Neoplasms
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2), Lymphocyte-activation gene 3 (LAG3, LAG-3, CD223)
Brief summary
This is a safety and pharmacokinetics study of favezelimab as monotherapy and in combination with pembrolizumab AND favezelimab/pembrolizumab as monotherapy in adults with metastatic solid tumors for which there is no available therapy which may convey clinical benefit. Part A of this study is a dose escalation design in which participants receive favezelimab as monotherapy or favezelimab in combination with pembrolizumab. Part B is a dose confirmation design to estimate the recommended Phase 2 dose (RP2D), as determined by dose-limiting toxicity, for favezelimab in combination with pembrolizumab or pembrolizumab and lenvatinib in participants with advanced solid tumors. Part B will also assess the efficacy of favezelimab as monotherapy; favezelimab in combination with pembrolizumab with and without chemotherapy; favezelimab in combination with pembrolizumab and lenvatinib; and favezelimab/pembrolizumab as monotherapy in expansion cohorts. Participants who have completed the initial course of treatment and have investigator-determined progressive disease may be eligible for a second course of an additional 17 cycles of study treatment.
Detailed description
All participants who completed the first course were eligible for second course treatment after Sponsor consultation if there was investigator-determined progressive disease after initial treatment had been been completed.
Interventions
BIOLOGICALFavezelimab/Pembrolizumab
IV infusion
BIOLOGICALFavezelimab
IV infusion
BIOLOGICALPembrolizumab
IV infusion
DRUGOxaliplatin
IV infusion
DRUGIrinotecan
IV infusion
DRUGLeucovorin (Calcium Folinate)
IV infusion
DRUGFluorouracil [5-FU]
IV infusion
DRUGLenvatinib
Oral
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants were allocated to arms in a non-random fashion, except in the case of those with gastric cancer enrolled in Part B, who were randomized 1:1 between Arm 2A and Arm 2B (favezelimab 200 mg and 800 mg, respectively). Part B initiated after determination of a favezelimab recommended phase 2 dose (RP2D) from Part A.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Part A and Part B: Has histologically or cytologically-confirmed metastatic solid tumor. * Has measurable disease by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) 1.1 criteria. * Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. * Demonstrates adequate organ function. * If female, is not pregnant or breastfeeding, and if of child-bearing potential, is willing to use an adequate method of contraception for the course of the study and for at least 180 days after the last dose of chemotherapy, 120 days after the last dose of pembrolizumab or favezelimab, or 30 days after the last dose of lenvatinib, whichever occurs last. * If male with a female partner(s) of child-bearing potential, both must agree to use an adequate method of contraception starting with the first dose of study drug through 95 days after the last dose of study drug.
Exclusion criteria
* Has had chemotherapy, radiation or biological cancer therapy within 4 weeks prior to the first dose of study drug, or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 0 or 1 from the AEs due to cancer therapeutics administered more than 4 weeks earlier (this includes participants with previous immunomodulatory therapy with residual immune-related \[ir\]AEs). * Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study drug. * Has received previous treatment with another agent targeting the lymphocyte-activation gene 3 (LAG-3) receptor. * Has received previous treatment with an immunomodulatory therapy (e.g., anti-programmed cell death-1/anti-programmed cell death-ligand 1 \[anti-PD-1/anti-PD-L1\] or cytotoxic T-lymphocyte-associated protein 4 \[CTLA 4\] agent) and was discontinued from that therapy due to a Grade 3 or higher irAE. * Is expected to require any other form of antineoplastic therapy while on study. * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy in excess of replacement doses, or on any other form of immunosuppressive medication. * Has a history of a previous, additional malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for 5 years. Time frame exceptions include successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer, or other in situ cancers. * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. * Has had a severe hypersensitivity reaction to treatment with another monoclonal antibody. * Has an active autoimmune disease or a documented history of autoimmune disease, except vitiligo or resolved childhood asthma/atopy. * Has an active infection requiring therapy. * Has history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. * Has had a prior stem cell or bone marrow transplant. * Has a known history of or screens positive for Human Immunodeficiency Virus (HIV), active chronic or acute Hepatitis B or Hepatitis C. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study. * Is a regular user as determined by investigator judgement (including recreational use) of any illicit drugs or has a recent history (within the last year) of substance abuse (including alcohol), at the time of signing informed consent. * Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible. * Has clinically significant heart disease that affects normal activities. * Has received a live-virus vaccine within 30 days of planned start of study drug. Seasonal flu vaccines that do not contain live virus are permitted.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | Up to 21 days (Cycle 1) | DLTs were assessed during the first cycle (21 days) & were defined as: Grade (Gr) 4 nonhematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days, except Gr 4 thrombocytopenia of any duration or Gr 3 thrombocytopenia associated with bleeding; Gr 3 nonhematologic toxicity lasting ≥3 days despite optimal supportive care (with exceptions); Gr 3 or 4 nonhematologic lab abnormality (if medical intervention was required, lead to hospitalization, or persisted for \>1 week); Gr 3 or 4 febrile neutropenia; any drug-related AE that caused the participant to discontinue treatment during Cycle 1; Grade 5 toxicity; Any treatment-related toxicity that causes ≥2-week delay in initiation of Cycle 2. |
| Number of Participants Who Experienced an Adverse Event (AE) | Up to approximately 31.3 months | An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE is presented. |
| Number of Participants Who Discontinued Study Treatment Due to an AE | Up to approximately 28.3 months | An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study treatment due to an AE is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Serum Concentration (Cmax) of Favezelimab | Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8 | Blood for serum samples was collected at pre-specified time points to determine the Cmax of favezelimab. In addition to time points listed in Time Frame, participants enrolled in mainland China also had samples drawn predose on Day 1 of Cycle 5 and postdose on Day 2 of Cycles 4 and 8. Per protocol, different arms had different sampling schedules and therefore were not analyzed for all cycles. |
| AUC0-inf of Pembrolizumab | Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8 | Blood for serum samples was collected at pre-specified time points to determine the AUC0-inf of pembrolizumab. In addition to time points listed in Time Frame, participants enrolled in mainland China also had samples drawn predose on Day 1 of Cycle 5 and postdose on Day 2 of Cycles 4 and 8. Per protocol, different arms had different sampling schedules and therefore were not analyzed for all cycles. |
| AUC0-21 Days of Pembrolizumab | Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8 | Blood for serum samples was collected at pre-specified time points to determine the AUC0-21 Days of pembrolizumab. In addition to time points listed in Time Frame, participants enrolled in mainland China also had samples drawn predose on Day 1 of Cycle 5 and postdose on Day 2 of Cycles 4 and 8. Per protocol, different arms had different sampling schedules and therefore were not analyzed for all cycles. |
| Cmax of Pembrolizumab | Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8 | Blood for serum samples was collected at pre-specified time points to determine the Cmax of pembrolizumab. In addition to time points listed in Time Frame, participants enrolled in mainland China also had samples drawn predose on Day 1 of Cycle 5 and postdose on Day 2 of Cycles 4 and 8. Per protocol, different arms had different sampling schedules and therefore were not analyzed for all cycles. |
| Objective Response Rate (ORR) for Part B Participants | Up to approximately 92 months | ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experienced a CR or PR is presented. |
| AUC0-inf of Lenvatinib | Up to 4 hours postdose, and between 6-10 hours postdose on Cycle 1 Day 1; Predose and between 2-12 hours postdose on Cycle 1 Day 15; Predose, between 0.5-4 hours postdose, and between 6-10 hours postdose on Cycle 2 Day 1 | Blood for serum samples was collected at pre-specified time points to determine the AUC0-inf of lenvatinib. |
| AUC0-21 Days of Lenvatinib | Up to 4 hours postdose, and between 6-10 hours postdose on Cycle 1 Day 1; Predose and between 2-12 hours postdose on Cycle 1 Day 15; Predose, between 0.5-4 hours postdose, and between 6-10 hours postdose on Cycle 2 Day 1 | Blood for serum samples was collected at pre-specified time points to determine the AUC0-21 Days of lenvatinib. |
| Cmax of Lenvatinib | Up to 4 hours postdose, and between 6-10 hours postdose on Cycle 1 Day 1; Predose and between 2-12 hours postdose on Cycle 1 Day 15; Predose, between 0.5-4 hours postdose, and between 6-10 hours postdose on Cycle 2 Day 1 | Blood for serum samples was collected at pre-specified time points to determine the Cmax of lenvatinib. |
| Predose Serum Concentration of Favezelimab | Predose on Day 1 of cycles 1-4, 6, and 8. Per protocol, different arms had different sampling schedules and therefore were not analyzed for all cycles. | Blood for serum samples was collected at pre-specified time points to determine the predose serum concentration of favezelimab, which is presented. |
| Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8 | Blood for serum samples was collected at pre-specified time points to determine the AUC0-inf of favezelimab. In addition to time points listed in Time Frame, participants enrolled in mainland China also had samples drawn predose on Day 1 of Cycle 5 and postdose on Day 2 of Cycles 4 and 8. Per protocol, different arms had different sampling schedules and therefore were not analyzed for all cycles. |
| Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8 | Blood for serum samples was collected at pre-specified time points to determine the AUC0-21 Days of favezelimab. In addition to time points listed in Time Frame, participants enrolled in mainland China also had samples drawn predose on Day 1 of Cycle 5 and postdose on Day 2 of Cycles 4 and 8. Per protocol, different arms had different sampling schedules and therefore were not analyzed for all cycles. |
Participant flow
Pre-assignment details
One participant received 2 randomization numbers due to an erroneous initial randomization, but is only counted once in Participant Flow due to the rapid correction and drug administration only happening after the correction.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Favezelimab 7 mg Monotherapy Participants received favezelimab 7 mg intravenous (IV) infusion on Day 1 of each 21-day cycle. | 3 |
| Part A: Favezelimab 21 mg Monotherapy Participants received favezelimab 21 mg IV infusion on Day 1 of each 21-day cycle. | 6 |
| Part A: Favezelimab 70 mg Monotherapy Participants received favezelimab 70 mg IV infusion on Day 1 of each 21-day cycle. | 3 |
| Part A: Favezelimab 210 mg Monotherapy Participants received favezelimab 210 mg IV infusion on Day 1 of each 21-day cycle. | 3 |
| Part A: Favezelimab 700 mg Monotherapy Participants received favezelimab 700 mg IV infusion on Day 1 of each 21-day cycle. | 3 |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg Participants received favezelimab 7 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. | 3 |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg Participants received favezelimab 21 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. | 3 |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg Participants received favezelimab 70 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. | 3 |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg Participants received favezelimab 210 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. | 3 |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg Participants received favezelimab 700 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. | 3 |
