A Study of Pembrolizumab (MK-3475) in Relapsed or Refractory Classical Hodgkin's Lymphoma (rrcHL) or Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) (MK-3475-B68)

A Phase 2 Study of Pembrolizumab (MK-3475) Every 6 Weeks (Q6W) in Participants With Relapsed or Refractory Classical Hodgkin's Lymphoma (rrcHL) or Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL)

The primary objective of the study is to evaluate the objective response rate (ORR), by cohort, rrcHL and rrPMBCL, as assessed by the investigator according to Lugano classification criteria 2014 in participants treated with pembrolizumab Q6W.

Study Overview

• Status: Active, not recruiting
• Conditions: Hodgkin's Lymphoma; Primary Mediastinal Large B-cell Lymphoma (PMBCL)
• Intervention / Treatment: Biological: Pembrolizumab

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Parana
    • Curitiba, Parana, Brazil, 81520-060
      • Hospital Erasto Gaertner ( Site 1703)
  • Sao Paulo
    • Barretos, Sao Paulo, Brazil, 14784-400
      • Fundação Pio XII - Hospital de Câncer de Barretos ( Site 1701)
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute ( Site 0207)
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove-IV. interni hematologicka klinika ( Site 0304)
  • Brno-mesto
    • Brno, Brno-mesto, Czechia, 625 00
      • Fakultni nemocnice Brno Bohunice-Interni hematologicka a onkologicka klinika ( Site 0302)
  • Praha 10
    • Prague, Praha 10, Czechia, 100 34
      • Fakultni nemocnice Kralovske Vinohrady-Interni hematologicka klinika ( Site 0303)
• France
  • Cote-d Or
    • Dijon, Cote-d Or, France, 21000
      • Centre Hospitalier Universitaire Dijon Bourgogne - Hôpital François Mitterrand ( Site 0401)
  • Ile-de-France
    • Villejuif, Ile-de-France, France, 94800
      • Gustave Roussy ( Site 0402)
• Italy
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0503)
  • Lombardia
    • Pavia, Lombardia, Italy, 27100
      • Fondazione IRCCS Policlinico San Matteo ( Site 0509)
  • Sicilia
    • Palermo, Sicilia, Italy, 90146
      • Az. Osp. Ospedali Riuniti VILLA SOFIA-CERVELLO-EMATOLOGIA I ( Site 0507)
• Poland
  • Malopolskie
    • Krakow, Malopolskie, Poland, 30-510
      • Pratia MCM Krakow ( Site 0064)
  • Pomorskie
    • Gdańsk, Pomorskie, Poland, 80-952
      • Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 0063)
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland, 61-848
      • Szpital Kliniczny im. Przemienienia Panskiego Uniwersytetu M-Oddzial Hematologii i Transplantacji S
• Russian Federation
  • Moskva
    • Moscow, Moskva, Russian Federation, 105203
      • The National Medico-Surgical Center N.I. Pirogov ( Site 0801)
    • Moscow, Moskva, Russian Federation, 125284
      • Moscow City Clinical Hospital S.P. Botkin ( Site 0803)
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 197341
      • Almazov National Medical Research Centre ( Site 0807)
• South Africa
  • Gauteng
    • Centurion, Gauteng, South Africa, 0044
      • Netcare Pretoria East Hospital-Albert Alberts Stem Cell Transplant Centre ( Site 0902)
    • Johannesburg, Gauteng, South Africa, 1864
      • Wits Clinical Research ( Site 0904)
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7925
      • Groote Schuur Hospital ( Site 0906)
• Turkey
  • Ankara, Turkey, 06100
    • Ankara University Department of Hematology, Clinical Research Unit ( Site 1101)
  • Izmir
    • Bornova, Izmir, Turkey, 35100
      • Ege University Medicine of Faculty ( Site 1105)
• Ukraine
  • Kharkivska Oblast
    • Kharkiv, Kharkivska Oblast, Ukraine, 61070
      • CNPE Regional Center of Oncology ( Site 1305)
  • Kyivska Oblast
    • Kyiv, Kyivska Oblast, Ukraine, 03022
      • National Cancer Institute ( Site 1303)
• United States
  • California
    • Torrance, California, United States, 90502
      • Lundquist Institute for Biomedical Innovation at Harbor-UCLA-Hematology and Medical Oncology ( Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane Medical Center ( Site 0110)
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Anne Arundel Medical Center-Anne Arundel Oncology and Hematology ( Site 0125)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Have a histologically confirmed diagnosis of cHL or PMBCL, according to the World Health Organization (WHO) classification [Swerdlow, S. H., et al 2008].
• Has radiographically measurable cHL or PMBCL disease as per Lugano classification with at least 1 nodal lesion (which has not been previously radiated) that is >15 mm in long axis, regardless of the length of the short axis, and/or extranodal lesion of >10 mm in long and short axis.

