Safety and Efficacy of Pembrolizumab (MK-3475) in Children and Young Adults With Classical Hodgkin Lymphoma (MK-3475-667/KEYNOTE-667)

An Open-label, Uncontrolled, Multicenter Phase II Trial of MK-3475 (Pembrolizumab) in Children and Young Adults With Newly Diagnosed Classical Hodgkin Lymphoma With Inadequate (Slow Early) Response to Frontline Chemotherapy (KEYNOTE 667)

This study will examine the safety and efficacy of pembrolizumab (MK-3475) in combination with chemotherapy in children and young adults with newly diagnosed classical Hodgkin Lymphoma (cHL) who are slow early responders (SERs) to frontline chemotherapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Hodgkin Lymphoma
• Intervention / Treatment: Biological: pembrolizumab; Drug: doxorubicin; Drug: vinblastine; Drug: dacarbazine; Drug: bleomycin; Radiation: Radiotherapy (RT); Drug: cyclophosphamide; Drug: vincristine; Drug: prednisone/prednisolone; Drug: etoposide

Detailed Description

Group 1 will consist of low-risk participants with cHL Stages IA, IB and IIA without bulky disease. Group 2 will consist of high-risk participants with cHL Stages IIEB, IIIEA, IIIEB, IIIB, IVA and IVB.

• Study Type: Interventional
• Enrollment (Estimated): 340
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@merck.com