| Part B: Favezelimab 800 mg Monotherapy (Arm 1) Participants received favezelimab 800 mg monotherapy IV infusion on Day 1 of each 21-day cycle. | 21 |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) Participants received favezelimab 200 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. | 206 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) Participants received favezelimab 700 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. | 40 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) Participants received favezelimab 800 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. | 41 |
| Part B: MK-4280A (Arm 5) Participants received MK-4280A, a coformulation of favezelimab 800 mg + pembrolizumab 200 mg IV infusion on Day 1 of each 21-day cycle. | 59 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) Participants received favezelimab 800 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle PLUS mFOLFOX7 (oxaliplatin 85 mg/m\^2 IV, leucovorin \[calcium folinate\] 400 mg/m\^2 IV, and fluorouracil \[5-FU\] 2400 mg/m\^2 IV over 46 to 48 hours, every 2 weeks \[Q2W\]). | 20 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) Participants received favezelimab 800 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle PLUS FOLFIRI (irinotecan 180 mg/m\^2 IV, leucovorin \[calcium folinate\] 400 mg/m\^2 IV and 5-FU 2400 mg/m\^2 IV over 46 to 48 hours, Q2W). | 21 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) Participants received favezelimab 800 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle PLUS oral lenvatinib 20 mg once daily. | 40 |
| Total | 481 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Death | 1 | 3 | 2 | 1 | 2 | 1 | 2 | 2 | 3 | 1 | 20 | 166 | 34 | 30 | 45 | 16 | 20 | 28 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 2 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Progressive Disease | 2 | 3 | 1 | 1 | 1 | 2 | 1 | 1 | 0 | 1 | 0 | 4 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
| Overall Study | Sponsor Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 3 | 2 | 4 | 4 | 0 | 8 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 27 | 2 | 8 | 7 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Total | Part A: Favezelimab 7 mg Monotherapy | Part A: Favezelimab 21 mg Monotherapy | Part A: Favezelimab 70 mg Monotherapy | Part A: Favezelimab 210 mg Monotherapy | Part A: Favezelimab 700 mg Monotherapy | Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | Part B: Favezelimab 800 mg Monotherapy (Arm 1) | Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Part B: MK-4280A (Arm 5) | Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 58.3 Years STANDARD_DEVIATION 11.05 | 56.3 Years STANDARD_DEVIATION 15.5 | 59.3 Years STANDARD_DEVIATION 10.1 | 68.7 Years STANDARD_DEVIATION 15.3 | 48.7 Years STANDARD_DEVIATION 6.1 | 52.0 Years STANDARD_DEVIATION 14.7 | 54.0 Years STANDARD_DEVIATION 12.2 | 52.3 Years STANDARD_DEVIATION 17.1 | 64.7 Years STANDARD_DEVIATION 7.5 | 55.3 Years STANDARD_DEVIATION 12.4 | 68.7 Years STANDARD_DEVIATION 9.6 | 60.3 Years STANDARD_DEVIATION 10.6 | 58.1 Years STANDARD_DEVIATION 11.2 | 58.5 Years STANDARD_DEVIATION 12 | 57.9 Years STANDARD_DEVIATION 10.9 | 56.3 Years STANDARD_DEVIATION 9.7 | 58.3 Years STANDARD_DEVIATION 12.1 | 59.5 Years STANDARD_DEVIATION 9.9 | 61.1 Years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 58 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 25 Participants | 6 Participants | 8 Participants | 4 Participants | 1 Participants | 7 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 406 Participants | 2 Participants | 5 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 19 Participants | 174 Participants | 33 Participants | 32 Participants | 52 Participants | 19 Participants | 12 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 17 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 7 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 98 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 36 Participants | 11 Participants | 9 Participants | 20 Participants | 7 Participants | 2 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 4 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 356 Participants | 1 Participants | 6 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 19 Participants | 164 Participants | 29 Participants | 31 Participants | 30 Participants | 12 Participants | 17 Participants | 25 Participants |
| Sex: Female, Male Female | 180 Participants | 2 Participants | 4 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 11 Participants | 73 Participants | 15 Participants | 17 Participants | 11 Participants | 5 Participants | 9 Participants | 21 Participants |
| Sex: Female, Male Male | 301 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 10 Participants | 133 Participants | 25 Participants | 24 Participants | 48 Participants | 15 Participants | 12 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 3 | 4 / 6 | 3 / 3 | 1 / 3 | 2 / 3 | 1 / 3 | 2 / 3 | 2 / 3 | 3 / 3 | 2 / 3 | 11 / 21 | 172 / 206 | 35 / 40 | 36 / 41 | 50 / 59 | 16 / 20 | 20 / 21 | 28 / 40 | 9 / 9 | 0 / 1 |
| other Total, other adverse events | 3 / 3 | 5 / 6 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 18 / 20 | 185 / 205 | 39 / 40 | 40 / 41 | 54 / 58 | 20 / 20 | 20 / 20 | 40 / 40 | 7 / 9 | 1 / 1 |
| serious Total, serious adverse events | 1 / 3 | 2 / 6 | 0 / 3 | 1 / 3 | 1 / 3 | 1 / 3 | 0 / 3 | 2 / 3 | 2 / 3 | 2 / 3 | 3 / 20 | 69 / 205 | 17 / 40 | 12 / 41 | 20 / 58 | 9 / 20 | 6 / 20 | 23 / 40 | 1 / 9 | 0 / 1 |
Outcome results
Primary
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study treatment due to an AE is presented.
Time frame: Up to approximately 28.3 months
Population: All participants who received ≥1 dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Favezelimab 7 mg Monotherapy | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Part A: Favezelimab 21 mg Monotherapy | Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Part A: Favezelimab 70 mg Monotherapy | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Part A: Favezelimab 210 mg Monotherapy | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Part A: Favezelimab 700 mg Monotherapy | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | Number of Participants Who Discontinued Study Treatment Due to an AE | 2 Participants |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Part B: Favezelimab 800 mg Monotherapy (Arm 1) | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | Number of Participants Who Discontinued Study Treatment Due to an AE | 22 Participants |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Number of Participants Who Discontinued Study Treatment Due to an AE | 5 Participants |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Number of Participants Who Discontinued Study Treatment Due to an AE | 2 Participants |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Number of Participants Who Discontinued Study Treatment Due to an AE | 6 Participants |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Part B: MK-4280A (Arm 5) | Number of Participants Who Discontinued Study Treatment Due to an AE | 5 Participants |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) | Number of Participants Who Discontinued Study Treatment Due to an AE | 11 Participants |
| Part B: Favezelimab Switch Over to Favezelimab 800 mg + Pembrolizumab 200 mg (Switch Over to Arm 2C) | Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Part B: Second Course Favezelimab 200 mg + Pembrolizumab 200 mg (Second Course Arm 2A) | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
Primary
Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)
DLTs were assessed during the first cycle (21 days) & were defined as: Grade (Gr) 4 nonhematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days, except Gr 4 thrombocytopenia of any duration or Gr 3 thrombocytopenia associated with bleeding; Gr 3 nonhematologic toxicity lasting ≥3 days despite optimal supportive care (with exceptions); Gr 3 or 4 nonhematologic lab abnormality (if medical intervention was required, lead to hospitalization, or persisted for \>1 week); Gr 3 or 4 febrile neutropenia; any drug-related AE that caused the participant to discontinue treatment during Cycle 1; Grade 5 toxicity; Any treatment-related toxicity that causes ≥2-week delay in initiation of Cycle 2.
Time frame: Up to 21 days (Cycle 1)
Population: All participants who received ≥1 dose of study treatment prior to determination of maximum tolerated dose, and were observed for safety for 21 days after their first dose of assigned treatment or experienced a DLT prior to 21 days after their first dose of assigned treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Favezelimab 7 mg Monotherapy | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part A: Favezelimab 21 mg Monotherapy | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part A: Favezelimab 70 mg Monotherapy | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part A: Favezelimab 210 mg Monotherapy | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part A: Favezelimab 700 mg Monotherapy | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part B: Favezelimab 800 mg Monotherapy (Arm 1) | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 1 Participants |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 1 Participants |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 1 Participants |
| Part B: MK-4280A (Arm 5) | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 3 Participants |
Primary
Number of Participants Who Experienced an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE is presented.
Time frame: Up to approximately 31.3 months
Population: All participants who received ≥1 dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Favezelimab 7 mg Monotherapy | Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| Part A: Favezelimab 21 mg Monotherapy | Number of Participants Who Experienced an Adverse Event (AE) | 5 Participants |
| Part A: Favezelimab 70 mg Monotherapy | Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| Part A: Favezelimab 210 mg Monotherapy | Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| Part A: Favezelimab 700 mg Monotherapy | Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| Part B: Favezelimab 800 mg Monotherapy (Arm 1) | Number of Participants Who Experienced an Adverse Event (AE) | 19 Participants |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | Number of Participants Who Experienced an Adverse Event (AE) | 196 Participants |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Number of Participants Who Experienced an Adverse Event (AE) | 40 Participants |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Number of Participants Who Experienced an Adverse Event (AE) | 41 Participants |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Number of Participants Who Experienced an Adverse Event (AE) | 20 Participants |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Number of Participants Who Experienced an Adverse Event (AE) | 20 Participants |
| Part B: MK-4280A (Arm 5) | Number of Participants Who Experienced an Adverse Event (AE) | 55 Participants |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) | Number of Participants Who Experienced an Adverse Event (AE) | 40 Participants |
| Part B: Favezelimab Switch Over to Favezelimab 800 mg + Pembrolizumab 200 mg (Switch Over to Arm 2C) | Number of Participants Who Experienced an Adverse Event (AE) | 7 Participants |
| Part B: Second Course Favezelimab 200 mg + Pembrolizumab 200 mg (Second Course Arm 2A) | Number of Participants Who Experienced an Adverse Event (AE) | 1 Participants |
Secondary
Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab
Blood for serum samples was collected at pre-specified time points to determine the AUC0-21 Days of favezelimab. In addition to time points listed in Time Frame, participants enrolled in mainland China also had samples drawn predose on Day 1 of Cycle 5 and postdose on Day 2 of Cycles 4 and 8. Per protocol, different arms had different sampling schedules and therefore were not analyzed for all cycles.
