Study of Safety and Efficacy of Pembrolizumab and Chemotherapy in Participants With Newly Diagnosed Classical Hodgkin Lymphoma (cHL) (MK-3475-C11/KEYNOTE-C11) (KEYNOTE-C11)

Phase 2 Study of Pembrolizumab and Chemotherapy in Patients With Newly Diagnosed Classical Hodgkin Lymphoma (KEYNOTE-C11)

The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) monotherapy, followed by chemotherapy, followed by pembrolizumab consolidation. The primary hypothesis of the study is that the complete response (CR) rate at the end of study intervention according to Lugano 2014 response criteria is higher than conventional chemotherapy.

Study Overview

• Status: Completed
• Conditions: Classical Hodgkin Lymphoma
• Intervention / Treatment: Biological: Pembrolizumab; Drug: Doxorubicin; Drug: Vinblastine; Drug: Dacarbazine; Drug: Bleomycin; Drug: Etoposide; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Procarbazine; Drug: Prednisone

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital-Haematology ( Site 0906)
  • Queensland
    • Brisbane, Queensland, Australia, 4101
      • Mater Misericordiae Limited ( Site 0904)
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital-Division of Cancer Services Trials Unit ( Site 0907)
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health-Haematology Research ( Site 0908)
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre ( Site 0905)
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute ( Site 0207)
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre ( Site 0205)
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital ( Site 0200)
    • Montreal, Quebec, Canada, H4J 1C5
      • Hopital du Sacre-Coeur de Montreal ( Site 0206)
    • Montréal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre ( Site 0209)
• Chile
  • Araucania
    • Temuco, Araucania, Chile, 4780000
      • Centro Investigación del Cáncer James Lind ( Site 1200)
  • Region M. De Santiago
    • Chile, Region M. De Santiago, Chile, 8380455
      • Instituto Nacional del Cancer ( Site 1205)
    • Santiago, Region M. De Santiago, Chile, 6900941
      • FALP-UIDO ( Site 1202)
    • Santiago, Region M. De Santiago, Chile, 8320325
      • Clínica Alemana de Santiago ( Site 1206)
    • Santiago, Region M. De Santiago, Chile, 8330032
      • Pontificia Universidad Catolica de Chile-Hemato-Oncology ( Site 1204)
• France
  • Aquitaine
    • Pessac, Aquitaine, France, 33600
      • CHU Bordeaux Haut-Leveque ( Site 1505)
  • Bretagne
    • Rennes, Bretagne, France, 35033
      • Centre Hospitalier Universitaire de Rennes - Hôpital Pontchaillou-haematology ( Site 1502)
  • Cote-d Or
    • Dijon, Cote-d Or, France, 21000
      • Centre Hospitalier Universitaire Dijon Bourgogne - Hôpital François Mitterrand ( Site 1504)
  • Rhone
    • Pierre-Bénite, Rhone, France, 69310
      • centre hospitalier lyon sud-Service Hématologie ( Site 1501)
  • Seine-Maritime
    • Rouen, Seine-Maritime, France, 76000
      • Centre de Lutte Contre le Cancer - Centre Henri Becquerel Normandie Rouen-Service d'Hématologie ( Si
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus ( Site 1907)
  • Haifa, Israel, 3339419
    • Bnai Zion Medical Center-Hematology ( Site 1909)
  • Jerusalem, Israel, 9112001
    • Hadassah Medical Center ( Site 1901)
  • Ramat Gan, Israel, 5265601
    • Sheba Medical Center-Hemato Oncology ( Site 1904)
  • Safed, Israel, 1311001
    • ZIV Medical Center ( Site 1908)
  • Tel Aviv, Israel, 6423906
    • Sourasky Medical Center ( Site 1905)
• Italy
  • Bologna, Italy, 40138
    • Policlinico S. Orsola- Malpighi-Istituto di Ematologia L. e A. Seragnoli ( Site 1800)
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli-ISTITUTO DI EMATOLOGIA ( Site 1804)
  • Lombardia
    • Brescia, Lombardia, Italy, 25123
      • Azienda Ospedaliera Spedali Civili di Brescia-Hemathology ( Site 1801)
  • Milano
    • Milan, Milano, Italy
      • ASST Grande Ospedale Metropolitano Niguarda ( Site 1803)
• Poland
  • Mazowieckie
    • Warsaw, Mazowieckie, Poland, 02-776
      • Klinika Hematologii - Instytut Hematologii i Transfuzjologii-Klinika Hematologii ( Site 0402)
    • Warszawa, Mazowieckie, Poland, 02-781
      • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (
  • Opolskie
    • Opole, Opolskie, Poland, 46-020
      • Szpital Wojewódzki w Opolu-Hematology Department ( Site 0401)
  • Pomorskie
    • Gdańsk, Pomorskie, Poland, 80-952
      • Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 0403)
• Russian Federation
  • Moskva
    • Moscow, Moskva, Russian Federation, 125284
      • Moscow City Clinical Hospital S.P. Botkin ( Site 0702)
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 197022
      • First Pavlov State Medical University of Saint Petersburg-Raisa Gorbacheva Memorial Institut for Pe
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 197341
      • Almazov National Medical Research Centre ( Site 0704)
• Spain
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre ( Site 1032)
  • Barcelona
    • L'Hospitalet Del Llobregat, Barcelona, Spain, 08908
      • Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 1031)
• Turkey
  • Ankara, Turkey, 06100
    • Ankara University Hospital Cebeci-hematology ( Site 5000)
  • Istanbul, Turkey, 34365
    • Vehbi Koc Vakfi - Amerikan Hastanesi ( Site 5001)
  • Izmir
    • Balçova, Izmir, Turkey
      • Dokuz Eylül Üniversitesi ( Site 5002)
• United States
  • California
    • Fullerton, California, United States, 92835
      • St Joseph Heritage Healthcare-Oncology ( Site 0004)
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Center ( Site 0023)
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital ( Site 0002)
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • OptumCare Cancer Care-Research Department ( Site 0005)
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center-Cancer Institute ( Site 0006)
  • Texas
    • Plano, Texas, United States, 75075
      • Texas Oncology-Plano East ( Site 0020)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