Study Locations

• Brazil
  • Sao Paulo, Brazil, 04023-062
    • Instituto de Oncologia Pediatrica - GRAACC - Unifesp ( Site 0500)
  • Parana
    • Curitiba, Parana, Brazil, 81520-060
      • Hospital Erasto Gaertner-CEPEP - Pesquisa Clínica ( Site 0507)
  • Rio Grande Do Norte
    • Natal, Rio Grande Do Norte, Brazil, 59075-740
      • Liga Norte Riograndense Contra o Câncer-Centro de Pesquisa Clínica ( Site 0510)
• Colombia
  • Antioquia
    • Medellin, Antioquia, Colombia, 05034
      • Hospital Pablo Tobon Uribe-Hematology ( Site 0565)
  • Atlantico
    • Barranquilla, Atlantico, Colombia, 080020
      • Organizacion Clinica Bonnadona-Prevenir S.A.S. ( Site 0529)
  • Cordoba
    • Monteria, Cordoba, Colombia, 230001
      • Oncomédica S.A.S ( Site 0527)
  • Distrito Capital De Bogota
    • Bogotá, Distrito Capital De Bogota, Colombia, 111511
      • Instituto Nacional De Cancerologia ( Site 0566)
• Czechia
  • Praha 5, Czechia, 150 06
    • Fakultni nemocnice v Motole ( Site 0356)
• France
  • Paris, France, 75012
    • Hopital d'Enfants Armand Trousseau ( Site 0443)
  • Paris, France, 75019
    • Hopital Universitaire Robert Debre ( Site 0446)
  • Bouches-du-Rhone
    • Marseille, Bouches-du-Rhone, France, 13005
      • CHU de Marseille Hopital de la Timone Enfants ( Site 0449)
  • Gironde
    • Bordeaux, Gironde, France, 33000
      • CHU de Bordeaux. Hopital Pellegrin ( Site 0447)
  • Nord
    • Lille, Nord, France, 59037
      • Hôpital Jeanne de Flandre ( Site 0450)
  • Rhone-Alpes
    • Lyon, Rhone-Alpes, France, 69008
      • Institut d'Hematologie-Oncologie Pediatrique (IHOP) ( Site 0448)
  • Val-de-Marne
    • Villejuif, Val-de-Marne, France, 94800
      • Institut Gustave Roussy ( Site 0445)
• Germany
  • Berlin, Germany, 13353
    • Charite-Universitaetsmedizin Berlin Campus Virchow-Klinikum ( Site 0413)
  • Bayern
    • Muenchen, Bayern, Germany, 80337
      • Klinikum der Universitaet Muenchen-Campus Innenstadt ( Site 0414)
  • Hessen
    • Giessen, Hessen, Germany, 35392
      • Universitaetsklinikum Giessen und Marburg GmbH ( Site 0411)
  • Nordrhein-Westfalen
    • Essen, Nordrhein-Westfalen, Germany, 45147
      • Universitaetsklinikum Essen ( Site 0415)
    • Münster, Nordrhein-Westfalen, Germany, 48149
      • Universitätsklinikum Münster - Albert Schweitzer Campus-Pädiatrische Hämatologie und Onkologie ( Sit
• Greece
  • Attiki
    • Athens, Attiki, Greece, 115 27
      • Athens Childrens Hospital Aglaia Kyriakou ( Site 0361)
    • Athens, Attiki, Greece, 115 27
      • University of Athens - Aghia Sophia Childrens Hospital ( Site 0362)
  • Kentriki Makedonia
    • Thessaloniki, Kentriki Makedonia, Greece, 546 36
      • University General Hospital of Thessaloniki "AHEPA" ( Site 0363)
• Guatemala
  • Guatemala, Guatemala, 01010
    • Oncomedica ( Site 0545)
  • Guatemala, Guatemala, 01011
    • Unidad Nacional de Oncologia Pediatrica ( Site 0542)
  • Guatemala, Guatemala, 01016
    • Medi-K Cayala ( Site 0544)
• Italy
  • Napoli, Italy, 80123
    • Azienda Ospedaliera Santobono - Pausilipon ( Site 0402)
  • Roma, Italy, 00165
    • IRCCS Ospedale Pediatrico Bambino Gesu ( Site 0400)
  • Torino, Italy, 10126
    • Ospedale Infantile Regina Margherita ( Site 0401)
  • Abruzzo
    • Roma, Abruzzo, Italy, 00161
      • Universita degli Studi di Roma La Sapienza ( Site 0403)
  • Pordenone
    • Aviano, Pordenone, Italy, 33081
      • Centro di Riferimento Oncologico CRO ( Site 0404)
• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital Yonsei University Health System ( Site 0221)
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center ( Site 0222)
• Mexico
  • Azcapotzalco, Mexico, 02990
    • UMAE Hospital de Especialidades - CMN La Raza ( Site 0536)
  • Huixquilucan, Mexico, 52787
    • Hematologica Alta Especialidad ( Site 0532)
  • Distrito Federal
    • Mexico D.F., Distrito Federal, Mexico, 06720
      • Hospital Infantil de Mexico Federico Gomez ( Site 0535)
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Hospital Universitario "Dr. Jose Eleuterio Gonzalez" ( Site 0531)
• Netherlands
  • Utrecht, Netherlands, 3584 CS
    • Prinses Maxima Centrum ( Site 0461)
• Slovakia
  • Bratislavsky Kraj
    • Bratislava, Bratislavsky Kraj, Slovakia, 833 40
      • Narodny ustav detskych chorob ( Site 0372)
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2193
      • Wits Clinical Research ( Site 0323)
    • Pretoria, Gauteng, South Africa, 0044
      • Albert Alberts Stem Cell Transplant Centre ( Site 0324)
    • Soweto, Gauteng, South Africa, 2193
      • Wits Clinical Research ( Site 0321)
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d Hebron ( Site 0432)
  • Madrid, Spain, 28009
    • Hospital Infantil Universitario Nino Jesus ( Site 0433)
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz ( Site 0434)
• United Kingdom
  • London, City Of
    • London, London, City Of, United Kingdom, NW1 2PG
      • University College London Hospitals NHS Foundation Trust ( Site 0454)
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Children's Hospital of Alabama ( Site 0023)
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Childrens Hospital ( Site 0034)
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital ( Site 0046)
  • California
