Study of Favezelimab (MK-4280) as Monotherapy and in Combination With Pembrolizumab (MK-3475) With or Without Chemotherapy or Lenvatinib (MK-7902) AND Favezelimab/Pembrolizumab (MK-4280A) as Monotherapy in Adults With Advanced Solid Tumors (MK-4280-001)

NCT02720068 | Completed Phase 1 Results FDA Drug

• 4 other identifiers: 4280-001MK-4280-0011839712017-001464-38
• Study Type: interventional
• Target: 481
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Neoplasms

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)

Outcome Measures

Primary Outcomes (3)

• 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.

  Up to 21 days (Cycle 1)

• 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.

  Up to approximately 31.3 months

• 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.

  Up to approximately 28.3 months

Secondary Outcomes (11)

• Objective Response Rate (ORR) for Part B Participants

  Up to approximately 92 months

• 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

• 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

• 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

• 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

Study Arms (18)

Part A: Favezelimab 7 mg Monotherapy

EXPERIMENTAL

Participants received favezelimab 7 mg intravenous (IV) infusion on Day 1 of each 21-day cycle.

Biological: Favezelimab

Part A: Favezelimab 21 mg Monotherapy

EXPERIMENTAL

Participants received favezelimab 21 mg IV infusion on Day 1 of each 21-day cycle.

Biological: Favezelimab

Part A: Favezelimab 70 mg Monotherapy

EXPERIMENTAL

Participants received favezelimab 70 mg IV infusion on Day 1 of each 21-day cycle.

Biological: Favezelimab

Part A: Favezelimab 210 mg Monotherapy

EXPERIMENTAL

Participants received favezelimab 210 mg IV infusion on Day 1 of each 21-day cycle.

Biological: Favezelimab

Part A: Favezelimab 700 mg Monotherapy

EXPERIMENTAL

Participants received favezelimab 700 mg IV infusion on Day 1 of each 21-day cycle.

Biological: Favezelimab

Part A: Favezelimab 7 mg + Pembrolizumab 200 mg

EXPERIMENTAL

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.

Biological: Favezelimab; Biological: Pembrolizumab

Part A: Favezelimab 21 mg + Pembrolizumab 200 mg

EXPERIMENTAL

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.

Biological: Favezelimab; Biological: Pembrolizumab

Part A: Favezelimab 70 mg + Pembrolizumab 200 mg

EXPERIMENTAL

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.

Biological: Favezelimab; Biological: Pembrolizumab

Part A: Favezelimab 210 mg + Pembrolizumab 200 mg

EXPERIMENTAL

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.

Biological: Favezelimab; Biological: Pembrolizumab

Part A: Favezelimab 700 mg + Pembrolizumab 200 mg

EXPERIMENTAL

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.

Biological: Favezelimab; Biological: Pembrolizumab

Part B: Favezelimab 800 mg Monotherapy (Arm 1)

EXPERIMENTAL

Participants received favezelimab 800 mg monotherapy IV infusion on Day 1 of each 21-day cycle.

Biological: Favezelimab

Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A)

EXPERIMENTAL

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.

Biological: Favezelimab; Biological: Pembrolizumab

Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B)

EXPERIMENTAL

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.

Biological: Favezelimab; Biological: Pembrolizumab

Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C)

EXPERIMENTAL

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.

Biological: Favezelimab; Biological: Pembrolizumab

Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3)

EXPERIMENTAL

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 \[Q2W\]).

Biological: Favezelimab; Biological: Pembrolizumab; Drug: Oxaliplatin; Drug: Leucovorin (Calcium Folinate); Drug: Fluorouracil [5-FU]

Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4)

EXPERIMENTAL

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).

Biological: Favezelimab; Biological: Pembrolizumab; Drug: Irinotecan; Drug: Leucovorin (Calcium Folinate); Drug: Fluorouracil [5-FU]

Part B: MK-4280A (Arm 5)

EXPERIMENTAL

Participants received MK-4280A, a coformulation of favezelimab 800 mg + pembrolizumab 200 mg IV infusion on Day 1 of each 21-day cycle.

Biological: Favezelimab/Pembrolizumab

Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6)

EXPERIMENTAL

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.

Biological: Favezelimab; Biological: Pembrolizumab; Drug: Lenvatinib

Interventions

Favezelimab BIOLOGICAL

IV infusion

Also known as: MK-4280

Part A: Favezelimab 21 mg + Pembrolizumab 200 mg; Part A: Favezelimab 21 mg Monotherapy; Part A: Favezelimab 210 mg + Pembrolizumab 200 mg; Part A: Favezelimab 210 mg Monotherapy; Part A: Favezelimab 7 mg + Pembrolizumab 200 mg; Part A: Favezelimab 7 mg Monotherapy; Part A: Favezelimab 70 mg + Pembrolizumab 200 mg; Part A: Favezelimab 70 mg Monotherapy; Part A: Favezelimab 700 mg + Pembrolizumab 200 mg; Part A: Favezelimab 700 mg Monotherapy; 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: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4); Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6); Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3); Part B: Favezelimab 800 mg Monotherapy (Arm 1)

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-3475, KEYTRUDA®

Part A: Favezelimab 21 mg + Pembrolizumab 200 mg; Part A: Favezelimab 210 mg + Pembrolizumab 200 mg; Part A: Favezelimab 7 mg + Pembrolizumab 200 mg; Part A: Favezelimab 70 mg + Pembrolizumab 200 mg; Part A: Favezelimab 700 mg + Pembrolizumab 200 mg; 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: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4); Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6); Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3)

Oxaliplatin DRUG

IV infusion

Also known as: ELOXATIN®

Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3)

Irinotecan DRUG

IV infusion

Also known as: CAMPTOSAR®

Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4)

Leucovorin (Calcium Folinate) DRUG

IV infusion

Also known as: WELLCOVORIN®

Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4); Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3)

Fluorouracil [5-FU] DRUG

IV infusion

Also known as: ADRUCIL®

Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4); Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3)

Favezelimab/Pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-4280A

Part B: MK-4280A (Arm 5)

Lenvatinib DRUG

Oral

Also known as: E7080, MK-7902, LENVIMA®

Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (2)

• Study of Favezelimab (MK-4280) as Monotherapy and in Combination With Pembrolizumab (MK-3475) With or Without Chemotherapy or Lenvatinib (MK-7902) AND Favezelimab/Pembrolizumab (MK-4280A) as Monotherapy in Adults With Advanced Solid Tumors (MK-4280-001) - Full Text View - ClinicalTrials.gov

  BACKGROUND

• Garralda E, Sukari A, Lakhani NJ, Patnaik A, Lou Y, Im SA, Golan T, Geva R, Wermke M, de Miguel M, Palcza J, Jha S, Chaney M, Abraham AK, Healy J, Falchook GS. A first-in-human study of the anti-LAG-3 antibody favezelimab plus pembrolizumab in previously treated, advanced microsatellite stable colorectal cancer. ESMO Open. 2022 Dec;7(6):100639. doi: 10.1016/j.esmoop.2022.100639. Epub 2022 Dec 6.

  PMID: 36493599 RESULT

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; Oxaliplatin; Irinotecan; Leucovorin; Fluorouracil; lenvatinib

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 22, 2016
• First Posted: March 25, 2016
• Study Start: May 2, 2016
• Primary Completion: March 15, 2024
• Study Completion: March 15, 2024
• Last Updated: May 30, 2025
• Results First Posted: May 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share