PMBCL-Specific Disease Characteristics:

• Have relapsed or refractory PMBCL and:
• Have relapsed after auto-stem cell transplant (SCT) or have failed to achieve a CR or PR within 60 days of auto-SCT. Participants may have received intervening therapy after auto-SCT for relapsed or refractory disease, in which case they must have relapsed after or be refractory to their last treatment.

OR

- For participants who are ineligible for auto-SCT, have received at least ≥2 lines of prior therapy and have failed to respond to or relapsed after their last line of treatment. At least 1 of the prior lines of therapy must contain a rituximab-based regimen.

Note: Participants should not need urgent cytoreductive therapy.

• Relapsed Disease: disease progression after achieving an overall response of PR or CR in response to the most recent therapy
• Refractory Disease: failure to achieve CR or PR to the most recent therapy.

cHL-Specific Disease Characteristics:

• Have relapsed or refractory cHL and:
• Have relapsed during their last cHL regimen after receiving at least 2 cycles of therapy or within 12 months after completing the last regimen for cHL.

OR

• Have received at least ≥1 line of prior multiagent therapy with/without brentuximab vedotin (excluding radiation) or auto-SCT for cHL and have failed to respond to or relapsed after their last line of treatment.

  • Relapsed Disease: disease progression after achieving an overall response of PR or CR to the most recent therapy.
  • Refractory Disease: failure to achieve CR or PR to the most recent therapy.
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
• Is not a woman of child bearing potential (WOCBP). OR
• Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), for at least 120 days after the last dose of study intervention.
• Submit an evaluable core lymph node biopsy for biomarker analysis from an archival (>60 days) or newly obtained (within 30 days) core or incisional biopsy at Screening which was not previously irradiated. Note: If no archival tissue is available, 2 new fresh core needle samples are required.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Life expectancy >3 months.
• Adequate organ function.

Exclusion Criteria:

• Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic SCT within the last 5 years
• Has clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class ≥II), or serious cardiac arrhythmia requiring medication
• Has pericardial effusion or clinically significant pleural effusion
• Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in situ cancers
• Is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) <3 days prior to the first dose of study intervention. Note: Participants who receive daily steroid replacement therapy are an exception
• Has received prior monoclonal antibody within 4 weeks prior to first dose of study intervention or has not recovered (i.e., ≤Grade 1 or at baseline) from adverse event (AEs) due to agents administered more than 4 weeks earlier
• Has received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti-programmed cell death ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137)
• Has received prior chimeric antigen receptor T-cell (CAR-T) therapy
• Has received prior systemic anticancer therapy, or radiotherapy, including investigational agents within 4 weeks prior to the first dose of study intervention. Note: If the participant had a major operation, the participant must have recovered adequately from the procedure and/or any complications from the operation before starting study intervention
• Has received prior radiotherapy within 2 weeks of start of study intervention or have had a history of radiation pneumonitis. Participants must have recovered from all radiation-related toxicities, and not require corticosteroids
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study drug
• 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 (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
• Has known active central nervous system (CNS) lymphoma involvement or active CNS involvement by lymphoma
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
• Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
• Has a history of (noninfectious) 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. No HIV testing is required unless mandated by local health authority
• Has a known history of Hepatitis B (defined as hepatitis B surface antigen (HBsAg) reactive) or known active Hepatitis C virus infection