The main inclusion criteria include, but are not limited to the following:

• Has a histologically confirmed diagnosis of Ann Arbor Stage III or IV classical Hodgkin Lymphoma (cHL). Stage I and II participants may be enrolled, but must have at least one National Comprehensive Cancer Network (NCCN) unfavorable risk factor per protocol
• Has measurable 2-fluorodeoxyglucose (FDG)-avid disease based on investigator assessment according to Lugano 2014 response criteria
• Has not received prior radiation therapy, chemotherapy, immunotherapy, or other systemic therapy for the treatment of cHL before the first dose of study intervention
• Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 assessed within 7 days before the start of study intervention

Exclusion Criteria:

The main exclusion criteria include, but are not limited to the following:

• Has confirmed nodular lymphocyte-predominant Hodgkin Lymphoma (HL)
• Has an uncontrolled intercurrent cardiovascular illness
• Has received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-programmed cell death ligand 1 protein (PD-L1), or anti- programmed cell death ligand 2 protein (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
• Has received or is expected to receive a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention
• 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 medication
• Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
• Has radiographically detectable central nervous system metastases and/or carcinomatous meningitis
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has a history or current evidence of pulmonary fibrosis
• Has had an allogenic tissue/solid organ transplant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pembrolizumab Monotherapy + AVD Chemotherapy/escBEACOPP Chemotherapy + Pembrolizumab Consolidation; After completing Positron Emission Tomography (PET) scan 1 during eligibility screening, participants received pembrolizumab monotherapy intravenous (IV) for three 3-week cycles followed by PET scan 2. Participants next received 2 phases of chemotherapy. In chemotherapy phase 1, all participants received doxorubicin in combination with vinblastine & dacarbazine (AVD) IV for two 4-week cycles followed by PET scan 3. In chemotherapy phase 2, participants who were PET scan 3 negative, or positive and age ≥60 years, received up to 4 additional cycles of AVD IV, while participants who were PET scan 3 positive and age <60 years received up to four 3-week cycles of escalated bleomycin in combination with etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, & prednisone (escBEACOPP) IV. All participants then received pembrolizumab consolidation IV for four 6-week cycles followed by a final PET scan.