    • Anaheim, California, United States, 92806
      • Kaiser - Orange County ( Site 0084)
    • Downey, California, United States, 90242
      • Kaiser Permanente ( Site 0082)
    • Fontana, California, United States, 92335
      • Kaiser - Fontana ( Site 0083)
    • Long Beach, California, United States, 90806
      • MemorialCare Health System - Long Beach Medical Center-Cherese Mari Laulhere Children's Village ( Si
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Downey Medical Center ( Site 0024)
    • Oakland, California, United States, 94611
      • Kaiser Permanente - Oakland ( Site 0047)
    • Roseville, California, United States, 95661
      • Kaiser Permanente - Roseville ( Site 0080)
    • Santa Clara, California, United States, 95051
      • Kaiser Permanente - Santa Clara ( Site 0079)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital - Colorado ( Site 0028)
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Connecticut Children's Medical Center ( Site 0045)
    • New Haven, Connecticut, United States, 06510
      • Yale Cancer Center ( Site 0061)
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center ( Site 0090)
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida ( Site 0051)
    • Hollywood, Florida, United States, 33021
      • Memorial Regional Hospital/Joe DiMaggio Children's Hospital ( Site 0048)
    • Orlando, Florida, United States, 32806
      • Arnold Palmer Hospital ( Site 0065)
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta at Egleston ( Site 0033)
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago ( Site 0066)
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children ( Site 0091)
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0293
      • University of Kentucky Markey Cancer Center ( Site 0057)
    • Louisville, Kentucky, United States, 40202
      • University of Louisville-Norton Children's Hospital ( Site 0059)
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University ( Site 0025)
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan ( Site 0056)
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute ( Site 0002)
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Hospitals and Clinics of Minnesota ( Site 0036)
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • St. Louis Children's Hospital ( Site 0038)
  • Nevada
    • Las Vegas, Nevada, United States, 89135
      • Alliance for Childhood Diseases ( Site 0064)
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center ( Site 0026)
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Cancer Institute of New Jersey ( Site 0027)
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute ( Site 0040)
    • New Hyde Park, New York, United States, 11040
      • Cohen Children's Medical Center of New York ( Site 0052)
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center ( Site 0060)
    • New York, New York, United States, 10032
      • Columbia University/Herbert Irving Cancer Center ( Site 0063)
    • New York, New York, United States, 10065
      • Weill Cornell Medicine ( Site 0032)
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • UNC Lineberger Comprehensive Cancer ( Site 0044)
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center ( Site 0035)
    • Columbus, Ohio, United States, 43205-2696
      • Nationwide Children's Hospital ( Site 0037)
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • St. Francis Hospital Cancer Center ( Site 0001)
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center-Ingram Cancer Center ( Site 0054)
  • Texas
    • Austin, Texas, United States, 78723
      • Dell Children's Medical Center Of Central Texas ( Site 0058)
    • Dallas, Texas, United States, 75235
      • Children's Medical Center ( Site 0030)
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital ( Site 0042)
    • San Antonio, Texas, United States, 78229
      • Methodist HealthCare System of San Antonio Clinical Trials Office, Texas Transplant Institute ( Site
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital ( Site 0031)
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Childrens Hospital ( Site 0022)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Group 1: Must have newly diagnosed, pathologically confirmed classical Hodgkin Lymphoma (cHL) at Stages IA, IB and IIA without bulky disease. Group 2: Must have newly diagnosed, pathologically confirmed cHL at Stages IIEB, IIIEA,IIIEB, IIIB, IVA and IVB
• Has measurable disease per investigator assessment.
• Male participants are eligible to participate if they agree to the following during the intervention period: refrain from donating sperm plus either be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent or must agree to use contraception per protocol unless confirmed to be azoospermic.
• Female participants who are not pregnant or breastfeeding, and who are either not a woman of childbearing potential (WOCBP), or are a WOCBP who agrees to use approved contraception during the intervention period and for at least 120 days after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period.
• Performance status: Lansky Play-Performance Scale ≥50 for children up to 16 years of age OR Karnofsky score ≥50 for participants ≥ 16 years of age
• Has adequate organ function

