A Study of Coformulated Favezelimab/Pembrolizumab (MK-4280A) Versus Physician's Choice Chemotherapy in PD-(L)1-refractory, Relapsed or Refractory Classical Hodgkin Lymphoma (MK-4280A-008)

A Phase 2 Randomized Clinical Study of MK-4280A (Coformulated Favezelimab [MK-4280] Plus Pembrolizumab [MK-3475]) Versus Physician's Choice Chemotherapy in PD-(L)1-refractory, Relapsed or Refractory Classical Hodgkin Lymphoma (KEYFORM-008)

Researchers are looking for a way to treat classical Hodgkin lymphoma (cHL) that is relapsed (the cancer has come back after treatment) or refractory (current treatment has stopped working to slow or stop cancer growth). Researchers want to learn if people who receive coformulated favezelimab/pembrolizumab (MK-4280A) live longer without the cancer getting worse compared to those who receive chemotherapy.

Study Overview

• Status: Completed
• Conditions: Hodgkin Lymphoma
• Intervention / Treatment: Biological: favezelimab/pembrolizumab; Drug: bendamustine; Drug: gemcitabine

• Study Type: Interventional
• Enrollment (Actual): 203
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1118AAT
    • Hospital Aleman-oncohematologic diseases ( Site 2302)
  • Mendoza, Argentina, M5500AYB
    • Fundacion Centro Oncologico de Integración Regional-Medical Oncology ( Site 2301)
• Australia
  • Queensland
    • Townsville, Queensland, Australia, 4814
      • The Townsville Hospital ( Site 0006)
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital ( Site 0005)
  • Victoria
    • St Albans, Victoria, Australia, 3021
      • Western Health-Sunshine & Footscray Hospitals-Cancer Services-Cancer Research ( Site 0002)
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital-Haematology ( Site 0004)
• Belgium
  • Namur, Belgium, 5530
    • Université Catholique de Louvain-Namur - Centre Hospitalier Universitaire Dinant-Godinne - Site Godi
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • UZ Leuven-Hematology ( Site 0101)
• Brazil
  • São Paulo, Brazil, 01321-001
    • Hospital Paulistano-Americas Oncologia ( Site 0207)
  • São Paulo
    • Barretos, São Paulo, Brazil, 14784400
      • Fundação Pio XII - Hospital de Câncer de Barretos ( Site 0202)
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute ( Site 0313)
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre ( Site 0310)
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital ( Site 0309)
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre ( Site 0314)
• Chile
  • Region M. de Santiago
    • Santiago, Region M. de Santiago, Chile, 7500921
      • FALP-UIDO ( Site 0400)
    • Santiago, Region M. de Santiago, Chile, 7580206
      • Clínica Inmunocel ( Site 0407)
• China
  • Anhui
    • Hefei, Anhui, China, 230031
      • Anhui Provincial Cancer Hospital ( Site 0501)
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100005
      • Beijing Hospital ( Site 0514)
    • Beijing, Beijing Municipality, China, 100091
      • Peking University Third Hospital-Hematology ( Site 0519)
  • Fujian
    • Xiamen, Fujian, China, 361003
      • The First Affiliated hospital of Xiamen University ( Site 0512)
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center ( Site 0500)
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital ( Site 0515)
  • Hubei
    • Wuhan, Hubei, China, 430010
      • Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 0509)
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital Central South University ( Site 0513)
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital ( Site 0503)
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University-Hematology ( Site 0516)
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Fudan University Shanghai Cancer Center ( Site 0520)
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital of Sichuan University-Head and Neck Oncology ( Site 0502)
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300060
      • Tianjin Medical University Cancer Institute & Hospital-lymphoma ( Site 0506)
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital ( Site 0510)
    • Ningbo, Zhejiang, China, 315010
      • Ningbo First Hospital ( Site 0518)
• Czechia
  • Hradec Králové, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove-IV. interni hematologicka klinika ( Site 0902)
  • Prague, Czechia, 128 08