Time frame: Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8
Population: All participants who complied with the protocol sufficiently to ensure that generated data likely exhibiting the effects of treatment, according to the underlying scientific model
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Favezelimab 7 mg Monotherapy | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 7.29 Day*μg/mL | Geometric Coefficient of Variation 58.4 |
| Part A: Favezelimab 7 mg Monotherapy | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 4 | 9.57 Day*μg/mL | Geometric Coefficient of Variation 21.9 |
| Part A: Favezelimab 7 mg Monotherapy | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 2 | 7.83 Day*μg/mL | Geometric Coefficient of Variation 73.1 |
| Part A: Favezelimab 21 mg Monotherapy | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 37.5 Day*μg/mL | Geometric Coefficient of Variation 41.1 |
| Part A: Favezelimab 21 mg Monotherapy | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 4 | 13.8 Day*μg/mL | Geometric Coefficient of Variation 81 |
| Part A: Favezelimab 21 mg Monotherapy | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 2 | 32.7 Day*μg/mL | Geometric Coefficient of Variation 40.1 |
| Part A: Favezelimab 70 mg Monotherapy | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 4 | 89.6 Day*μg/mL | Geometric Coefficient of Variation 65 |
| Part A: Favezelimab 70 mg Monotherapy | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 96.1 Day*μg/mL | Geometric Coefficient of Variation 39.6 |
| Part A: Favezelimab 70 mg Monotherapy | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 2 | 56.4 Day*μg/mL | Geometric Coefficient of Variation 154.4 |
| Part A: Favezelimab 210 mg Monotherapy | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 2 | 300 Day*μg/mL | Geometric Coefficient of Variation 51.4 |
| Part A: Favezelimab 210 mg Monotherapy | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 4 | 306 Day*μg/mL | Geometric Coefficient of Variation 63.4 |
| Part A: Favezelimab 210 mg Monotherapy | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 285 Day*μg/mL | Geometric Coefficient of Variation 42.8 |
| Part A: Favezelimab 210 mg Monotherapy | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 3 | 241 Day*μg/mL | Geometric Coefficient of Variation 26.4 |
| Part A: Favezelimab 700 mg Monotherapy | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 2 | 321 Day*μg/mL | Geometric Coefficient of Variation 44.9 |
| Part A: Favezelimab 700 mg Monotherapy | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 353 Day*μg/mL | Geometric Coefficient of Variation 38.4 |
| Part A: Favezelimab 700 mg Monotherapy | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 4 | 174 Day*μg/mL | Geometric Coefficient of Variation 91 |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 4 | 1620 Day*μg/mL | Geometric Coefficient of Variation 44.2 |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 3 | 1770 Day*μg/mL | — |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 1300 Day*μg/mL | Geometric Coefficient of Variation 34.1 |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 2 | 1480 Day*μg/mL | Geometric Coefficient of Variation 43 |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 8 | 1730 Day*μg/mL | Geometric Coefficient of Variation 51.8 |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 4 | 1710 Day*μg/mL | Geometric Coefficient of Variation 53.6 |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 2 | 1570 Day*μg/mL | Geometric Coefficient of Variation 54.9 |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 1430 Day*μg/mL | Geometric Coefficient of Variation 48.1 |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 3 | 2330 Day*μg/mL | Geometric Coefficient of Variation 51.5 |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 11.0 Day*μg/mL | Geometric Coefficient of Variation 38.6 |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 2 | 9.32 Day*μg/mL | Geometric Coefficient of Variation 184.6 |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 36.5 Day*μg/mL | Geometric Coefficient of Variation 42.4 |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 2 | 32.7 Day*μg/mL | Geometric Coefficient of Variation 40.1 |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 97.2 Day*μg/mL | Geometric Coefficient of Variation 28.5 |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 4 | 53.1 Day*μg/mL | — |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 2 | 59.3 Day*μg/mL | Geometric Coefficient of Variation 88.6 |
| Part B: Favezelimab 800 mg Monotherapy (Arm 1) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 333 Day*μg/mL | Geometric Coefficient of Variation 49.6 |
| Part B: Favezelimab 800 mg Monotherapy (Arm 1) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 2 | 292 Day*μg/mL | Geometric Coefficient of Variation 48.3 |
| Part B: Favezelimab 800 mg Monotherapy (Arm 1) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 4 | 124 Day*μg/mL | Geometric Coefficient of Variation 83.4 |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 2 | 1470 Day*μg/mL | Geometric Coefficient of Variation 15.7 |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 1440 Day*μg/mL | Geometric Coefficient of Variation 23.2 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 2 | 2140 Day*μg/mL | Geometric Coefficient of Variation 40.9 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 1550 Day*μg/mL | Geometric Coefficient of Variation 35.8 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 4 | 2320 Day*μg/mL | Geometric Coefficient of Variation 34.6 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 3 | 2330 Day*μg/mL | Geometric Coefficient of Variation 51.5 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 2 | 6.97 Day*μg/mL | Geometric Coefficient of Variation 25.7 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 4 | 9.57 Day*μg/mL | Geometric Coefficient of Variation 21.9 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 4.82 Day*μg/mL | Geometric Coefficient of Variation 28.5 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 39.6 Day*μg/mL | Geometric Coefficient of Variation 47.7 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 4 | 13.8 Day*μg/mL | Geometric Coefficient of Variation 81 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 95.0 Day*μg/mL | Geometric Coefficient of Variation 57.5 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 4 | 116 Day*μg/mL | Geometric Coefficient of Variation 58.6 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 2 | 53.7 Day*μg/mL | Geometric Coefficient of Variation 327.1 |
| Part B: MK-4280A (Arm 5) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 2 | 300 Day*μg/mL | Geometric Coefficient of Variation 51.4 |
| Part B: MK-4280A (Arm 5) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 4 | 306 Day*μg/mL | Geometric Coefficient of Variation 63.4 |
| Part B: MK-4280A (Arm 5) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 3 | 241 Day*μg/mL | Geometric Coefficient of Variation 26.4 |
| Part B: MK-4280A (Arm 5) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 285 Day*μg/mL | Geometric Coefficient of Variation 42.8 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 4 | 341 Day*μg/mL | — |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 2 | 353 Day*μg/mL | Geometric Coefficient of Variation 49.8 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 374 Day*μg/mL | Geometric Coefficient of Variation 34.9 |
| Part B: Favezelimab Switch Over to Favezelimab 800 mg + Pembrolizumab 200 mg (Switch Over to Arm 2C) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 2 | 1640 Day*μg/mL | Geometric Coefficient of Variation 38.7 |
| Part B: Favezelimab Switch Over to Favezelimab 800 mg + Pembrolizumab 200 mg (Switch Over to Arm 2C) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 4 | 1120 Day*μg/mL | — |
| Part B: Favezelimab Switch Over to Favezelimab 800 mg + Pembrolizumab 200 mg (Switch Over to Arm 2C) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 1370 Day*μg/mL | Geometric Coefficient of Variation 30 |
| Part B: Second Course Favezelimab 200 mg + Pembrolizumab 200 mg (Second Course Arm 2A) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 2 | 1460 Day*μg/mL | Geometric Coefficient of Variation 46 |
| Part B: Second Course Favezelimab 200 mg + Pembrolizumab 200 mg (Second Course Arm 2A) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 3 | 1770 Day*μg/mL | — |
| Part B: Second Course Favezelimab 200 mg + Pembrolizumab 200 mg (Second Course Arm 2A) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 4 | 1670 Day*μg/mL | Geometric Coefficient of Variation 44.6 |
| Part B: Second Course Favezelimab 200 mg + Pembrolizumab 200 mg (Second Course Arm 2A) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 1290 Day*μg/mL | Geometric Coefficient of Variation 35.5 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 2 | 1260 Day*μg/mL | Geometric Coefficient of Variation 65.1 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 1330 Day*μg/mL | Geometric Coefficient of Variation 40.5 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 4 | 1500 Day*μg/mL | Geometric Coefficient of Variation 37.7 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 2 | 1820 Day*μg/mL | Geometric Coefficient of Variation 37.2 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 4 | 2070 Day*μg/mL | Geometric Coefficient of Variation 40.4 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 1420 Day*μg/mL | Geometric Coefficient of Variation 34.8 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 1640 Day*μg/mL | Geometric Coefficient of Variation 71.9 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 2 | 2050 Day*μg/mL | Geometric Coefficient of Variation 43.6 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 4 | 2330 Day*μg/mL | Geometric Coefficient of Variation 90.1 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 1630 Day*μg/mL | Geometric Coefficient of Variation 41.6 |
| Part B: MK-4280A (Arm 5) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 1 | 1290 Day*μg/mL | Geometric Coefficient of Variation 43.7 |
| Part B: MK-4280A (Arm 5) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 8 | 1730 Day*μg/mL | Geometric Coefficient of Variation 51.8 |
| Part B: MK-4280A (Arm 5) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 4 | 1490 Day*μg/mL | Geometric Coefficient of Variation 53.7 |
| Part B: MK-4280A (Arm 5) | Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab | Cycle 2 | 1400 Day*μg/mL | Geometric Coefficient of Variation 51.9 |
Secondary
Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab
Blood for serum samples was collected at pre-specified time points to determine the AUC0-inf of favezelimab. In addition to time points listed in Time Frame, participants enrolled in mainland China also had samples drawn predose on Day 1 of Cycle 5 and postdose on Day 2 of Cycles 4 and 8. Per protocol, different arms had different sampling schedules and therefore were not analyzed for all cycles.