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Pembrolizumab (MK-3475), 400 mg, Q6W, intravenous (IV) infusion, Day 1 then Q6W up to 18 doses.	Biological: Pembrolizumab; Pembrolizumab, 400 mg, Q6W, intravenous (IV) infusion.; Other Names: MK-3475; SCH 900475; KEYTRUDA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) per Lugano Classification as Assessed by Investigator	ORR is defined as the percentage of the participants who had complete response (CR) or partial response (PR) and will be evaluated using computed tomography (CT) and metabolic imaging (fluorodeoxyglucose- positron emission tomography (FDG-PET)), and clinical information. CR is complete metabolic (no/minimal FDG uptake) and radiologic response (target lesions regress to ≤5 cm in longest transverse diameter of a lesion) and no new lesions. PR is partial metabolic (moderate/high FDG uptake) and radiologic response (≥50% decrease in sum of product diameters for multiple lesions of up to 6 target measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by >50% in length beyond normal). The percentage of participants treated with pembrolizumab Q6W, by cohort, rrcHL and rrPMBCL, who experience CR or PR as assessed by investigator will be presented.	Up to approximately 40 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR) per Lugano Classification as Assessed by Investigator	For participants who demonstrate a CR or PR, 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. Participants will be evaluated using CT and metabolic imaging (FDG-PET), and clinical information. CR is complete metabolic (no/minimal FDG uptake) and radiologic response (target lesions regress to ≤5 cm in longest transverse diameter of a lesion) and no new lesions. PR is partial metabolic (moderate/high FDG uptake) and radiologic response (≥50% decrease in sum of product diameters for multiple lesions of up to 6 target measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by >50% in length beyond normal). DOR as assessed by investigator will be presented among participants who demonstrated CR or PR on treatment with pembrolizumab Q6W, by cohort, rrcHL and rrPMBCL.	Up to approximately 40 months
Area Under the Curve (AUC) of Pembrolizumab	Area under the plasma-time curve.	Predose 0-4 hours on Cycle1 Day1, Cycle2 Day1, Cycle4 Day1, Cycle5 Day1, Cycle7 Day1, Cycle9 Day1, Cycle13 Day1, Cycle17 Day1 and end of infusion on Cycle1 Day1, Cycle4 Day1 and anytime on Cycle1 Day22 and Cycle4 Day22 (cycle length = 6 weeks)
Maximum Serum Concentration (Cmax) of Pembrolizumab	Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.	Predose 0-4 hours on Cycle1 Day1, Cycle2 Day1, Cycle4 Day1, Cycle5 Day1, Cycle7 Day1, Cycle9 Day1, Cycle13 Day1, Cycle17 Day1 and end of infusion on Cycle1 Day1, Cycle4 Day1 and anytime on Cycle1 Day22 and Cycle4 Day22 (cycle length = 6 weeks)
Minimum Serum Concentration (Cmin) of Pembrolizumab	Cmin is a measure of the minimum amount of drug in the plasma after the dose is given.	Predose 0-4 hours on Cycle1 Day1, Cycle2 Day1, Cycle4 Day1, Cycle5 Day1, Cycle7 Day1, Cycle9 Day1, Cycle13 Day1, Cycle17 Day1 and end of infusion on Cycle1 Day1, Cycle4 Day1 and anytime on Cycle1 Day22 and Cycle4 Day22 (cycle length = 6 weeks)
Antidrug Antibody Levels (ADA) for Pembrolizumab	ADA response to pembrolizumab at the beginning of each of the first 5 cycles will be determined.	Predose 0-4 hours on Cycle1 Day1, Cycle2 Day1, Cycle4 Day1, Cycle5 Day1, Cycle7 Day1, Cycle9 Day1, Cycle13 Day1, Cycle17 Day1 and end of infusion on Cycle1 Day1, Cycle4 Day1 and anytime on Cycle1 Day22 and Cycle4 Day22 (cycle length = 6 weeks)
Number of Participants Who Experienced an Adverse Event (AE)	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to approximately 30 months
Number of Participants Who Discontinued Study Treatment Due to AE	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to approximately 27 months
Objective Response Rate (ORR) per Lugano Classification as Assessed by Blinded Independent Central Review (BICR)	ORR is defined as the percentage of the participants who had complete response (CR) or partial response (PR) and will be evaluated using computed tomography (CT) and metabolic imaging (fluorodeoxyglucose- positron emission tomography (FDG-PET)), and clinical information. CR is complete metabolic (no/minimal FDG uptake) and radiologic response (target lesions regress to ≤5 cm in longest transverse diameter of a lesion) and no new lesions. PR is partial metabolic (moderate/high FDG uptake) and radiologic response (≥50% decrease in sum of product diameters for multiple lesions of up to 6 target measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by >50% in length beyond normal). The percentage of participants treated with pembrolizumab Q6W, by cohort, rrcHL and rrPMBCL, who experience CR or PR as assessed by BICR will be presented.	Up to approximately 40 months
Duration of Response (DOR) per Lugano Classification as Assessed by BICR	For participants who demonstrate a CR or PR, 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. Participants will be evaluated using CT and metabolic imaging (FDG-PET), and clinical information. CR is complete metabolic (no/minimal FDG uptake) and radiologic response (target lesions regress to ≤5 cm in longest transverse diameter of a lesion) and no new lesions. PR is partial metabolic (moderate/high FDG uptake) and radiologic response (≥50% decrease in sum of product diameters for multiple lesions of up to 6 target measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by >50% in length beyond normal). DOR as assessed by BICR will be presented among participants who demonstrated CR or PR on treatment with pembrolizumab Q6W, by cohort, rrcHL and rrPMBCL.	Up to approximately 40 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

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2021
• Primary Completion (Actual): December 14, 2023
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: April 27, 2021
• First Submitted That Met QC Criteria: May 4, 2021
• First Posted (Actual): May 6, 2021

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: PD-1; PD-L1; PD1; PDL1
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Hodgkin Disease; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: 3475-B68; MK-3475-B68 (Other Identifier: Merck); 2020-005609-20 (EudraCT Number)

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