    • Vseobecna fakultni nemocnice v Praze-I. Interní klinika - klinika hematologie ( Site 0903)
  • Brno-mesto
    • Brno, Brno-mesto, Czechia, 625 00
      • Fakultní nemocnice Brno Bohunice-Interni hematologicka a onkologicka klinika ( Site 0901)
• France
  • Brittany Region
    • Rennes, Brittany Region, France, 35033
      • Centre Hospitalier Universitaire de Rennes - Hôpital Pontchaillou-haematology ( Site 0707)
  • Haute-Garonne
    • Toulouse, Haute-Garonne, France, 31059
      • Institut Universitaire du Cancer Toulouse - Oncopole - CHU de TOULOUSE ( Site 0706)
  • Haute-Vienne
    • Limoges, Haute-Vienne, France, 87042
      • Centre Hospitalier Universitaire de Limoges - Hôpital Dupuytren ( Site 0704)
  • Hauts-de-Seine
    • Saint-Cloud, Hauts-de-Seine, France, 92210
      • Institut Curie - site Saint-Cloud ( Site 0708)
  • Rhone
    • Lyon, Rhone, France, 69008
      • CENTRE LEON BERARD-Medical oncology ( Site 0703)
  • Seine-et-Marne
    • Créteil, Seine-et-Marne, France, 94000
      • HENRI MONDOR HOSPITAL ( Site 0702)
• Germany
  • Baden-Wurttemberg
    • Stuttgart, Baden-Wurttemberg, Germany, 70174
      • Klinikum Stuttgart - Katharinenhospital ( Site 0804)
    • Ulm, Baden-Wurttemberg, Germany, 89081
      • Universitaetsklinikum Ulm-Department of Internal Medicine III ( Site 0805)
  • North Rhine-Westphalia
    • Cologne, North Rhine-Westphalia, Germany, 50937
      • Universitaetsklinikum Koeln-Klinik I für Innere Medizin ( Site 0801)
    • Essen, North Rhine-Westphalia, Germany, 45147
      • Universitaetsklinikum Essen ( Site 0807)
    • Münster, North Rhine-Westphalia, Germany, 48149
      • Universitätsklinikum Münster - Albert Schweitzer Campus ( Site 0806)
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Universitaetsklinikum Carl Gustav Carus Dresden-University Cancer Center Early Clinical Trial Unit (
    • Leipzig, Saxony, Germany, 04103
      • Universitätsklinikum Leipzig ( Site 0803)
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus ( Site 1004)
  • Haifa, Israel, 3436212
    • Carmel Hospital ( Site 1007)
  • Jerusalem, Israel, 9112001
    • Hadassah Medical Center-Hemato-Oncology ( Site 1000)
  • Petah Tikva, Israel, 4910021
    • Rabin Medical Center-Hemato-Oncology ( Site 1001)
  • Ramat Gan, Israel, 5265601
    • Sheba Medical Center-Hemato Oncology ( Site 1005)
  • Tel Aviv, Israel, 6423906
    • Sourasky Medical Center ( Site 1002)
• Mexico
  • Puebla City, Mexico, 72424
    • Unidad Médica Onco-hematológica ( Site 2507)
  • Mexico City
    • Mexico City, Mexico City, Mexico, 03100
      • Centro de Infusion Superare ( Site 2503)
• Poland
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 31-826
      • Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie-Oncology Department ( Site 1406)
  • Lower Silesian Voivodeship
    • Wroclaw, Lower Silesian Voivodeship, Poland, 50-556
      • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckieg-Klinika Hematologii, Nowotworów Krwi i
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-781
      • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Kilinka Onkologii I Hematologii ( Site
  • Pomeranian Voivodeship
    • Gdansk, Pomeranian Voivodeship, Poland, 80-214
      • Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 1402)
  • Świętokrzyskie Voivodeship
    • Kielce, Świętokrzyskie Voivodeship, Poland, 25-734
      • Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zakl-Klinika Hematologii i Transplantacji S
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital ( Site 1701)
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1702)
  • Seoul, South Korea, 05505
    • Asan Medical Center-Department of Oncology ( Site 1703)
  • Seoul, South Korea, 06351
    • Samsung Medical Center ( Site 1700)
  • Pusan-Kwangyokshi
    • Busan, Pusan-Kwangyokshi, South Korea, 49241
      • Pusan National University Hospital-Internal Medicine ( Site 1704)
• Spain
  • Alicante, Spain, 03010
    • Hospital General Universitario de Alicante ( Site 1806)
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre-Hemathology and hemotherapy ( Site 1810)
  • Málaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria ( Site 1808)
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca - Complejo Asistencial U-Servicio de Hematologia ( Site 1801)
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marqués de Valdecilla ( Site 1805)