Time frame: Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8
Population: All participants who complied with the protocol sufficiently to ensure that generated data likely exhibiting the effects of treatment, according to the underlying scientific model
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Favezelimab 7 mg Monotherapy | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 7.12 Day*μg/mL | Geometric Coefficient of Variation 58.8 |
| Part A: Favezelimab 7 mg Monotherapy | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 4 | 9.38 Day*μg/mL | Geometric Coefficient of Variation 22.3 |
| Part A: Favezelimab 7 mg Monotherapy | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 2 | 8.28 Day*μg/mL | Geometric Coefficient of Variation 45.8 |
| Part A: Favezelimab 21 mg Monotherapy | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 2 | 33.1 Day*μg/mL | Geometric Coefficient of Variation 41.3 |
| Part A: Favezelimab 21 mg Monotherapy | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 34.6 Day*μg/mL | Geometric Coefficient of Variation 45.4 |
| Part A: Favezelimab 21 mg Monotherapy | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 4 | 13.7 Day*μg/mL | Geometric Coefficient of Variation 79.5 |
| Part A: Favezelimab 70 mg Monotherapy | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 2 | 56.0 Day*μg/mL | Geometric Coefficient of Variation 179.4 |
| Part A: Favezelimab 70 mg Monotherapy | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 98.8 Day*μg/mL | Geometric Coefficient of Variation 42.7 |
| Part A: Favezelimab 70 mg Monotherapy | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 4 | 88.2 Day*μg/mL | Geometric Coefficient of Variation 80.4 |
| Part A: Favezelimab 210 mg Monotherapy | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 305 Day*μg/mL | Geometric Coefficient of Variation 48.4 |
| Part A: Favezelimab 210 mg Monotherapy | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 3 | 248 Day*μg/mL | Geometric Coefficient of Variation 33.6 |
| Part A: Favezelimab 210 mg Monotherapy | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 2 | 330 Day*μg/mL | Geometric Coefficient of Variation 58.1 |
| Part A: Favezelimab 210 mg Monotherapy | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 4 | 329 Day*μg/mL | Geometric Coefficient of Variation 71.5 |
| Part A: Favezelimab 700 mg Monotherapy | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 2 | 335 Day*μg/mL | Geometric Coefficient of Variation 48.5 |
| Part A: Favezelimab 700 mg Monotherapy | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 365 Day*μg/mL | Geometric Coefficient of Variation 39.8 |
| Part A: Favezelimab 700 mg Monotherapy | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 4 | 166 Day*μg/mL | Geometric Coefficient of Variation 114.5 |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 3 | 2000 Day*μg/mL | — |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 1480 Day*μg/mL | Geometric Coefficient of Variation 39.6 |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 2 | 1730 Day*μg/mL | Geometric Coefficient of Variation 53.1 |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 4 | 1870 Day*μg/mL | Geometric Coefficient of Variation 56.5 |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 1620 Day*μg/mL | Geometric Coefficient of Variation 54.7 |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 8 | 2030 Day*μg/mL | Geometric Coefficient of Variation 67.6 |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 3 | 3880 Day*μg/mL | Geometric Coefficient of Variation 16.9 |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 2 | 1850 Day*μg/mL | Geometric Coefficient of Variation 59.2 |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 4 | 1860 Day*μg/mL | Geometric Coefficient of Variation 58.6 |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 10.5 Day*μg/mL | Geometric Coefficient of Variation 49 |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 2 | 14.6 Day*μg/mL | — |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 2 | 33.1 Day*μg/mL | Geometric Coefficient of Variation 41.3 |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 37.4 Day*μg/mL | Geometric Coefficient of Variation 43.3 |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 2 | 60.0 Day*μg/mL | Geometric Coefficient of Variation 92.4 |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 4 | 46.1 Day*μg/mL | — |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 99.3 Day*μg/mL | Geometric Coefficient of Variation 28.6 |
| Part B: Favezelimab 800 mg Monotherapy (Arm 1) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 4 | 113 Day*μg/mL | Geometric Coefficient of Variation 109.9 |
| Part B: Favezelimab 800 mg Monotherapy (Arm 1) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 2 | 298 Day*μg/mL | Geometric Coefficient of Variation 51.6 |
| Part B: Favezelimab 800 mg Monotherapy (Arm 1) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 341 Day*μg/mL | Geometric Coefficient of Variation 51 |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 1590 Day*μg/mL | Geometric Coefficient of Variation 21.5 |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 2 | 1640 Day*μg/mL | Geometric Coefficient of Variation 20.5 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 2 | 2200 Day*μg/mL | Geometric Coefficient of Variation 42.8 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 1820 Day*μg/mL | Geometric Coefficient of Variation 46.6 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 3 | 3880 Day*μg/mL | Geometric Coefficient of Variation 16.8 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 4 | 2880 Day*μg/mL | Geometric Coefficient of Variation 55.2 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 2 | 6.86 Day*μg/mL | Geometric Coefficient of Variation 27.3 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 4.81 Day*μg/mL | Geometric Coefficient of Variation 25.7 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 4 | 9.38 Day*μg/mL | Geometric Coefficient of Variation 22.3 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 21.5 Day*μg/mL | — |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 4 | 13.7 Day*μg/mL | Geometric Coefficient of Variation 79.5 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 4 | 122 Day*μg/mL | Geometric Coefficient of Variation 66.4 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 2 | 52.2 Day*μg/mL | Geometric Coefficient of Variation 429.4 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 98.3 Day*μg/mL | Geometric Coefficient of Variation 63.7 |
| Part B: MK-4280A (Arm 5) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 305 Day*μg/mL | Geometric Coefficient of Variation 48.3 |
| Part B: MK-4280A (Arm 5) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 2 | 324 Day*μg/mL | Geometric Coefficient of Variation 58.7 |
| Part B: MK-4280A (Arm 5) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 3 | 248 Day*μg/mL | Geometric Coefficient of Variation 33.6 |
| Part B: MK-4280A (Arm 5) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 4 | 330 Day*μg/mL | Geometric Coefficient of Variation 70.6 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 2 | 378 Day*μg/mL | Geometric Coefficient of Variation 53.1 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 391 Day*μg/mL | Geometric Coefficient of Variation 36.1 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 4 | 357 Day*μg/mL | — |
| Part B: Favezelimab Switch Over to Favezelimab 800 mg + Pembrolizumab 200 mg (Switch Over to Arm 2C) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 2 | 2330 Day*μg/mL | Geometric Coefficient of Variation 18.4 |
| Part B: Favezelimab Switch Over to Favezelimab 800 mg + Pembrolizumab 200 mg (Switch Over to Arm 2C) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 4 | 1240 Day*μg/mL | — |
| Part B: Favezelimab Switch Over to Favezelimab 800 mg + Pembrolizumab 200 mg (Switch Over to Arm 2C) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 1610 Day*μg/mL | Geometric Coefficient of Variation 36.5 |
| Part B: Second Course Favezelimab 200 mg + Pembrolizumab 200 mg (Second Course Arm 2A) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 3 | 2000 Day*μg/mL | — |
| Part B: Second Course Favezelimab 200 mg + Pembrolizumab 200 mg (Second Course Arm 2A) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 4 | 1940 Day*μg/mL | Geometric Coefficient of Variation 57.5 |
| Part B: Second Course Favezelimab 200 mg + Pembrolizumab 200 mg (Second Course Arm 2A) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 1440 Day*μg/mL | Geometric Coefficient of Variation 41.6 |
| Part B: Second Course Favezelimab 200 mg + Pembrolizumab 200 mg (Second Course Arm 2A) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 2 | 1690 Day*μg/mL | Geometric Coefficient of Variation 57.4 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 1430 Day*μg/mL | Geometric Coefficient of Variation 46.4 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 4 | 1570 Day*μg/mL | Geometric Coefficient of Variation 40.7 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 2 | 1450 Day*μg/mL | Geometric Coefficient of Variation 49.9 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 1670 Day*μg/mL | Geometric Coefficient of Variation 40.3 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 2 | 2300 Day*μg/mL | Geometric Coefficient of Variation 46.6 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 4 | 2370 Day*μg/mL | Geometric Coefficient of Variation 44.6 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 1870 Day*μg/mL | Geometric Coefficient of Variation 75.1 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 2 | 2690 Day*μg/mL | Geometric Coefficient of Variation 55 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 2010 Day*μg/mL | Geometric Coefficient of Variation 54.5 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 4 | 2070 Day*μg/mL | Geometric Coefficient of Variation 73.8 |
| Part B: MK-4280A (Arm 5) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 8 | 2030 Day*μg/mL | Geometric Coefficient of Variation 67.6 |
| Part B: MK-4280A (Arm 5) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 4 | 1640 Day*μg/mL | Geometric Coefficient of Variation 62.4 |
| Part B: MK-4280A (Arm 5) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 2 | 1580 Day*μg/mL | Geometric Coefficient of Variation 61.9 |
| Part B: MK-4280A (Arm 5) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab | Cycle 1 | 1430 Day*μg/mL | Geometric Coefficient of Variation 49.6 |
Secondary
AUC0-21 Days of Lenvatinib
Blood for serum samples was collected at pre-specified time points to determine the AUC0-21 Days of lenvatinib.
Time frame: Up to 4 hours postdose, and between 6-10 hours postdose on Cycle 1 Day 1; Predose and between 2-12 hours postdose on Cycle 1 Day 15; Predose, between 0.5-4 hours postdose, and between 6-10 hours postdose on Cycle 2 Day 1
Population: All participants who received ≥1 dose of lenvatinib and complied with the protocol sufficiently to ensure that generated data likely exhibiting the effects of treatment, according to the underlying scientific model
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: Favezelimab 7 mg Monotherapy | AUC0-21 Days of Lenvatinib | Cycle 1 | NA Day*ng/mL |
| Part A: Favezelimab 7 mg Monotherapy | AUC0-21 Days of Lenvatinib | Cycle 2 | NA Day*ng/mL |
Secondary
AUC0-21 Days of Pembrolizumab
Blood for serum samples was collected at pre-specified time points to determine the AUC0-21 Days of pembrolizumab. In addition to time points listed in Time Frame, participants enrolled in mainland China also had samples drawn predose on Day 1 of Cycle 5 and postdose on Day 2 of Cycles 4 and 8. Per protocol, different arms had different sampling schedules and therefore were not analyzed for all cycles.