Exclusion Criteria:

• Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic stem cell transplantation within the last 5 years
• WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study treatment
• Baseline left ventricular ejection fraction value <50% or shortening fraction of <27%
• Has received prior therapy with an anti-Programmed Death (PD)-1, anti-Programmed Death-Ligand 1 (PD-L1), or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor or has previously participated in a MSD pembrolizumab (MK-3475) clinical study
• Has received any prior systemic anti-cancer therapy,including investigational agents for current diagnosis before randomization
• Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed
• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
• Has a diagnosis of lymphocyte-predominant Hodgkin Lymphoma (HL)
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab
• Has a known additional malignancy that is progressing or requires active treatment within the past 3 years
• Has radiographically detectable central nervous system metastases and/or carcinomatous meningitis as assessed by local site investigator at the time of diagnosis
• Has severe hypersensitivity (≥Grade 3) to any study therapies including any excipients
• An active autoimmune disease that has required systemic treatment in past 2 years
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has an active infection requiring systemic therapy
• Has a known history of human immunodeficiency virus (HIV) infection
• Has a known history of Hepatitis B or known active Hepatitis C virus infection
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study
• Participants who have not adequately recovered from major surgery or have ongoing surgical complications

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembrolizumab + AVD (Group 1); After receiving two 4-week cycles of ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) induction therapy, SER participants in Group 1 will receive pembrolizumab 2 mg/kg up to a maximum of 200 mg (3 to 17 years of age) or 200 mg (18 to 25 years of age) on Day 1 of each 3-week cycle (Q3W) in combination with two cycles of AVD chemotherapy (doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2 and dacarbazine 375 mg/m^2 on Days 1 and 15; cycle frequency every 4 weeks [Q4W]). All SERs in Group 1 will receive radiotherapy (RT) after completing AVD chemotherapy.	Biological: pembrolizumab; 2 mg/kg intravenous (IV) up to a max of 200 mg (3 to 17 years of age) or 200 mg IV (18 to 25 years of age); cycle frequency Q3W; Other Names: MK-3475; Drug: doxorubicin; 25 mg/m^2 IV on Days 1 and 15 as part of ABVD induction therapy (cycle frequency: Q4W, Group 1) 40 mg/m^2 IV on Days 1 and 15 as part of OEPA induction therapy (cycle frequency: Q4W, Group 2) 25 mg/m^2 IV on Days 1 and 15 as part of AVD chemotherapy (cycle frequency: Q4W, Group 1); Drug: vinblastine; 6 mg/m^2 IV on Days 1 and 15 as part of ABVD induction therapy (cycle frequency: Q4W, Group 1) 6 mg/m^2 IV on Days 1 and 15 as part of AVD chemotherapy (cycle frequency: Q4W, Group 1); Drug: dacarbazine; 375 mg/m^2 IV on Days 1 and 15 as part of ABVD induction therapy (cycle frequency: Q4W, Group 1) 375 mg/m^2 IV on Days 1 and 15 as part of AVD chemotherapy (cycle frequency: Q4W, Group 1) 250 mg/m^2 IV on Days 1 to 3 as part of COPDAC-28 chemotherapy (cycle frequency: Q4W, Group 2); Drug: bleomycin; 10 units/m^2 IV on Days 1 and 15 as part of ABVD induction therapy (cycle frequency: Q4W, Group 1); Radiation: Radiotherapy (RT); RT administered daily, dose dependent on randomization group and disease response.