  • Catalonia
    • Barcelona, Catalonia, Spain, 08035
      • Hospital Universitari Vall d'Hebron ( Site 1803)
  • La Coruna
    • A Coruña, La Coruna, Spain, 15006
      • CHUAC-Complejo Hospitalario Universitario A Coruña ( Site 1812)
  • Las Palmas
    • Las Palmas de Gran Canaria, Las Palmas, Spain, 35016
      • Hospital Insular de Gran Canaria-Oncology ( Site 1807)
• Sweden
  • Skåne County
    • Lund, Skåne County, Sweden, 22185
      • Skånes Universitetssjukhus Lund ( Site 1901)
  • Uppsala County
    • Uppsala, Uppsala County, Sweden, 751 85
      • Akademiska sjukhuset-Blod- och tumörsjukdomar ( Site 1900)
• Switzerland
  • Canton Ticino
    • Bellinzona, Canton Ticino, Switzerland, 6501
      • Ospedale Regionale Bellinzona e Valli-IOSI ( Site 1600)
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06100
    • Ankara Universitesi Tip Fakultesi Hastanesi-hematology ( Site 2000)
  • Ankara, Turkey (Türkiye), 06230
    • Hacettepe Universite Hastaneleri-Department of Hematology ( Site 2006)
  • Antalya, Turkey (Türkiye), 07100
    • Antalya Egitim ve Arastırma Hastanesi ( Site 2011)
  • Izmir, Turkey (Türkiye), 35100
    • Ege Universitesi Hastanesi ( Site 2001)
  • Kocaeli, Turkey (Türkiye), 41380
    • Kocaeli Üniversitesi-Hematology ( Site 2009)
  • Istanbul
    • Stanbul, Istanbul, Turkey (Türkiye), 34214
      • Mega Medipol-Hematology ( Site 2005)
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • St James's University Hospital ( Site 2109)
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary ( Site 2100)
  • Liverpool, United Kingdom, L7 8YA
    • Clatterbridge Cancer Centre - Liverpool-Heamatology ( Site 2108)
  • Devon
    • Plymouth, Devon, United Kingdom, Pl6 8DH
      • Derriford Hospital ( Site 2107)
  • Glasgow City
    • Glasgow, Glasgow City, United Kingdom, G12 0YN
      • The Beatson West of Scotland Cancer Centre ( Site 2110)
  • London, City of
    • London, London, City of, United Kingdom, EC1A 7BE
      • St Bartholomew's Hospital-Centre for Experimental Cancer Medicine ( Site 2105)
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX4 6LB
      • GenesisCare - Oxford ( Site 2104)
• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • The University of Arizona Cancer Center - North Campus ( Site 2216)
  • California
    • Los Angeles, California, United States, 90404
      • UCLA Hematology/Oncology - Santa Monica ( Site 2208)
    • Torrance, California, United States, 90502
      • Lundquist Institute for Biomedical Innovation at Harbor-UCLA-Hematology and Medical Oncology ( Site
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center ( Site 2200)
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Chandler Medical Center ( Site 2201)
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland-Greenebaum Comprehensive Cancer Center ( Site 2210)
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins University-The Sidney Kimmel Comprehensive Cancer Center ( Site 2206)
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan ( Site 2215)
    • Grand Rapids, Michigan, United States, 49503
      • Cancer and Hematology Centers of Western Michigan ( Site 2222)
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey ( Site 2217)
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute ( Site 2220)
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center ( Site 2214)
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic-Taussig Cancer Center ( Site 2203)
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • AHN West Penn Hospital ( Site 2213)
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center ( Site 2205)
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Center ( Site 2212)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has histologically confirmed diagnosis of classical Hodgkin lymphoma (cHL) that is 2-fluorodeoxyglucose-avid (FDG-avid).
• Has relapsed (defined as disease progression after most recent therapy) or refractory (defined as failed to achieve CR or PR to most recent therapy) cHL and exhausted all available treatment options with known clinical benefit.
• Has progressed on treatment with an anti-PD-(L)1 monoclonal antibody (mAb) administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies.
• Submits an archival (≤5 years) or newly obtained tumor tissue sample which has not been previously irradiated.