Time frame: Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8
Population: All participants who complied with the protocol sufficiently to ensure that generated data likely exhibiting the effects of treatment, according to the underlying scientific model
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Favezelimab 7 mg Monotherapy | AUC0-21 Days of Pembrolizumab | Cycle 4 | 692 Day*μg/mL | Geometric Coefficient of Variation 39.3 |
| Part A: Favezelimab 7 mg Monotherapy | AUC0-21 Days of Pembrolizumab | Cycle 8 | 1040 Day*μg/mL | Geometric Coefficient of Variation 37.5 |
| Part A: Favezelimab 7 mg Monotherapy | AUC0-21 Days of Pembrolizumab | Cycle 3 | 543 Day*μg/mL | Geometric Coefficient of Variation 38.7 |
| Part A: Favezelimab 7 mg Monotherapy | AUC0-21 Days of Pembrolizumab | Cycle 1 | 427 Day*μg/mL | Geometric Coefficient of Variation 31.5 |
| Part A: Favezelimab 7 mg Monotherapy | AUC0-21 Days of Pembrolizumab | Cycle 2 | 561 Day*μg/mL | Geometric Coefficient of Variation 38 |
| Part A: Favezelimab 21 mg Monotherapy | AUC0-21 Days of Pembrolizumab | Cycle 2 | 615 Day*μg/mL | Geometric Coefficient of Variation 16.8 |
| Part A: Favezelimab 21 mg Monotherapy | AUC0-21 Days of Pembrolizumab | Cycle 1 | 418 Day*μg/mL | Geometric Coefficient of Variation 13 |
| Part A: Favezelimab 21 mg Monotherapy | AUC0-21 Days of Pembrolizumab | Cycle 4 | 805 Day*μg/mL | Geometric Coefficient of Variation 5 |
| Part A: Favezelimab 70 mg Monotherapy | AUC0-21 Days of Pembrolizumab | Cycle 2 | 504 Day*μg/mL | Geometric Coefficient of Variation 88.8 |
| Part A: Favezelimab 70 mg Monotherapy | AUC0-21 Days of Pembrolizumab | Cycle 4 | 403 Day*μg/mL | Geometric Coefficient of Variation 74.6 |
| Part A: Favezelimab 70 mg Monotherapy | AUC0-21 Days of Pembrolizumab | Cycle 1 | 485 Day*μg/mL | Geometric Coefficient of Variation 49 |
| Part A: Favezelimab 210 mg Monotherapy | AUC0-21 Days of Pembrolizumab | Cycle 2 | 597 Day*μg/mL | Geometric Coefficient of Variation 38.3 |
| Part A: Favezelimab 210 mg Monotherapy | AUC0-21 Days of Pembrolizumab | Cycle 1 | 382 Day*μg/mL | Geometric Coefficient of Variation 36.7 |
| Part A: Favezelimab 210 mg Monotherapy | AUC0-21 Days of Pembrolizumab | Cycle 4 | 1050 Day*μg/mL | Geometric Coefficient of Variation 79.9 |
| Part A: Favezelimab 700 mg Monotherapy | AUC0-21 Days of Pembrolizumab | Cycle 4 | 670 Day*μg/mL | Geometric Coefficient of Variation 36.4 |
| Part A: Favezelimab 700 mg Monotherapy | AUC0-21 Days of Pembrolizumab | Cycle 3 | 537 Day*μg/mL | Geometric Coefficient of Variation 40.1 |
| Part A: Favezelimab 700 mg Monotherapy | AUC0-21 Days of Pembrolizumab | Cycle 1 | 412 Day*μg/mL | Geometric Coefficient of Variation 31.1 |
| Part A: Favezelimab 700 mg Monotherapy | AUC0-21 Days of Pembrolizumab | Cycle 2 | 545 Day*μg/mL | Geometric Coefficient of Variation 36.6 |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | AUC0-21 Days of Pembrolizumab | Cycle 2 | 662 Day*μg/mL | Geometric Coefficient of Variation 57.6 |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | AUC0-21 Days of Pembrolizumab | Cycle 4 | 701 Day*μg/mL | — |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | AUC0-21 Days of Pembrolizumab | Cycle 1 | 556 Day*μg/mL | Geometric Coefficient of Variation 15.2 |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | AUC0-21 Days of Pembrolizumab | Cycle 1 | 410 Day*μg/mL | Geometric Coefficient of Variation 30 |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | AUC0-21 Days of Pembrolizumab | Cycle 2 | 487 Day*μg/mL | Geometric Coefficient of Variation 27.9 |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | AUC0-21 Days of Pembrolizumab | Cycle 4 | 416 Day*μg/mL | Geometric Coefficient of Variation 15.7 |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | AUC0-21 Days of Pembrolizumab | Cycle 3 | 577 Day*μg/mL | Geometric Coefficient of Variation 43.9 |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | AUC0-21 Days of Pembrolizumab | Cycle 2 | 588 Day*μg/mL | Geometric Coefficient of Variation 35.4 |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | AUC0-21 Days of Pembrolizumab | Cycle 4 | 754 Day*μg/mL | Geometric Coefficient of Variation 45.4 |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | AUC0-21 Days of Pembrolizumab | Cycle 1 | 422 Day*μg/mL | Geometric Coefficient of Variation 28.5 |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | AUC0-21 Days of Pembrolizumab | Cycle 1 | 427 Day*μg/mL | Geometric Coefficient of Variation 25.2 |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | AUC0-21 Days of Pembrolizumab | Cycle 4 | 664 Day*μg/mL | Geometric Coefficient of Variation 31.9 |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | AUC0-21 Days of Pembrolizumab | Cycle 2 | 553 Day*μg/mL | Geometric Coefficient of Variation 25.1 |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | AUC0-21 Days of Pembrolizumab | Cycle 4 | 769 Day*μg/mL | Geometric Coefficient of Variation 21.3 |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | AUC0-21 Days of Pembrolizumab | Cycle 2 | 618 Day*μg/mL | Geometric Coefficient of Variation 22.9 |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | AUC0-21 Days of Pembrolizumab | Cycle 1 | 431 Day*μg/mL | Geometric Coefficient of Variation 24 |
| Part B: Favezelimab 800 mg Monotherapy (Arm 1) | AUC0-21 Days of Pembrolizumab | Cycle 1 | 489 Day*μg/mL | Geometric Coefficient of Variation 39.3 |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | AUC0-21 Days of Pembrolizumab | Cycle 1 | 447 Day*μg/mL | Geometric Coefficient of Variation 32.8 |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | AUC0-21 Days of Pembrolizumab | Cycle 2 | 621 Day*μg/mL | Geometric Coefficient of Variation 32.4 |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | AUC0-21 Days of Pembrolizumab | Cycle 4 | 727 Day*μg/mL | Geometric Coefficient of Variation 36.7 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | AUC0-21 Days of Pembrolizumab | Cycle 8 | 1040 Day*μg/mL | Geometric Coefficient of Variation 37.5 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | AUC0-21 Days of Pembrolizumab | Cycle 2 | 547 Day*μg/mL | Geometric Coefficient of Variation 56.9 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | AUC0-21 Days of Pembrolizumab | Cycle 4 | 705 Day*μg/mL | Geometric Coefficient of Variation 45.7 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | AUC0-21 Days of Pembrolizumab | Cycle 1 | 427 Day*μg/mL | Geometric Coefficient of Variation 34.2 |
Secondary
AUC0-inf of Lenvatinib
Blood for serum samples was collected at pre-specified time points to determine the AUC0-inf of lenvatinib.
Time frame: Up to 4 hours postdose, and between 6-10 hours postdose on Cycle 1 Day 1; Predose and between 2-12 hours postdose on Cycle 1 Day 15; Predose, between 0.5-4 hours postdose, and between 6-10 hours postdose on Cycle 2 Day 1
Population: All participants who received ≥1 dose of lenvatinib and complied with the protocol sufficiently to ensure that generated data likely exhibiting the effects of treatment, according to the underlying scientific model
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: Favezelimab 7 mg Monotherapy | AUC0-inf of Lenvatinib | Cycle 2 | NA Day*ng/mL |
| Part A: Favezelimab 7 mg Monotherapy | AUC0-inf of Lenvatinib | Cycle 1 | NA Day*ng/mL |
Secondary
AUC0-inf of Pembrolizumab
Blood for serum samples was collected at pre-specified time points to determine the AUC0-inf of pembrolizumab. In addition to time points listed in Time Frame, participants enrolled in mainland China also had samples drawn predose on Day 1 of Cycle 5 and postdose on Day 2 of Cycles 4 and 8. Per protocol, different arms had different sampling schedules and therefore were not analyzed for all cycles.
Time frame: Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8
Population: All participants who complied with the protocol sufficiently to ensure that generated data likely exhibiting the effects of treatment, according to the underlying scientific model
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Favezelimab 7 mg Monotherapy | AUC0-inf of Pembrolizumab | Cycle 4 | 903 Day*μg/mL | Geometric Coefficient of Variation 49.2 |
| Part A: Favezelimab 7 mg Monotherapy | AUC0-inf of Pembrolizumab | Cycle 2 | 843 Day*μg/mL | Geometric Coefficient of Variation 52.1 |
| Part A: Favezelimab 7 mg Monotherapy | AUC0-inf of Pembrolizumab | Cycle 1 | 586 Day*μg/mL | Geometric Coefficient of Variation 38.9 |
| Part A: Favezelimab 7 mg Monotherapy | AUC0-inf of Pembrolizumab | Cycle 8 | 1980 Day*μg/mL | Geometric Coefficient of Variation 54.8 |
| Part A: Favezelimab 7 mg Monotherapy | AUC0-inf of Pembrolizumab | Cycle 3 | 846 Day*μg/mL | Geometric Coefficient of Variation 98 |
| Part A: Favezelimab 21 mg Monotherapy | AUC0-inf of Pembrolizumab | Cycle 1 | 662 Day*μg/mL | Geometric Coefficient of Variation 20.7 |
| Part A: Favezelimab 21 mg Monotherapy | AUC0-inf of Pembrolizumab | Cycle 4 | 1190 Day*μg/mL | Geometric Coefficient of Variation 17 |
| Part A: Favezelimab 21 mg Monotherapy | AUC0-inf of Pembrolizumab | Cycle 2 | 1060 Day*μg/mL | Geometric Coefficient of Variation 22.4 |
| Part A: Favezelimab 70 mg Monotherapy | AUC0-inf of Pembrolizumab | Cycle 4 | 503 Day*μg/mL | Geometric Coefficient of Variation 101.3 |
| Part A: Favezelimab 70 mg Monotherapy | AUC0-inf of Pembrolizumab | Cycle 1 | 332 Day*μg/mL | — |
| Part A: Favezelimab 70 mg Monotherapy | AUC0-inf of Pembrolizumab | Cycle 2 | 613 Day*μg/mL | Geometric Coefficient of Variation 100.5 |
| Part A: Favezelimab 210 mg Monotherapy | AUC0-inf of Pembrolizumab | Cycle 1 | 612 Day*μg/mL | Geometric Coefficient of Variation 40.8 |
| Part A: Favezelimab 210 mg Monotherapy | AUC0-inf of Pembrolizumab | Cycle 2 | 940 Day*μg/mL | Geometric Coefficient of Variation 46.3 |
| Part A: Favezelimab 210 mg Monotherapy | AUC0-inf of Pembrolizumab | Cycle 4 | 3650 Day*μg/mL | Geometric Coefficient of Variation 181.2 |
| Part A: Favezelimab 700 mg Monotherapy | AUC0-inf of Pembrolizumab | Cycle 4 | 894 Day*μg/mL | Geometric Coefficient of Variation 47.9 |
| Part A: Favezelimab 700 mg Monotherapy | AUC0-inf of Pembrolizumab | Cycle 2 | 807 Day*μg/mL | Geometric Coefficient of Variation 50.6 |
| Part A: Favezelimab 700 mg Monotherapy | AUC0-inf of Pembrolizumab | Cycle 3 | 878 Day*μg/mL | Geometric Coefficient of Variation 72.1 |