Experimental: Pembrolizumab + COPDAC-28 (Group 2); After receiving two 4-week cycles of OEPA (vincristine, etoposide/etopophos, prednisone/prednisolone and doxorubicin) induction therapy, SER participants in Group 2 will receive pembrolizumab 2 mg/kg up to a maximum of 200 mg (3 to 17 years of age) or 200 mg (18 to 25 years of age) Q3W, in combination with 4 cycles of COPDAC-28 chemotherapy (cyclophosphamide 500 mg/m^2 on Days 1 and 8, vincristine 1.5 mg/m^2 with maximum single dose 2 mg on Days 1 and 8, prednisone/prednisolone 40 mg/m^2/day divided in 3 doses on Days 1 to 15, dacarbazine 250 mg/m^2 on Days 1 to 3; cycle frequency Q4W). SERs in Group 2 will receive RT if they have a positive Positron Emission Tomography (PET) response after completing COPDAC-28 chemotherapy.	Biological: pembrolizumab; 2 mg/kg intravenous (IV) up to a max of 200 mg (3 to 17 years of age) or 200 mg IV (18 to 25 years of age); cycle frequency Q3W; Other Names: MK-3475; Drug: doxorubicin; 25 mg/m^2 IV on Days 1 and 15 as part of ABVD induction therapy (cycle frequency: Q4W, Group 1) 40 mg/m^2 IV on Days 1 and 15 as part of OEPA induction therapy (cycle frequency: Q4W, Group 2) 25 mg/m^2 IV on Days 1 and 15 as part of AVD chemotherapy (cycle frequency: Q4W, Group 1); Drug: dacarbazine; 375 mg/m^2 IV on Days 1 and 15 as part of ABVD induction therapy (cycle frequency: Q4W, Group 1) 375 mg/m^2 IV on Days 1 and 15 as part of AVD chemotherapy (cycle frequency: Q4W, Group 1) 250 mg/m^2 IV on Days 1 to 3 as part of COPDAC-28 chemotherapy (cycle frequency: Q4W, Group 2); Radiation: Radiotherapy (RT); RT administered daily, dose dependent on randomization group and disease response.; Drug: cyclophosphamide; 500 mg/m^2 IV on days 1 and 8 as part of COPDAC-28 chemotherapy (cycle frequency: Q4W, Group 2); Drug: vincristine; 1.5 mg/m^2 IV with maximum single dose 2 mg on Days 1, 8, and 15 as part of OEPA induction therapy (cycle frequency: Q4W, Group 2) 1.5 mg/m^2 IV with maximum single dose 2 mg on Days 1 and 8 as part of COPDAC-28 chemotherapy (cycle frequency: Q4W, Group 2); Drug: prednisone/prednisolone; 60 mg/m^2/day orally divided in 3 doses on Days 1 to 15 as part of OEPA induction therapy (cycle frequency: Q4W, Group 2) 40 mg/m^2/day orally divided in 3 doses on Days 1 to 15 as part of COPDAC-28 chemotherapy (cycle frequency: Q4W, Group 2); Drug: etoposide; 125 mg/m^2 IV on Days 1 to 5 as part of OEPA induction therapy (cycle frequency: Q4W, Group 2); Other Names: Etoposide Phosphate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) in SER Participants By Risk Group (Low, High) as Assessed by Blinded Independent Central Review (BICR)	ORR is defined as the percentage of SER participants who have a Complete Response ([CR], disappearance of all evidence of disease) or Partial Response ([PR], regression of measurable disease and no new sites) using IWG revised response criteria and determined by BICR. The ORR will be estimated by risk group in SER participants.	Up to approximately 8 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Positron Emission Tomography (PET) Scan Negativity in SER Participants By Risk Group (Low, High) After AVD or COPDAC-28 Chemotherapy	The rate of PET negativity for SER participants is the percentage of participants with PET negativity (defined as Deauville score 1, 2 or 3) after two cycles of AVD (Group 1) or four cycles of COPDAC-28 (Group 2), in combination with pembrolizumab. The Deauville 5-point scoring system is an internationally accepted and utilized five-point scoring system for the Fluorodeoxyglucose (FDG) avidity of a Hodgkin's lymphoma or Non-Hodgkin's lymphoma tumor mass as seen on FDG PET scan: Score 1= No uptake above the background, Score 2= Uptake ≤ mediastinum, Score 3= Uptake > mediastinum but ≤ liver, Score 4= Uptake moderately increased compared to the liver at any site, Score 5= Uptake markedly increased compared to the liver at any site or new lesions, Score X= New areas of uptake unlikely to be related to lymphoma. In the present study, scores of 1, 2 and 3 are considered to be negative and scores of 4 and 5 are considered to be positive.	Up to approximately 8 years
Event-Free Survival (EFS) in SER Participants By Risk Group (Low, High) as Assessed by BICR	EFS is defined as the time from study enrollment to the first documented disease progression or recurrence, or death due to any cause, whichever occurs first. Progression/disease recurrence will be determined by BICR using IWG criteria.	Up to approximately 8 years