Biological: Pembrolizumab; 200 mg IV administered on Day 1 of each 3-week cycle for 3 cycles during pembrolizumab monotherapy. 400 mg IV administered on Day 1 of each 6-week cycle for 4 cycles as pembrolizumab consolidation.; Other Names: MK-3475; SCH 900475; KEYTRUDA®; Drug: Doxorubicin; 25 mg/m^2 IV administered as part of AVD chemotherapy on Days 1 and 15 of each 4-week cycle for 2 cycles in all participants after PET scan 2 and up to 4 additional cycles after PET scan 3 (participants who are PET scan 3 negative, or positive and ≥60 years of age). 35 mg/m^2 IV administered as part of escBEACOPP chemotherapy on Day 1 of each 3-week cycle for up to 4 cycles after PET scan 3 (participants who are PET scan 3 positive, <60 years of age).; Other Names: Adriamycin; DOXIL®; Rubex®; Drug: Vinblastine; 6 mg/m^2 IV administered as part of AVD chemotherapy on Days 1 and 15 of each 4-week cycle for 2 cycles after PET scan 2 (all participants) and up to 4 additional cycles after PET scan 3 (participants who are PET scan 3 negative, or positive and ≥60 years of age).; Other Names: Velban®; Alkaban-AQ®; Drug: Dacarbazine; 375 mg/m^2 IV administered as part of AVD chemotherapy on Days 1 and 15 of each 4-week cycle for 2 cycles after PET scan 2 (all participants) and up to 4 additional cycles after PET scan 3 (participants who are PET scan 3 negative, or positive and ≥60 years of age).; Other Names: Dtic-Dome®; Drug: Bleomycin; 10 units/m^2 IV administered as part of escBEACOPP chemotherapy on Day 8 of each 3-week cycle for up to 4 cycles after PET scan 3 (participants who are PET scan 3 positive and <60 years of age).; Other Names: Blenoxane®; Drug: Etoposide; 200 mg/m^2 IV administered as part of escBEACOPP chemotherapy on Days 1-3 of each 3-week cycle for up to 4 cycles after PET scan 3 (participants who are PET scan 3 positive and <60 years of age).; Other Names: VP-16; VePesid®; Etopophos®; Toposar®; Etoposide phosphate; Drug: Cyclophosphamide; 1250 mg/m^2 IV administered as part of escBEACOPP chemotherapy on Day 1 of each 3-week cycle for up to 4 cycles after PET scan 3 (participants who are PET scan 3 positive and <60 years of age).; Other Names: Cytoxan®; Neosar®; Drug: Vincristine; 1.4 mg/m^2 IV administered as part of escBEACOPP chemotherapy on Day 8 of each 3-week cycle for up to 4 cycles after PET scan 3 (participants who are PET scan 3 positive and <60 years of age).; Other Names: Oncovin®; Vincasar PFS®; Drug: Procarbazine; 100 mg/m^2 orally (PO) administered as part of escBEACOPP chemotherapy on Days 1-7 of each 3-week cycle for up to 4 cycles after PET scan 3 (participants who are PET scan 3 positive and <60 years of age).; Other Names: Matulane®; Drug: Prednisone; 40 mg/m^2 PO administered as part of escBEACOPP chemotherapy on Days 1-14 of each 3-week cycle for up to 4 cycles after PET scan 3 (participants who are PET scan 3 positive and <60 years of age).; Other Names: Deltasone®; Orasone®; Liquid Pred®; Meticorten®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response (CR) Rate at the End of Study Intervention as Assessed by Blinded Independent Central Review (BICR) Per Lugano 2014 Response Criteria	CR rate was assessed by BICR using Computed Tomography (CT) and PET scan according to Lugano 2014 response criteria (Cheson, B.D. et al, Journal of Clinical Oncology, 2014). At each timepoint, CR was determined by combining the anatomic response, metabolic response, and clinical data. The criteria for CR included complete metabolic (no/minimal 2-fluorodeoxyglucose [FDG] uptake) and radiologic response (target lesions regress to ≤1.5 cm in longest transverse diameter of a lesion) and no new lesions. Per protocol, participants who discontinued study intervention during pembrolizumab monotherapy, chemotherapy, or pembrolizumab consolidation, or are lost to follow-up, or receive any new non-study anticancer therapy prior to end of treatment were classified as non-responders. The percentage of participants who had CR after the completion of pembrolizumab consolidation is presented.	Up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CR Rate at the End of Study Intervention as Assessed by Investigator Per Lugano 2014 Response Criteria	CR rate was assessed by the investigator using CT and PET scan according to Lugano 2014 response criteria (Cheson, B.D. et al, Journal of Clinical Oncology, 2014). At each timepoint, CR was determined by combining the anatomic response, metabolic response, and clinical data. The criteria for CR included complete metabolic (no/minimal FDG uptake) and radiologic response (target lesions regress to ≤1.5 cm in longest transverse diameter of a lesion) and no new lesions. Per protocol, participants who discontinued study intervention during pembrolizumab monotherapy, chemotherapy, or pembrolizumab consolidation, or are lost to follow-up, or receive any new non-study anticancer therapy prior to end of treatment were classified as non-responders. The percentage of participants who had CR after the completion of pembrolizumab consolidation is presented.	Up to approximately 31 months