| Part A: Favezelimab 700 mg Monotherapy | AUC0-inf of Pembrolizumab | Cycle 1 | 564 Day*μg/mL | Geometric Coefficient of Variation 40.8 |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | AUC0-inf of Pembrolizumab | Cycle 1 | 821 Day*μg/mL | Geometric Coefficient of Variation 18.2 |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | AUC0-inf of Pembrolizumab | Cycle 2 | 727 Day*μg/mL | Geometric Coefficient of Variation 67.2 |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | AUC0-inf of Pembrolizumab | Cycle 4 | 962 Day*μg/mL | — |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | AUC0-inf of Pembrolizumab | Cycle 2 | 847 Day*μg/mL | Geometric Coefficient of Variation 23.2 |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | AUC0-inf of Pembrolizumab | Cycle 4 | 528 Day*μg/mL | Geometric Coefficient of Variation 43 |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | AUC0-inf of Pembrolizumab | Cycle 1 | 543 Day*μg/mL | Geometric Coefficient of Variation 27.4 |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | AUC0-inf of Pembrolizumab | Cycle 3 | 1990 Day*μg/mL | — |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | AUC0-inf of Pembrolizumab | Cycle 4 | 997 Day*μg/mL | Geometric Coefficient of Variation 56.6 |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | AUC0-inf of Pembrolizumab | Cycle 2 | 877 Day*μg/mL | Geometric Coefficient of Variation 53.7 |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | AUC0-inf of Pembrolizumab | Cycle 1 | 586 Day*μg/mL | Geometric Coefficient of Variation 39.1 |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | AUC0-inf of Pembrolizumab | Cycle 1 | 589 Day*μg/mL | Geometric Coefficient of Variation 34.4 |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | AUC0-inf of Pembrolizumab | Cycle 2 | 812 Day*μg/mL | Geometric Coefficient of Variation 41.4 |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | AUC0-inf of Pembrolizumab | Cycle 4 | 848 Day*μg/mL | Geometric Coefficient of Variation 37.8 |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | AUC0-inf of Pembrolizumab | Cycle 1 | 626 Day*μg/mL | Geometric Coefficient of Variation 26.7 |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | AUC0-inf of Pembrolizumab | Cycle 2 | 1150 Day*μg/mL | Geometric Coefficient of Variation 59.8 |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | AUC0-inf of Pembrolizumab | Cycle 4 | 1000 Day*μg/mL | Geometric Coefficient of Variation 21.6 |
| Part B: Favezelimab 800 mg Monotherapy (Arm 1) | AUC0-inf of Pembrolizumab | Cycle 1 | 623 Day*μg/mL | Geometric Coefficient of Variation 44.6 |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | AUC0-inf of Pembrolizumab | Cycle 4 | 929 Day*μg/mL | Geometric Coefficient of Variation 35.7 |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | AUC0-inf of Pembrolizumab | Cycle 1 | 661 Day*μg/mL | Geometric Coefficient of Variation 32.9 |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | AUC0-inf of Pembrolizumab | Cycle 2 | 1100 Day*μg/mL | Geometric Coefficient of Variation 48.8 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | AUC0-inf of Pembrolizumab | Cycle 8 | 1970 Day*μg/mL | Geometric Coefficient of Variation 55 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | AUC0-inf of Pembrolizumab | Cycle 2 | 861 Day*μg/mL | Geometric Coefficient of Variation 75.4 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | AUC0-inf of Pembrolizumab | Cycle 4 | 1040 Day*μg/mL | Geometric Coefficient of Variation 73 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | AUC0-inf of Pembrolizumab | Cycle 1 | 619 Day*μg/mL | Geometric Coefficient of Variation 41.3 |
Secondary
Cmax of Lenvatinib
Blood for serum samples was collected at pre-specified time points to determine the Cmax of lenvatinib.
Time frame: Up to 4 hours postdose, and between 6-10 hours postdose on Cycle 1 Day 1; Predose and between 2-12 hours postdose on Cycle 1 Day 15; Predose, between 0.5-4 hours postdose, and between 6-10 hours postdose on Cycle 2 Day 1
Population: All participants who received ≥1 dose of lenvatinib and complied with the protocol sufficiently to ensure that generated data likely exhibiting the effects of treatment, according to the underlying scientific model
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: Favezelimab 7 mg Monotherapy | Cmax of Lenvatinib | Cycle 1 | NA ng/mL |
| Part A: Favezelimab 7 mg Monotherapy | Cmax of Lenvatinib | Cycle 2 | NA ng/mL |
Secondary
Cmax of Pembrolizumab
Blood for serum samples was collected at pre-specified time points to determine the Cmax of pembrolizumab. In addition to time points listed in Time Frame, participants enrolled in mainland China also had samples drawn predose on Day 1 of Cycle 5 and postdose on Day 2 of Cycles 4 and 8. Per protocol, different arms had different sampling schedules and therefore were not analyzed for all cycles.
Time frame: Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8
Population: All participants who complied with the protocol sufficiently to ensure that generated data likely exhibiting the effects of treatment, according to the underlying scientific model
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Favezelimab 7 mg Monotherapy | Cmax of Pembrolizumab | Cycle 1 | 59.6 μg/mL | Geometric Coefficient of Variation 29.6 |
| Part A: Favezelimab 7 mg Monotherapy | Cmax of Pembrolizumab | Cycle 4 | 76.1 μg/mL | Geometric Coefficient of Variation 30.2 |
| Part A: Favezelimab 7 mg Monotherapy | Cmax of Pembrolizumab | Cycle 3 | 36.4 μg/mL | Geometric Coefficient of Variation 41.9 |
| Part A: Favezelimab 7 mg Monotherapy | Cmax of Pembrolizumab | Cycle 2 | 67.5 μg/mL | Geometric Coefficient of Variation 34.3 |
| Part A: Favezelimab 7 mg Monotherapy | Cmax of Pembrolizumab | Cycle 8 | 93.8 μg/mL | Geometric Coefficient of Variation 25.8 |
| Part A: Favezelimab 21 mg Monotherapy | Cmax of Pembrolizumab | Cycle 4 | 79.6 μg/mL | Geometric Coefficient of Variation 7.8 |
| Part A: Favezelimab 21 mg Monotherapy | Cmax of Pembrolizumab | Cycle 2 | 65.6 μg/mL | Geometric Coefficient of Variation 21.2 |
| Part A: Favezelimab 21 mg Monotherapy | Cmax of Pembrolizumab | Cycle 1 | 58.5 μg/mL | Geometric Coefficient of Variation 14.9 |
| Part A: Favezelimab 70 mg Monotherapy | Cmax of Pembrolizumab | Cycle 1 | 60.0 μg/mL | Geometric Coefficient of Variation 22.1 |
| Part A: Favezelimab 70 mg Monotherapy | Cmax of Pembrolizumab | Cycle 4 | 59.3 μg/mL | Geometric Coefficient of Variation 50.1 |
| Part A: Favezelimab 70 mg Monotherapy | Cmax of Pembrolizumab | Cycle 2 | 78.7 μg/mL | Geometric Coefficient of Variation 48.1 |
| Part A: Favezelimab 210 mg Monotherapy | Cmax of Pembrolizumab | Cycle 2 | 69.9 μg/mL | Geometric Coefficient of Variation 37.1 |
| Part A: Favezelimab 210 mg Monotherapy | Cmax of Pembrolizumab | Cycle 1 | 52.8 μg/mL | Geometric Coefficient of Variation 51.5 |
| Part A: Favezelimab 210 mg Monotherapy | Cmax of Pembrolizumab | Cycle 4 | 83.7 μg/mL | Geometric Coefficient of Variation 83 |
| Part A: Favezelimab 700 mg Monotherapy | Cmax of Pembrolizumab | Cycle 1 | 58.7 μg/mL | Geometric Coefficient of Variation 32.3 |
| Part A: Favezelimab 700 mg Monotherapy | Cmax of Pembrolizumab | Cycle 4 | 75.3 μg/mL | Geometric Coefficient of Variation 26.6 |
| Part A: Favezelimab 700 mg Monotherapy | Cmax of Pembrolizumab | Cycle 2 | 66.7 μg/mL | Geometric Coefficient of Variation 29.7 |
| Part A: Favezelimab 700 mg Monotherapy | Cmax of Pembrolizumab | Cycle 3 | 36.7 μg/mL | Geometric Coefficient of Variation 44.2 |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Cmax of Pembrolizumab | Cycle 1 | 74.2 μg/mL | Geometric Coefficient of Variation 39.1 |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Cmax of Pembrolizumab | Cycle 2 | 91.9 μg/mL | Geometric Coefficient of Variation 14.1 |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Cmax of Pembrolizumab | Cycle 4 | 61.2 μg/mL | — |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Cmax of Pembrolizumab | Cycle 2 | 67.6 μg/mL | Geometric Coefficient of Variation 9.36 |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Cmax of Pembrolizumab | Cycle 1 | 57.4 μg/mL | Geometric Coefficient of Variation 32.8 |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Cmax of Pembrolizumab | Cycle 4 | 56.9 μg/mL | Geometric Coefficient of Variation 3.48 |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | Cmax of Pembrolizumab | Cycle 4 | 90.7 μg/mL | Geometric Coefficient of Variation 34.5 |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | Cmax of Pembrolizumab | Cycle 1 | 63.9 μg/mL | Geometric Coefficient of Variation 26.2 |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | Cmax of Pembrolizumab | Cycle 2 | 77.4 μg/mL | Geometric Coefficient of Variation 33.7 |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | Cmax of Pembrolizumab | Cycle 3 | 35.1 μg/mL | Geometric Coefficient of Variation 35.3 |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | Cmax of Pembrolizumab | Cycle 2 | 67.0 μg/mL | Geometric Coefficient of Variation 22.2 |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | Cmax of Pembrolizumab | Cycle 4 | 75.1 μg/mL | Geometric Coefficient of Variation 25.1 |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | Cmax of Pembrolizumab | Cycle 1 | 61.3 μg/mL | Geometric Coefficient of Variation 19.2 |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | Cmax of Pembrolizumab | Cycle 1 | 55.5 μg/mL | Geometric Coefficient of Variation 20.5 |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | Cmax of Pembrolizumab | Cycle 2 | 69.0 μg/mL | Geometric Coefficient of Variation 22.6 |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | Cmax of Pembrolizumab | Cycle 4 | 76.0 μg/mL | Geometric Coefficient of Variation 28.7 |
| Part B: Favezelimab 800 mg Monotherapy (Arm 1) | Cmax of Pembrolizumab | Cycle 1 | 65.0 μg/mL | Geometric Coefficient of Variation 34 |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | Cmax of Pembrolizumab | Cycle 1 | 59.6 μg/mL | Geometric Coefficient of Variation 30.9 |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | Cmax of Pembrolizumab | Cycle 2 | 69.9 μg/mL | Geometric Coefficient of Variation 32.9 |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | Cmax of Pembrolizumab | Cycle 4 | 73.4 μg/mL | Geometric Coefficient of Variation 27.3 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Cmax of Pembrolizumab | Cycle 2 | 61.1 μg/mL | Geometric Coefficient of Variation 55.1 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Cmax of Pembrolizumab | Cycle 1 | 56.6 μg/mL | Geometric Coefficient of Variation 25.6 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Cmax of Pembrolizumab | Cycle 4 | 74.1 μg/mL | Geometric Coefficient of Variation 37.4 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Cmax of Pembrolizumab | Cycle 8 | 93.8 μg/mL | Geometric Coefficient of Variation 25.8 |
Secondary
Maximum Serum Concentration (Cmax) of Favezelimab
Blood for serum samples was collected at pre-specified time points to determine the Cmax of favezelimab. In addition to time points listed in Time Frame, participants enrolled in mainland China also had samples drawn predose on Day 1 of Cycle 5 and postdose on Day 2 of Cycles 4 and 8. Per protocol, different arms had different sampling schedules and therefore were not analyzed for all cycles.
