criteria In Solid Tumors (RECIST) (Weekly Dosing-Dose Expansion Part) | 5 participants |
| IMCgp100 Daily Dosing Regimen | Number of Participants With Best Overall Response Per Response Evaluation Criteria In Solid Tumors (RECIST) (Weekly Dosing-Dose Expansion Part) | 1 participants |