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Hodgkin DiseasePhase 1/2NCT03598608

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)

A Phase 1/2 study testing pembrolizumab and Favezelimab in people with Hodgkin Disease and Lymphoma, Non-Hodgkin, run by Merck Sharp & Dohme LLC at 25 sites in 6 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
pembrolizumab and Favezelimab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
137 participants
Where
25 sitesin 6 countries
Study dates
17 Oct 2018to 28 Jan 2026
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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
Show all 17Show fewer
  • 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

Trial locations and contacts

25 sites in 6 countries.

25 sites in 6 countries

United States8 sites

  • Texas Oncology-Austin Midtown ( Site 8002)

    Austin, Texas, 78705

  • Dana Farber Cancer Institute ( Site 0002)

    Boston, Massachusetts, 02215

  • City of Hope ( Site 0001)

    Duarte, California, 91010

  • Banner MD Anderson Cancer Center ( Site 0020)

    Gilbert, Arizona, 85234

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

    Los Angeles, California, 90095

  • Pacific Cancer Care ( Site 0006)

    Monterey, California, 93940

  • Fox Chase Cancer Center ( Site 0019)

    Philadelphia, Pennsylvania, 19111

  • University of California San Francisco ( Site 0023)

    San Francisco, California, 94143

Other trials in United States

Australia4 sites

  • Monash Health ( Site 0201)

    Clayton, Victoria, 3168

  • Concord Repatriation & General Hospital ( Site 0203)

    Concord, New South Wales, 2139

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

    Fitzroy, Victoria, 3065

  • Princess Alexandra Hospital ( Site 0204)

    Woollongabba, Queensland, 4102

Other trials in Australia

Canada4 sites

  • Jewish General Hospital ( Site 0105)

    Montreal, Quebec, H3T 1E2

  • Princess Margaret Cancer Centre ( Site 0100)

    Toronto, Ontario, M5G 2M9

  • BC Cancer ( Site 0107)

    Vancouver, British Columbia, V5Z 1L3

  • CancerCare Manitoba ( Site 0101)

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

Israel4 sites

  • Rambam Medical Center ( Site 0382)

    Haifa, 3109601

  • Hadassah Ein Karem Jerusalem ( Site 0383)

    Jerusalem, 9112001

  • Chaim Sheba Medical Center. ( Site 0380)

    Ramat Gan, 5262001

  • Sourasky Medical Center ( Site 0381)

    Tel Aviv, 6423906

Other trials in Israel

Italy3 sites

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

    Bologna, Emilia-Romagna, 40138

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

    Meldola, Forli-Cesena, 47014

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

    Rozzano, Milano, 20089

Other trials in Italy

Germany2 sites

  • U. klinikum Koeln AOER ( Site 0326)

    Cologne, North Rhine-Westphalia, 50937

  • Universitaetsklinikum Leipzig AOeR ( Site 0327)

    Leipzig, Saxony, 4103

Other trials in Germany

About this study

Official title: A Phase 1/Phase 2 Clinical Study to Evaluate the Safety and Efficacy of a Combination of MK-4280 and Pembrolizumab (MK-3475) in Participants With Hematologic Malignancies

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)
Read more

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.

Read the detailed description

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

Being tested
pembrolizumab, Favezelimab
Keywords
programmed cell death 1 (PD-1, PD1), programmed cell death ligand 1 (PD-L1, PDL1), programmed cell death ligand 2 (PD-L2, PDL2)
Medical subject headings
Hodgkin Disease, Lymphoma, Non-Hodgkin, Lymphoma, B-Cell, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • pembrolizumabBiological

    Also called KEYTRUDA®, MK-3475

    Administered as an IV infusion every 3 weeks (Q3W)

  • FavezelimabBiological

    Also called MK-4280

    Administered as an IV infusion Q3W

Study groups in NCT03598608
Study groupRoleWhat they receive
Part A: Favezelimab Dose A+pembrolizumabExperimentalParticipants 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).
Receives: Biological: pembrolizumab; Biological: Favezelimab
Part A: Favezelimab Dose B+pembrolizumabExperimentalParticipants 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).
Receives: Biological: pembrolizumab; Biological: Favezelimab
Part A: Favezelimab Dose C+PembrolizumabExperimentalParticipants 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).
Receives: Biological: pembrolizumab; Biological: Favezelimab
Part B: cHL-Combination TherapyExperimentalParticipants 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).
Receives: Biological: pembrolizumab; Biological: Favezelimab
Part B: DLBCL-Combination TherapyExperimentalParticipants 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).
Receives: Biological: pembrolizumab; Biological: Favezelimab
Part B: iNHL-Combination TherapyExperimentalParticipants 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).
Receives: Biological: pembrolizumab; Biological: Favezelimab
Part B: Randomized cHL-MonotherapyExperimentalParticipants 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).
Receives: Biological: pembrolizumab; Biological: Favezelimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Cycle 1 (up to 21 days)

  2. 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

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

  3. Percentage of Participants with Treatment Discontinuations Due to an AE

    Percentage of participants discontinuing study treatment due to an AE

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

Secondary outcomes (1)

  1. Objective Response Rate (ORR)

    ORR is defined as the percentage of participants in the analysis population who had a Complete Response or a Partial Response per lymphoma disease response criteria (Cheson et. al., 2007) as assessed by the investigator.

    Measured: Up to approximately 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jul 2018
  2. Study start17 Oct 2018
  3. Primary completion28 Jan 2026
  4. Study completion28 Jan 2026

Why it stopped: Business Reason

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
137 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03598608
Sponsor's protocol ID
4280-003
Other IDs
MK-4280-003, 2023-503587-17-00, U1111-1287-5405, 2018-001461-16, 2018, 2023
Status last verified
Jul 2026
First submitted
16 Jul 2018
Last updated
28 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

  • Johnson NA, Lavie D, Borchmann P, Gregory GP, Herrera AF, Minuk L, Vucinic V, Armand P, Avigdor A, Gasiorowski R, Herishanu Y, Keane C, Kuruvilla J, Marceu West R, Pillai PM, Marinello P, Timmerman JM. Phase 1/2 study of favezelimab plus pembrolizumab in anti-PD-1-naive relapsed or refractory classical Hodgkin lymphoma. Blood Adv. 2026 Oct 2:bloodadvances.2025018506. doi: 10.1182/bloodadvances.2025018506. Online ahead of print.

    PubMed 42826707

  • Timmerman J, Lavie D, Johnson NA, Avigdor A, Borchmann P, Andreadis C, Bazargan A, Gregory GP, Keane C, Tzoran I, Vucinic V, Zinzani PL, West RM, Pillai P, Marinello P, Herrera AF. Favezelimab plus pembrolizumab for anti-PD-1-refractory classic Hodgkin lymphoma: an open-label phase 1/2 study. Blood Neoplasia. 2026 May 26;3(4):100252. doi: 10.1016/j.bneo.2026.100252. eCollection 2026 Nov.

    PubMed 42699247

  • 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.

    PubMed 40668662

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing pembrolizumab and Favezelimab in people with Hodgkin Disease and Lymphoma, Non-Hodgkin, run by Merck Sharp & Dohme LLC at 25 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 28 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States, Australia, Canada, Israel, Italy and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Business Reason). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Experiencing a Dose-limiting Toxicity (DLT) (time frame: Cycle 1 (up to 21 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03598608, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2026; AzTrials last refreshed its copy on 6 Nov 2026.

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