Exclusion Criteria:

• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy.
• History of central nervous system (CNS) metastases or active CNS involvement.
• Has an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy.
• History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic treatment.
• History of hemophagocytic lymphohisticytosis.
• Has an active seizure disorder that is not well controlled.
• Has clinically significant (ie, active) cardiovascular disease.
• Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
• Received prior radiotherapy within 2 weeks of start of study intervention or radiation related toxicities requiring corticosteroids.
• Has not adequately recovered from major surgical procedure.
• Known additional malignancy that is progressing or has required active treatment within the past 3 years.
• History of human immunodeficiency virus (HIV).
• Has had an allogeneic hematopoietic stem cell or solid organ transplantation within the last 5 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Favezelimab/Pembrolizumab; Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) by intravenous (IV) infusion on Day 1, then every three weeks (Q3W), for up to 35 infusions.	Biological: favezelimab/pembrolizumab; Coformulated favezelimab/pembrolizumab (800 mg/200 mg), IV infusion; Other Names: MK-4820A
Active Comparator: Chemotherapy (Bendamustine or Gemcitabine); Participants will receive physician's choice of EITHER bendamustine by IV infusion at a dose between 90 and 120 mg/m^2 on Day 1 and Day 2 of either a 3- or 4-week cycle for up to 6 cycles OR gemcitabine by IV infusion at a dose between 800 and 1200 mg/m^2 on Day 1 and Day 8 of a 3-week cycle for up to 6 cycles.	Drug: bendamustine; IV infusion; Other Names: BENDEKA®; Drug: gemcitabine; IV infusion; Other Names: GEMZAR®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) per Lugano Response Criteria as Assessed by investigator	PFS is defined as the time from randomization to the first documented disease progression per Lugano criteria 2014 as assessed by investigator or death due to any cause, whichever occurs first.	Up to approximately 39 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be presented.	Up to approximately 24 months
Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to approximately 39 months
Objective Response Rate (ORR) per Lugano Response Criteria as Assessed by investigator	ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) per Lugano criteria 2014 as assessed by investigator.	Up to approximately 39 months
Duration of Response (DOR) per Lugano Response Criteria as Assessed by investigator	For participants who demonstrate CR or PR per Lugano criteria 2014 as assessed by investigator, DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.	Up to approximately 39 months
Number of Participants Who Experienced At Least One Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be presented.	Up to approximately 25 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2022
• Primary Completion (Actual): September 3, 2025
• Study Completion (Actual): January 8, 2026

Study Registration Dates

• First Submitted: August 18, 2022
• First Submitted That Met QC Criteria: August 18, 2022
• First Posted (Actual): August 19, 2022

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 16, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• 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)
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Hemic and Lymphatic Diseases; Hodgkin Disease; Parkinson Disease 4, Autosomal Dominant Lewy Body; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Acids, Acyclic; Carboxylic Acids; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Butyrates; Bendamustine Hydrochloride; Gemcitabine; pembrolizumab
• Other Study ID Numbers: 4280A-008; MK-4280A-008 (Other Identifier: MSD); 2022-000371-39 (EudraCT Number); U1111-1287-5864 (Registry Identifier: UTN); 2023-503615-14-00 (Registry Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No