Time frame: Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8
Population: All participants who complied with the protocol sufficiently to ensure that generated data likely exhibiting the effects of treatment, according to the underlying scientific model
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Favezelimab 7 mg Monotherapy | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 2.44 μg/mL | Geometric Coefficient of Variation 46.5 |
| Part A: Favezelimab 7 mg Monotherapy | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 2.39 μg/mL | Geometric Coefficient of Variation 44.4 |
| Part A: Favezelimab 7 mg Monotherapy | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 4 | 3.02 μg/mL | Geometric Coefficient of Variation 6.2 |
| Part A: Favezelimab 21 mg Monotherapy | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 4 | 6.11 μg/mL | Geometric Coefficient of Variation 39.4 |
| Part A: Favezelimab 21 mg Monotherapy | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 8.00 μg/mL | Geometric Coefficient of Variation 22 |
| Part A: Favezelimab 21 mg Monotherapy | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 8.62 μg/mL | Geometric Coefficient of Variation 29.2 |
| Part A: Favezelimab 70 mg Monotherapy | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 21.9 μg/mL | Geometric Coefficient of Variation 34.5 |
| Part A: Favezelimab 70 mg Monotherapy | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 4 | 27.0 μg/mL | Geometric Coefficient of Variation 30.6 |
| Part A: Favezelimab 70 mg Monotherapy | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 19.3 μg/mL | Geometric Coefficient of Variation 47.1 |
| Part A: Favezelimab 210 mg Monotherapy | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 56.8 μg/mL | Geometric Coefficient of Variation 34.9 |
| Part A: Favezelimab 210 mg Monotherapy | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 3 | 19.2 μg/mL | Geometric Coefficient of Variation 138.4 |
| Part A: Favezelimab 210 mg Monotherapy | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 56.7 μg/mL | Geometric Coefficient of Variation 32.2 |
| Part A: Favezelimab 210 mg Monotherapy | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 4 | 58.6 μg/mL | Geometric Coefficient of Variation 34.6 |
| Part A: Favezelimab 700 mg Monotherapy | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 77.4 μg/mL | Geometric Coefficient of Variation 29.9 |
| Part A: Favezelimab 700 mg Monotherapy | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 76.7 μg/mL | Geometric Coefficient of Variation 21.1 |
| Part A: Favezelimab 700 mg Monotherapy | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 4 | 54.0 μg/mL | Geometric Coefficient of Variation 9.3 |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 3 | 150 μg/mL | Geometric Coefficient of Variation 54 |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 247 μg/mL | Geometric Coefficient of Variation 32 |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 224 μg/mL | Geometric Coefficient of Variation 27 |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 4 | 253 μg/mL | Geometric Coefficient of Variation 35 |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 3 | 272 μg/mL | Geometric Coefficient of Variation 45.6 |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 4 | 265 μg/mL | Geometric Coefficient of Variation 32.2 |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 8 | 292 μg/mL | Geometric Coefficient of Variation 26.6 |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 247 μg/mL | Geometric Coefficient of Variation 36.6 |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 248 μg/mL | Geometric Coefficient of Variation 27.8 |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 2.67 μg/mL | Geometric Coefficient of Variation 97.4 |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 3.16 μg/mL | Geometric Coefficient of Variation 44.9 |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 9.65 μg/mL | Geometric Coefficient of Variation 19.6 |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 8.62 μg/mL | Geometric Coefficient of Variation 17.6 |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 4 | 24.5 μg/mL | — |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 23.7 μg/mL | Geometric Coefficient of Variation 21.9 |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 20.8 μg/mL | Geometric Coefficient of Variation 21.8 |
| Part B: Favezelimab 800 mg Monotherapy (Arm 1) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 74.9 μg/mL | Geometric Coefficient of Variation 28.8 |
| Part B: Favezelimab 800 mg Monotherapy (Arm 1) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 70.6 μg/mL | Geometric Coefficient of Variation 23.3 |
| Part B: Favezelimab 800 mg Monotherapy (Arm 1) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 4 | 55.3 μg/mL | Geometric Coefficient of Variation 11.8 |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 222 μg/mL | Geometric Coefficient of Variation 15.8 |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 216 μg/mL | Geometric Coefficient of Variation 19.9 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 301 μg/mL | Geometric Coefficient of Variation 18 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 271 μg/mL | Geometric Coefficient of Variation 20.7 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 3 | 272 μg/mL | Geometric Coefficient of Variation 45.6 |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 4 | 332 μg/mL | Geometric Coefficient of Variation 19.4 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 1.80 μg/mL | Geometric Coefficient of Variation 17.9 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 2.30 μg/mL | Geometric Coefficient of Variation 21.4 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 4 | 3.02 μg/mL | Geometric Coefficient of Variation 6.3 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 6.88 μg/mL | Geometric Coefficient of Variation 25.2 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 4 | 6.11 μg/mL | Geometric Coefficient of Variation 39.4 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 6.88 μg/mL | Geometric Coefficient of Variation 35.3 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 17.9 μg/mL | Geometric Coefficient of Variation 74 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 20.2 μg/mL | Geometric Coefficient of Variation 48.9 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 4 | 28.3 μg/mL | Geometric Coefficient of Variation 42.5 |
| Part B: MK-4280A (Arm 5) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 4 | 58.6 μg/mL | Geometric Coefficient of Variation 34.6 |
| Part B: MK-4280A (Arm 5) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 56.7 μg/mL | Geometric Coefficient of Variation 32.2 |
| Part B: MK-4280A (Arm 5) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 56.8 μg/mL | Geometric Coefficient of Variation 34.9 |
| Part B: MK-4280A (Arm 5) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 3 | 19.2 μg/mL | Geometric Coefficient of Variation 138.4 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 83.3 μg/mL | Geometric Coefficient of Variation 19.2 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 4 | 51.4 μg/mL | — |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 80.0 μg/mL | Geometric Coefficient of Variation 37.5 |
| Part B: Favezelimab Switch Over to Favezelimab 800 mg + Pembrolizumab 200 mg (Switch Over to Arm 2C) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 4 | 145 μg/mL | Geometric Coefficient of Variation 37.5 |
| Part B: Favezelimab Switch Over to Favezelimab 800 mg + Pembrolizumab 200 mg (Switch Over to Arm 2C) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 238 μg/mL | Geometric Coefficient of Variation 58.9 |
| Part B: Favezelimab Switch Over to Favezelimab 800 mg + Pembrolizumab 200 mg (Switch Over to Arm 2C) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 252 μg/mL | Geometric Coefficient of Variation 46.6 |
| Part B: Second Course Favezelimab 200 mg + Pembrolizumab 200 mg (Second Course Arm 2A) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 3 | 150 μg/mL | Geometric Coefficient of Variation 54 |
| Part B: Second Course Favezelimab 200 mg + Pembrolizumab 200 mg (Second Course Arm 2A) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 250 μg/mL | Geometric Coefficient of Variation 31.5 |
| Part B: Second Course Favezelimab 200 mg + Pembrolizumab 200 mg (Second Course Arm 2A) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 4 | 269 μg/mL | Geometric Coefficient of Variation 29.4 |
| Part B: Second Course Favezelimab 200 mg + Pembrolizumab 200 mg (Second Course Arm 2A) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 223 μg/mL | Geometric Coefficient of Variation 26.5 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 4 | 252 μg/mL | Geometric Coefficient of Variation 26.1 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 228 μg/mL | Geometric Coefficient of Variation 53.8 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 248 μg/mL | Geometric Coefficient of Variation 20.5 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 219 μg/mL | Geometric Coefficient of Variation 23.6 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 245 μg/mL | Geometric Coefficient of Variation 25.5 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 4 | 267 μg/mL | Geometric Coefficient of Variation 35.7 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 281 μg/mL | Geometric Coefficient of Variation 35.7 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 266 μg/mL | Geometric Coefficient of Variation 35.4 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 244 μg/mL | Geometric Coefficient of Variation 33.9 |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 4 | 262 μg/mL | Geometric Coefficient of Variation 34.5 |
| Part B: MK-4280A (Arm 5) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 2 | 240 μg/mL | Geometric Coefficient of Variation 28.6 |
| Part B: MK-4280A (Arm 5) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 4 | 254 μg/mL | Geometric Coefficient of Variation 35.9 |
| Part B: MK-4280A (Arm 5) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 8 | 292 μg/mL | Geometric Coefficient of Variation 26.6 |
| Part B: MK-4280A (Arm 5) | Maximum Serum Concentration (Cmax) of Favezelimab | Cycle 1 | 234 μg/mL | Geometric Coefficient of Variation 24.5 |
Secondary
Objective Response Rate (ORR) for Part B Participants
ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experienced a CR or PR is presented.
