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)

NCT ID: NCT03598608

Last Updated: 2026-01-20

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 174 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-17
• Study Completion Date: 2026-01-28

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.

Detailed Description

Per protocol amendment 7, the secondary serum concentration endpoints were removed and will not be reported.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A: Favezelimab Dose A+pembrolizumab

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).

Group Type: EXPERIMENTAL

pembrolizumab

Intervention Type: BIOLOGICAL

Administered as an IV infusion every 3 weeks (Q3W)

Favezelimab

Intervention Type: BIOLOGICAL

Administered as an IV infusion Q3W

Part A: Favezelimab Dose B+pembrolizumab

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).

Group Type: EXPERIMENTAL

pembrolizumab

Intervention Type: BIOLOGICAL

Administered as an IV infusion every 3 weeks (Q3W)

Favezelimab

Intervention Type: BIOLOGICAL

Administered as an IV infusion Q3W

Part A: Favezelimab Dose C+Pembrolizumab

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).

Group Type: EXPERIMENTAL

pembrolizumab

Intervention Type: BIOLOGICAL

Administered as an IV infusion every 3 weeks (Q3W)

Favezelimab

Intervention Type: BIOLOGICAL

Administered as an IV infusion Q3W

Part B: cHL-Combination Therapy

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).

Group Type: EXPERIMENTAL

pembrolizumab

Intervention Type: BIOLOGICAL

Administered as an IV infusion every 3 weeks (Q3W)

Favezelimab

Intervention Type: BIOLOGICAL

Administered as an IV infusion Q3W

Part B: DLBCL-Combination Therapy

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).

Group Type: EXPERIMENTAL

pembrolizumab

Intervention Type: BIOLOGICAL

Administered as an IV infusion every 3 weeks (Q3W)

Favezelimab

Intervention Type: BIOLOGICAL

Administered as an IV infusion Q3W

Part B: iNHL-Combination Therapy

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).

Group Type: EXPERIMENTAL

pembrolizumab

Intervention Type: BIOLOGICAL

Administered as an IV infusion every 3 weeks (Q3W)

Favezelimab

Intervention Type: BIOLOGICAL

Administered as an IV infusion Q3W

Part B: Randomized cHL-Monotherapy

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).

Group Type: EXPERIMENTAL

pembrolizumab

Intervention Type: BIOLOGICAL

Administered as an IV infusion every 3 weeks (Q3W)

Favezelimab

Intervention Type: BIOLOGICAL

Administered as an IV infusion Q3W

Interventions

pembrolizumab

Administered as an IV infusion every 3 weeks (Q3W)

Intervention Type: BIOLOGICAL

Favezelimab

Administered as an IV infusion Q3W

Intervention Type: BIOLOGICAL

Other Intervention Names

KEYTRUDA®; MK-3475; MK-4280

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• 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
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
• Has had an allogeneic hematopoetic stem cell/solid organ transplantation within the last 5 years

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Banner MD Anderson Cancer Center ( Site 0020)

Gilbert, Arizona, United States

City of Hope ( Site 0001)

Duarte, California, United States

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

Los Angeles, California, United States

Pacific Cancer Care ( Site 0006)

Monterey, California, United States

University of California San Francisco ( Site 0023)

San Francisco, California, United States

Dana Farber Cancer Institute ( Site 0002)

Boston, Massachusetts, United States

Fox Chase Cancer Center ( Site 0019)

Philadelphia, Pennsylvania, United States

Texas Oncology-Austin Midtown ( Site 8002)

Austin, Texas, United States

Concord Repatriation & General Hospital ( Site 0203)

Concord, New South Wales, Australia

Princess Alexandra Hospital ( Site 0204)

Woollongabba, Queensland, Australia

Monash Health ( Site 0201)

Clayton, Victoria, Australia

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

Fitzroy, Victoria, Australia

BC Cancer ( Site 0107)

Vancouver, British Columbia, Canada

CancerCare Manitoba ( Site 0101)

Winnipeg, Manitoba, Canada

Princess Margaret Cancer Centre ( Site 0100)

Toronto, Ontario, Canada

Jewish General Hospital ( Site 0105)

Montreal, Quebec, Canada

U. klinikum Koeln AOER ( Site 0326)

Cologne, North Rhine-Westphalia, Germany

Universitaetsklinikum Leipzig AOeR ( Site 0327)

Leipzig, Saxony, Germany

Rambam Medical Center ( Site 0382)

Haifa, , Israel

Hadassah Ein Karem Jerusalem ( Site 0383)

Jerusalem, , Israel

Chaim Sheba Medical Center. ( Site 0380)

Ramat Gan, , Israel

Sourasky Medical Center ( Site 0381)

Tel Aviv, , Israel

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

Bologna, Emilia-Romagna, Italy

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

Meldola, Forli-Cesena, Italy

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

Rozzano, Milano, Italy

Countries

United States; Australia; Canada; Germany; Israel; Italy

References

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.

Reference Type: DERIVED

PMID: 40668662 (View on PubMed)

Related Links

https://www.merckclinicaltrials.com/

Merck Clinical Trials Information

https://msd.trialsummaries.com/Study/StudyDetails?id=26283&tenant=MT_MSD_9011

Plain Language Summary

Other Identifiers

MK-4280-003

Identifier Type: OTHER

Identifier Source: secondary_id

2023-503587-17-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1287-5405

Identifier Type: REGISTRY

Identifier Source: secondary_id

2018-001461-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

4280-003

Identifier Type: -

Identifier Source: org_study_id