Duration of Complete Response (DurCR) as Assessed by BICR Per Lugano 2014 Response Criteria	DurCR was defined as the time from CR to progressive disease (PD) or death due to any cause, whichever came first. CR was assessed by BICR using CT and PET scan according to Lugano 2014 response criteria (Cheson, B.D. et al, Journal of Clinical Oncology, 2014). At each timepoint, CR was determined by combining the anatomic response, metabolic response, and clinical data. The criteria for CR included complete metabolic (no/minimal FDG uptake) and radiologic response (target lesions regress to ≤1.5 cm in longest transverse diameter of a lesion) and no new lesions. PD was defined as uptake moderately or markedly higher than the liver and/or new lesions. DurCR was analyzed by the Kaplan-Meier method for censored data and is presented for participants who demonstrated CR.	Up to approximately 31 months
Rate of PET Negativity Assessed by BICR According to the FDG-PET 5-point Scale After Administration of Pembrolizumab Monotherapy (PET Scan 2)	The rate of PET negativity was defined as the percentage of participants considered negative on the FDG-PET 5-point scale, as assessed by BICR according to Lugano 2014 response criteria (Cheson, B.D. et al, Journal of Clinical Oncology, 2014). Participants were assigned a single score on the FDG-PET 5-point scale measuring FDG uptake (1 = no uptake above background, 2 = uptake above background but ≤ mediastinum, 3 = uptake > mediastinum but ≤ liver, 4 = uptake moderately > liver, 5 = uptake markedly > liver or new FDG-positive lesions). Higher scores corresponded to greater uptake (greater disease). FDG-PET 5-point scale scores of 1, 2, and 3 were considered negative and scores of 4 and 5 were considered positive. The percentage of participants who were assessed as negative at PET scan 2, after completion of 3 cycles of pembrolizumab monotherapy, is presented.	Up to approximately 10 weeks
Rate of PET Negativity Assessed by BICR According to the FDG-PET 5-point Scale After Administration of Pembrolizumab Monotherapy and AVD Chemotherapy (PET Scan 3)	The rate of PET negativity was defined as the percentage of participants considered negative on the FDG-PET 5-point scale, as assessed by BICR according to Lugano 2014 response criteria (Cheson, B.D. et al, Journal of Clinical Oncology, 2014). Participants were assigned a single score on the FDG-PET 5-point scale measuring FDG uptake (1 = no uptake above background, 2 = uptake above background but ≤ mediastinum, 3 = uptake > mediastinum but ≤ liver, 4 = uptake moderately > liver, 5 = uptake markedly > liver or new FDG-positive lesions). Higher scores corresponded to greater uptake (greater disease). FDG-PET 5-point scale scores of 1, 2, and 3 were considered negative and scores of 4 and 5 were considered positive. The percentage of participants who were assessed as negative at PET scan 3, after completion of 3 cycles of pembrolizumab monotherapy and phase 1 AVD chemotherapy (2 AVD cycles), is presented.	Up to approximately 5 months
Number of Participants Who Experienced 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Per protocol, collection and reporting of AEs was based on the study treatment received by the participant (pembrolizumab, AVD chemotherapy, or escBEACOPP chemotherapy) at the time of the event. The number of participants who experienced an AE is reported.	Up to approximately 31 months
Number of Participants Who Discontinued Study Treatment Due to an 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Per protocol, collection and reporting of AEs was based on the study treatment received by the participant (pembrolizumab, AVD chemotherapy, or escBEACOPP chemotherapy) at the time of the event. The number of participants who discontinued study intervention due to an AE is reported.	Up to approximately 17 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Allen PB, Lu X, Chen Q, O'Shea K, Chmiel JS, Slonim LB, Sukhanova M, Savas H, Evens AM, Advani R, Pro B, Karmali R, Palmer B, Bayer RA, Eisner RM, Mou E, Dillehay G, Gordon LI, Winter JN. Sequential pembrolizumab and AVD are highly effective at any PD-L1 expression level in untreated Hodgkin lymphoma. Blood Adv. 2023 Jun 27;7(12):2670-2676. doi: 10.1182/bloodadvances.2022008116.

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2021
• Primary Completion (Actual): October 11, 2023
• Study Completion (Actual): May 26, 2024

Study Registration Dates

• First Submitted: August 13, 2021
• First Submitted That Met QC Criteria: August 13, 2021
• First Posted (Actual): August 17, 2021

Study Record Updates

• Last Update Posted (Actual): June 6, 2025
• Last Update Submitted That Met QC Criteria: May 23, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Programmed Cell Death 1 (PD-1, PD1); Programmed Cell Death-Ligand 1 (PD-L1, PDL1); Programmed Cell Death-Ligand 2 (PD-L2, PDL2)
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antibiotics, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Enzyme Inhibitors; Antirheumatic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase Inhibitors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Prednisone; Cyclophosphamide; Etoposide; Pembrolizumab; Doxorubicin; Vincristine; Dacarbazine; Vinblastine; Etoposide phosphate; Bleomycin; Procarbazine
• Other Study ID Numbers: 3475-C11; MK-3475-C11 (Other Identifier: MSD); KEYNOTE-C11 (Other Identifier: MSD); 2021-001244-95 (EudraCT Number); 2022-501615-14-00 (Registry Identifier: EU CT); U1111-1281-5347 (Registry Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/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