Time frame: Up to approximately 92 months
Population: All participants enrolled in Part B with a baseline scan with measurable disease by investigator assessment, who received ≥1 dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Favezelimab 7 mg Monotherapy | Objective Response Rate (ORR) for Part B Participants | 0.0 Percentage of Participants |
| Part A: Favezelimab 21 mg Monotherapy | Objective Response Rate (ORR) for Part B Participants | 3.8 Percentage of Participants |
| Part A: Favezelimab 70 mg Monotherapy | Objective Response Rate (ORR) for Part B Participants | 15.0 Percentage of Participants |
| Part A: Favezelimab 210 mg Monotherapy | Objective Response Rate (ORR) for Part B Participants | 7.5 Percentage of Participants |
| Part A: Favezelimab 700 mg Monotherapy | Objective Response Rate (ORR) for Part B Participants | 15.0 Percentage of Participants |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Objective Response Rate (ORR) for Part B Participants | 7.3 Percentage of Participants |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Objective Response Rate (ORR) for Part B Participants | 5.1 Percentage of Participants |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | Objective Response Rate (ORR) for Part B Participants | 10.5 Percentage of Participants |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | Objective Response Rate (ORR) for Part B Participants | 25.0 Percentage of Participants |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | Objective Response Rate (ORR) for Part B Participants | 0.0 Percentage of Participants |
| Part B: Favezelimab 800 mg Monotherapy (Arm 1) | Objective Response Rate (ORR) for Part B Participants | 7.5 Percentage of Participants |
95% CI: [-7.3, 22.9]
Secondary
Predose Serum Concentration of Favezelimab
Blood for serum samples was collected at pre-specified time points to determine the predose serum concentration of favezelimab, which is presented.
Time frame: Predose on Day 1 of cycles 1-4, 6, and 8. Per protocol, different arms had different sampling schedules and therefore were not analyzed for all cycles.
Population: All participants who complied with the protocol sufficiently to ensure that generated data likely exhibiting the effects of treatment, according to the underlying scientific model
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: Favezelimab 7 mg Monotherapy | Predose Serum Concentration of Favezelimab | Cycle 3 | 0.00 μg/mL |
| Part A: Favezelimab 7 mg Monotherapy | Predose Serum Concentration of Favezelimab | Cycle 1 | 0.00 μg/mL |
| Part A: Favezelimab 7 mg Monotherapy | Predose Serum Concentration of Favezelimab | Cycle 2 | 0.00 μg/mL |
| Part A: Favezelimab 21 mg Monotherapy | Predose Serum Concentration of Favezelimab | Cycle 4 | 0.00 μg/mL |
| Part A: Favezelimab 21 mg Monotherapy | Predose Serum Concentration of Favezelimab | Cycle 8 | 0.00 μg/mL |
| Part A: Favezelimab 21 mg Monotherapy | Predose Serum Concentration of Favezelimab | Cycle 1 | 0.00 μg/mL |
| Part A: Favezelimab 21 mg Monotherapy | Predose Serum Concentration of Favezelimab | Cycle 2 | 0.00 μg/mL |
| Part A: Favezelimab 21 mg Monotherapy | Predose Serum Concentration of Favezelimab | Cycle 3 | 0.00 μg/mL |
| Part A: Favezelimab 70 mg Monotherapy | Predose Serum Concentration of Favezelimab | Cycle 2 | 0.0361 μg/mL |
| Part A: Favezelimab 70 mg Monotherapy | Predose Serum Concentration of Favezelimab | Cycle 3 | 0.00 μg/mL |
| Part A: Favezelimab 70 mg Monotherapy | Predose Serum Concentration of Favezelimab | Cycle 1 | 0.00 μg/mL |
| Part A: Favezelimab 210 mg Monotherapy | Predose Serum Concentration of Favezelimab | Cycle 4 | 0.00 μg/mL |
| Part A: Favezelimab 210 mg Monotherapy | Predose Serum Concentration of Favezelimab | Cycle 2 | 0.00 μg/mL |
| Part A: Favezelimab 210 mg Monotherapy | Predose Serum Concentration of Favezelimab | Cycle 3 | 0.00 μg/mL |
| Part A: Favezelimab 210 mg Monotherapy | Predose Serum Concentration of Favezelimab | Cycle 6 | 0.00 μg/mL |
| Part A: Favezelimab 210 mg Monotherapy | Predose Serum Concentration of Favezelimab | Cycle 8 | 0.00 μg/mL |
| Part A: Favezelimab 210 mg Monotherapy | Predose Serum Concentration of Favezelimab | Cycle 1 | 0.00 μg/mL |
| Part A: Favezelimab 700 mg Monotherapy | Predose Serum Concentration of Favezelimab | Cycle 4 | 0.00 μg/mL |
| Part A: Favezelimab 700 mg Monotherapy | Predose Serum Concentration of Favezelimab | Cycle 1 | 0.00 μg/mL |
| Part A: Favezelimab 700 mg Monotherapy | Predose Serum Concentration of Favezelimab | Cycle 6 | 15.1 μg/mL |
| Part A: Favezelimab 700 mg Monotherapy | Predose Serum Concentration of Favezelimab | Cycle 3 | 0.00 μg/mL |
| Part A: Favezelimab 700 mg Monotherapy | Predose Serum Concentration of Favezelimab | Cycle 2 | 0.00 μg/mL |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 4 | 1.09 μg/mL |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 1 | 0.00 μg/mL |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 6 | 1.58 μg/mL |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 8 | 1.09 μg/mL |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 2 | 0.00 μg/mL |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 3 | 0.00 μg/mL |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 1 | 0.00 μg/mL |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 2 | 1.52 μg/mL |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 3 | 1.95 μg/mL |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 4 | 2.26 μg/mL |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 6 | 3.63 μg/mL |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 8 | 4.18 μg/mL |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 4 | 0.429 μg/mL |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 8 | 0.00 μg/mL |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 2 | 1.26 μg/mL |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 6 | 50.6 μg/mL |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 1 | 0.00 μg/mL |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 3 | 0.225 μg/mL |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 1 | 0.00 μg/mL |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 4 | 4.54 μg/mL |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 3 | 4.48 μg/mL |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 2 | 3.28 μg/mL |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 3 | 28.2 μg/mL |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 1 | 0.00 μg/mL |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | Predose Serum Concentration of Favezelimab | Cycle 2 | 12.9 μg/mL |
| Part B: Favezelimab 800 mg Monotherapy (Arm 1) | Predose Serum Concentration of Favezelimab | Cycle 4 | 31.0 μg/mL |
| Part B: Favezelimab 800 mg Monotherapy (Arm 1) | Predose Serum Concentration of Favezelimab | Cycle 3 | 34.7 μg/mL |
| Part B: Favezelimab 800 mg Monotherapy (Arm 1) | Predose Serum Concentration of Favezelimab | Cycle 1 | 0.00 μg/mL |
| Part B: Favezelimab 800 mg Monotherapy (Arm 1) | Predose Serum Concentration of Favezelimab | Cycle 2 | 23.6 μg/mL |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | Predose Serum Concentration of Favezelimab | Cycle 3 | 23.7 μg/mL |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | Predose Serum Concentration of Favezelimab | Cycle 2 | 15.0 μg/mL |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | Predose Serum Concentration of Favezelimab | Cycle 8 | 18.4 μg/mL |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | Predose Serum Concentration of Favezelimab | Cycle 4 | 25.0 μg/mL |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | Predose Serum Concentration of Favezelimab | Cycle 6 | 26.9 μg/mL |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | Predose Serum Concentration of Favezelimab | Cycle 1 | 0.00 μg/mL |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Predose Serum Concentration of Favezelimab | Cycle 6 | 35.1 μg/mL |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Predose Serum Concentration of Favezelimab | Cycle 2 | 21.8 μg/mL |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Predose Serum Concentration of Favezelimab | Cycle 3 | 37.1 μg/mL |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Predose Serum Concentration of Favezelimab | Cycle 1 | 0.00 μg/mL |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Predose Serum Concentration of Favezelimab | Cycle 8 | 30.8 μg/mL |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Predose Serum Concentration of Favezelimab | Cycle 4 | 42.0 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Predose Serum Concentration of Favezelimab | Cycle 1 | 0.00 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Predose Serum Concentration of Favezelimab | Cycle 3 | 14.8 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Predose Serum Concentration of Favezelimab | Cycle 4 | 20.5 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Predose Serum Concentration of Favezelimab | Cycle 6 | 18.6 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Predose Serum Concentration of Favezelimab | Cycle 8 | 20.7 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Predose Serum Concentration of Favezelimab | Cycle 2 | 13.3 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Predose Serum Concentration of Favezelimab | Cycle 4 | 45.6 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Predose Serum Concentration of Favezelimab | Cycle 8 | 51.1 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Predose Serum Concentration of Favezelimab | Cycle 6 | 40.3 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Predose Serum Concentration of Favezelimab | Cycle 2 | 25.2 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Predose Serum Concentration of Favezelimab | Cycle 3 | 39.5 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Predose Serum Concentration of Favezelimab | Cycle 1 | 0.00 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Predose Serum Concentration of Favezelimab | Cycle 8 | 49.2 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Predose Serum Concentration of Favezelimab | Cycle 1 | 0.00 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Predose Serum Concentration of Favezelimab | Cycle 4 | 38.4 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Predose Serum Concentration of Favezelimab | Cycle 3 | 35.8 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Predose Serum Concentration of Favezelimab | Cycle 6 | 38.1 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Predose Serum Concentration of Favezelimab | Cycle 2 | 20.1 μg/mL |
| Part B: MK-4280A (Arm 5) | Predose Serum Concentration of Favezelimab | Cycle 2 | 27.0 μg/mL |
| Part B: MK-4280A (Arm 5) | Predose Serum Concentration of Favezelimab | Cycle 1 | 0.00 μg/mL |
| Part B: MK-4280A (Arm 5) | Predose Serum Concentration of Favezelimab | Cycle 3 | 43.3 μg/mL |
| Part B: MK-4280A (Arm 5) | Predose Serum Concentration of Favezelimab | Cycle 8 | 64.3 μg/mL |
| Part B: MK-4280A (Arm 5) | Predose Serum Concentration of Favezelimab | Cycle 4 | 51.2 μg/mL |
| Part B: MK-4280A (Arm 5) | Predose Serum Concentration of Favezelimab | Cycle 6 | 59.6 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) | Predose Serum Concentration of Favezelimab | Cycle 6 | 27.3 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) | Predose Serum Concentration of Favezelimab | Cycle 8 | 23.9 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) | Predose Serum Concentration of Favezelimab | Cycle 4 | 16.8 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) | Predose Serum Concentration of Favezelimab | Cycle 1 | 0.00 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) | Predose Serum Concentration of Favezelimab | Cycle 3 | 19.1 μg/mL |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) | Predose Serum Concentration of Favezelimab | Cycle 2 | 12.4 μg/mL |