Study to Evaluate the Safety and Efficacy of a Combination of Favezelimab (MK-4280) and Pembrolizumab (MK-3475) in Participants With Hematologic Malignancies (MK-4280-003)

NCT03598608 | Completed Phase 1 FDA Drug

• 5 other identifiers: 4280-003MK-4280-0032023-503587-17-00U1111-1287-54052018-001461-16
• Study Type: interventional
• Target: 137
• Locations: 6 countries
• Sites: 25

Brief Summary

This study will evaluate the safety and efficacy of favezelimab (MK-4280) in combination with pembrolizumab (MK-3475) using a non-randomized study design in participants with the following hematological malignancies:

• classical Hodgkin lymphoma (cHL)
• diffuse large B-cell lymphoma (DLBCL)
• indolent non-Hodgkin lymphoma (iNHL) This study will also evaluate the safety and efficacy of pembrolizumab or favezelimab administered as monotherapy in participants with cHL using a 1:1 randomized study design. The study will have 2 phases: a safety lead-in and an efficacy expansion phase. The recommended Phase 2 dose (RP2D) will be determined in the safety lead-in phase by evaluating dose-limiting toxicities. There is no primary hypothesis for this study.

Conditions

Hodgkin Disease; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell

Keywords

programmed cell death 1 (PD-1, PD1); programmed cell death ligand 1 (PD-L1, PDL1); programmed cell death ligand 2 (PD-L2, PDL2)

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants Experiencing a Dose-limiting Toxicity (DLT)

  DLT will be defined as any drug-related adverse event (AE) observed during the DLT evaluation period (Cycle 1) that results in a change to a given dose or a delay in initiating the next cycle and reported as the percentage of participants experiencing a DLT defined by the National Cancer Institute Common Terminology for Adverse Events version 4.0.

  Cycle 1 (up to 21 days)

• Percentage of Participants Experiencing an Adverse Event (AE)

  Percentage of participants experiencing an AE defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study treatment

  From time of signing informed consent form (ICF) until the end of follow-up (up to approximately 27 months)

• Percentage of Participants with Treatment Discontinuations Due to an AE

  Percentage of participants discontinuing study treatment due to an AE

  From time of signing informed consent form (ICF) until the end of study treatment (up to approximately 24 months)

Secondary Outcomes (1)

• Objective Response Rate (ORR)

  Up to approximately 24 months

Study Arms (7)

Part A: Favezelimab Dose A+pembrolizumab

EXPERIMENTAL

Participants receive 200 mg pembrolizumab by intravenous (IV) infusion followed by favezelimab Dose A by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).

Biological: pembrolizumab; Biological: Favezelimab

Part A: Favezelimab Dose B+pembrolizumab

EXPERIMENTAL

Participants receive 200 mg pembrolizumab by IV infusion followed by favezelimab Dose B by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).

Biological: pembrolizumab; Biological: Favezelimab

Part A: Favezelimab Dose C+Pembrolizumab

EXPERIMENTAL

Participants receive 200 mg pembrolizumab by IV infusion followed by favezelimab Dose C by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).

Biological: pembrolizumab; Biological: Favezelimab

Part B: cHL-Combination Therapy

EXPERIMENTAL

Participants with cHL receive 200 mg pembrolizumab by IV infusion followed by the recommended Phase 2 dose (RP2D) of favezelimab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).

Biological: pembrolizumab; Biological: Favezelimab

Part B: DLBCL-Combination Therapy

EXPERIMENTAL

Participants with DLBCL receive 200 mg pembrolizumab by IV infusion followed by the RP2D of favezelimab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).

Biological: pembrolizumab; Biological: Favezelimab

Part B: iNHL-Combination Therapy

EXPERIMENTAL

Participants with iNHL receive 200 mg pembrolizumab by IV infusion followed by the RP2D of favezelimab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).

Biological: pembrolizumab; Biological: Favezelimab

Part B: Randomized cHL-Monotherapy

EXPERIMENTAL

Participants with cHL receive either pembrolizumab by IV infusion or the RP2D of favezelimab by IV infusion on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to approximately 2 years).

Biological: pembrolizumab; Biological: Favezelimab

Interventions

pembrolizumab BIOLOGICAL

Administered as an IV infusion every 3 weeks (Q3W)

Also known as: KEYTRUDA®, MK-3475

Part A: Favezelimab Dose A+pembrolizumab; Part A: Favezelimab Dose B+pembrolizumab; Part A: Favezelimab Dose C+Pembrolizumab; Part B: DLBCL-Combination Therapy; Part B: Randomized cHL-Monotherapy; Part B: cHL-Combination Therapy; Part B: iNHL-Combination Therapy

Favezelimab BIOLOGICAL

Administered as an IV infusion Q3W

Also known as: MK-4280

Part A: Favezelimab Dose A+pembrolizumab; Part A: Favezelimab Dose B+pembrolizumab; Part A: Favezelimab Dose C+Pembrolizumab; Part B: DLBCL-Combination Therapy; Part B: Randomized cHL-Monotherapy; Part B: cHL-Combination Therapy; Part B: iNHL-Combination Therapy