Overall Survival (OS) in SER Participants By Risk Group (Low, High)	OS is defined as the time from study enrollment to death due to any cause. Participants without documented death will be censored at the date of the last follow-up.	Up to approximately 8 years
Exposure to Radiotherapy (RT) in SER Participants By Risk Group (Low, High)	The frequency of RT received by eligible participants (positive PET response, i.e. Deauville score of 4 or 5) will be reported.	Up to approximately 8 years
Rate of PET Scan Negativity In Group 1 Participants After ABVD Induction Therapy	The rate of PET negativity for Group 1 participants is the percentage of participants with PET negativity (defined as Deauville score 1, 2 or 3) after two cycles of ABVD induction as per investigator assessment. The Deauville 5-point scoring system is an internationally accepted and utilized five-point scoring system for the FDG avidity of a Hodgkin's lymphoma or Non-Hodgkin's lymphoma tumor mass as seen on FDG PET scan: Score 1= No uptake above the background, Score 2= Uptake ≤ mediastinum, Score 3= Uptake > mediastinum but ≤ liver, Score 4= Uptake moderately increased compared to the liver at any site, Score 5= Uptake markedly increased compared to the liver at any site or new lesions, Score X= New areas of uptake unlikely to be related to lymphoma. In the present study, scores of 1, 2 and 3 are considered to be negative and scores of 4 and 5 are considered to be positive.	Up to approximately 8 years
EFS in Rapid Early Responder (RER) Participants By Risk Group (Low, High) as Assessed by Investigator	EFS is defined as the time from study enrollment to the first documented disease progression or recurrence, or death due to any cause, whichever occurs first. Progression/disease recurrence will be determined by the investigator.	Up to approximately 8 years
OS in RER Participants By Risk Group (Low, High)	OS is defined as the time from study enrollment to death due to any cause. Participants without documented death will be censored at the date of the last follow-up.	Up to approximately 8 years
Serum Thymus and Activation-Regulated Chemokine (TARC) Levels in SER Participants By Risk Group (Low, High)	Serum TARC levels will be measured and evaluated as a potential biomarker in SER participants by risk group at screening, early, and late response assessments.	Up to approximately 8 years
Number of SER Participants Experiencing an Adverse Event (AE) By Risk Group (Low, High)	An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. 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 treatment. The number of SER participants who experience an AE will be reported for each arm.	Up to approximately 8 years
Number of SER Participants Discontinuing Study Treatment Due to AEs By Risk Group (Low, High)	An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. 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 treatment. The number of SER participants who discontinue study treatment due to an AE will be reported for each arm.	Up to approximately 8 years

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): April 9, 2018
• Primary Completion (Estimated): February 13, 2027
• Study Completion (Estimated): February 13, 2027

Study Registration Dates

• First Submitted: January 17, 2018
• First Submitted That Met QC Criteria: January 17, 2018
• First Posted (Actual): January 23, 2018

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: PD1; PDL1; Programmed Death-Ligand 1 (PD-L1); Programmed Death-1 (PD-1)
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Immune Checkpoint Inhibitors; Prednisolone; Cyclophosphamide; Etoposide; Etoposide phosphate; Pembrolizumab; Prednisone; Doxorubicin; Vincristine; Dacarbazine; Bleomycin; Vinblastine
• Other Study ID Numbers: 3475-667; MK-3475-667 (Other Identifier: Merck Protocol Number); 2017-001123-53 (EudraCT Number); 2023-504821-38 (Registry Identifier: EU CT)

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