Eligibility Criteria

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

You may qualify if:

• Has measurable disease, defined as ≥1 lesion that can be accurately measured in 2 dimensions with diagnostic quality cross sectional anatomic imaging (computed tomography or magnetic resonance imaging). Minimum measurement must be \>15 mm in the longest diameter or \>10 mm in the short axis
• Is able to provide a core or excisional tumor biopsy for biomarker analysis from an archival (within 3 months) or newly obtained biopsy at screening
• Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)

You may not qualify if:

• Has known clinically active central nervous system (CNS) involvement
• Has received prior therapy with an anti-lymphocyte activation gene-3 (LAG-3) antibody
• Has received chimeric antigen receptors (CAR)-T-cell therapy for cHL and DLBCL Cohorts
• Has received prior anticancer therapy or thoracic radiation therapy within 14 days before the first dose of study treatment
• Has ≥Grade 2 non-hematological residual toxicities from prior therapy
• Has had a prior anticancer monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤Grade 1 or at baseline) from AEs due to agents administered ≥4 weeks earlier
• Has received a live vaccine within 30 days prior to first dose of study treatment. Administration of killed vaccines are allowed
• Has received an investigational agent or used an investigational device within 4 weeks prior to intervention administration
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
• Has a known additional malignancy that is progressing or requires active treatment with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
• Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Has an active infection requiring intravenous systemic therapy
• Has a known history of human immunodeficiency virus (HIV) infection
• Has known, active hepatitis B or hepatitis C infection

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (25)

Banner MD Anderson Cancer Center ( Site 0020)

Gilbert, Arizona, 85234, United States

Location

City of Hope ( Site 0001)

Duarte, California, 91010, United States

Location

Ronald Reagan UCLA Medical Center (Radiological Sciences) ( Site 0007)

Los Angeles, California, 90095, United States

Location

Pacific Cancer Care ( Site 0006)

Monterey, California, 93940, United States

Location

University of California San Francisco ( Site 0023)

San Francisco, California, 94143, United States

Location

Dana Farber Cancer Institute ( Site 0002)

Boston, Massachusetts, 02215, United States

Location

Fox Chase Cancer Center ( Site 0019)

Philadelphia, Pennsylvania, 19111, United States

Location

Texas Oncology-Austin Midtown ( Site 8002)

Austin, Texas, 78705, United States

Location

Concord Repatriation & General Hospital ( Site 0203)

Concord, New South Wales, 2139, Australia

Location

Princess Alexandra Hospital ( Site 0204)

Woollongabba, Queensland, 4102, Australia

Location

Monash Health ( Site 0201)

Clayton, Victoria, 3168, Australia

Location

St Vincent s Hospital (Melbourne) Limited ( Site 0202)

Fitzroy, Victoria, 3065, Australia

Location

BC Cancer ( Site 0107)

Vancouver, British Columbia, V5Z 1L3, Canada

Location

CancerCare Manitoba ( Site 0101)

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Princess Margaret Cancer Centre ( Site 0100)

Toronto, Ontario, M5G 2M9, Canada

Location

Jewish General Hospital ( Site 0105)

Montreal, Quebec, H3T 1E2, Canada

Location

U. klinikum Koeln AOER ( Site 0326)

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Universitaetsklinikum Leipzig AOeR ( Site 0327)

Leipzig, Saxony, 4103, Germany

Location

Rambam Medical Center ( Site 0382)

Haifa, 3109601, Israel

Location

Hadassah Ein Karem Jerusalem ( Site 0383)

Jerusalem, 9112001, Israel

Location

Chaim Sheba Medical Center. ( Site 0380)

Ramat Gan, 5262001, Israel

Location

Sourasky Medical Center ( Site 0381)

Tel Aviv, 6423906, Israel

Location

A.O. Universitaria Policlinico S. Orsola-Malpighi ( Site 0351)

Bologna, Emilia-Romagna, 40138, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori ( Site 0354)

Meldola, Forli-Cesena, 47014, Italy

Location

Humanitas-U.O di Oncologia medica ed Ematologia ( Site 0352)

Rozzano, Milano, 20089, Italy

Location

Related Publications (1)

• Armand P, Zinzani PL, Timmerman J, Johnson NA, Lavie D, Thiagarajan K, Topp BG, Pillai P, Herrera AF. Estimating efficacy of favezelimab plus pembrolizumab relative to pembrolizumab in anti-PD-1-refractory Hodgkin lymphoma. Blood Adv. 2025 Oct 14;9(19):4987-4995. doi: 10.1182/bloodadvances.2024014654.

  PMID: 40668662 DERIVED

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Participants in Part B: Randomized cHL-Monotherapy arm in the study will be randomized (1:1 ratio) to receive pembrolizumab or favezelimab.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2018
• First Posted: July 26, 2018
• Study Start: October 17, 2018
• Primary Completion: January 28, 2026
• Study Completion: January 28, 2026
• Last Updated: February 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

IL (4); DE (2); AU (4); CA (4); US (8); IT (3)