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)

NCT04875195 | Completed Phase 2 Results FDA Drug

• 5 other identifiers: 3475-B68MK-3475-B682024-510979-38-00U1111-1302-86342020-005609-20
• Study Type: interventional
• Target: 66
• Locations: 11 countries
• Sites: 27

Brief Summary

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 every six weeks (Q6W).

Conditions

Hodgkin's Lymphoma; Primary Mediastinal Large B-cell Lymphoma (PMBCL)

Keywords

PD1; PD-1; PDL1; PD-L1

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) Per Lugano Classification as Assessed by Investigator

  ORR was defined as the percentage of the participants who had complete response (CR) or partial response (PR) and was evaluated using computed tomography (CT) and metabolic imaging (fluorodeoxyglucose- positron emission tomography (FDG-PET)). CR is 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. 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 experienced CR or PR as assessed by investigator is presented.

  Up to approximately 30 months

Secondary Outcomes (12)

• ORR Per Lugano Classification as Assessed by Blinded Independent Central Review (BICR)

  Up to approximately 30 months

• Duration of Response (DOR) Per Lugano Classification as Assessed by Investigator

  Up to approximately 54 months

• DOR Per Lugano Classification as Assessed by BICR

  Up to approximately 54 months

• Area Under the Curve (AUC) Early Cycle of Pembrolizumab

  Predose on Day 1 and Day 42 of Cycle 1 (cycle length=6 weeks)

• Area Under the Curve (AUC) Steady State of Pembrolizumab

  Predose on Day 1 and Day 42 of Cycle 4 (cycle length=6 weeks)

Study Arms (1)

Arm 1

EXPERIMENTAL

Pembrolizumab (MK-3475), 400 mg, Q6W, intravenous (IV) infusion, Day 1 then Q6W up to 18 doses.

Biological: Pembrolizumab

Interventions

Pembrolizumab BIOLOGICAL

Pembrolizumab, 400 mg, Q6W, intravenous (IV) infusion.

Also known as: MK-3475, SCH 900475, KEYTRUDA®

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• \- 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.
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (27)

Lundquist Institute for Biomedical Innovation at Harbor-UCLA-Hematology and Medical Oncology ( Site

Torrance, California, 90502, United States

Location

Tulane Medical Center ( Site 0110)

New Orleans, Louisiana, 70112, United States

Location

Anne Arundel Medical Center-Anne Arundel Oncology and Hematology ( Site 0125)

Annapolis, Maryland, 21401, United States

Location

Hospital Erasto Gaertner ( Site 1703)

Curitiba, Paraná, 81520-060, Brazil

Location

Fundação Pio XII - Hospital de Câncer de Barretos ( Site 1701)

Barretos, São Paulo, 14784-400, Brazil

Location

Cross Cancer Institute ( Site 0207)

Edmonton, Alberta, T6G 1Z2, Canada

Location

Fakultni nemocnice Brno Bohunice-Interni hematologicka a onkologicka klinika ( Site 0302)

Brno, Brno-mesto, 625 00, Czechia

Location

Fakultni nemocnice Kralovske Vinohrady-Interni hematologicka klinika ( Site 0303)

Prague, Praha 10, 100 34, Czechia

Location

Fakultni nemocnice Hradec Kralove-IV. interni hematologicka klinika ( Site 0304)

Hradec Králové, 500 05, Czechia

Location

Centre Hospitalier Universitaire Dijon Bourgogne - Hôpital François Mitterrand ( Site 0401)

Dijon, Cote-d Or, 21000, France

Location

Gustave Roussy ( Site 0402)

Villejuif, Île-de-France Region, 94800, France

Location

Fondazione IRCCS Policlinico San Matteo ( Site 0509)

Pavia, Lombardy, 27100, Italy

Location

Az. Osp. Ospedali Riuniti VILLA SOFIA-CERVELLO-EMATOLOGIA I ( Site 0507)

Palermo, Sicily, 90146, Italy

Location

Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0503)

Napoli, 80131, Italy

Location

Szpital Kliniczny im. Przemienienia Panskiego Uniwersytetu M-Oddzial Hematologii i Transplantacji S

Poznan, Greater Poland Voivodeship, 61-848, Poland

Location

Pratia MCM Krakow ( Site 0064)

Krakow, Lesser Poland Voivodeship, 30-510, Poland

Location

Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 0063)

Gdansk, Pomeranian Voivodeship, 80-952, Poland

Location

The National Medico-Surgical Center N.I. Pirogov ( Site 0801)

Moscow, Moscow, 105203, Russia

Location

Moscow City Clinical Hospital S.P. Botkin ( Site 0803)

Moscow, Moscow, 125284, Russia

Location

Almazov National Medical Research Centre ( Site 0807)

Saint Petersburg, Sankt-Peterburg, 197341, Russia

Location

Netcare Pretoria East Hospital-Albert Alberts Stem Cell Transplant Centre ( Site 0902)

Centurion, Gauteng, 0044, South Africa

Location

Wits Clinical Research ( Site 0904)

Johannesburg, Gauteng, 1864, South Africa

Location

Groote Schuur Hospital ( Site 0906)

Cape Town, Western Cape, 7925, South Africa

Location

Ege University Medicine of Faculty ( Site 1105)

Bornova, İzmir, 35100, Turkey (Türkiye)

Location

Ankara University Department of Hematology, Clinical Research Unit ( Site 1101)

Ankara, 06100, Turkey (Türkiye)

Location

CNPE Regional Center of Oncology ( Site 1305)

Kharkiv, Kharkivs’ka Oblast’, 61070, Ukraine

Location

National Cancer Institute ( Site 1303)

Kyiv, Kyivska Oblast, 03022, Ukraine

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Hodgkin Disease

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

clinicaltrialsdisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2021
• First Posted: May 6, 2021
• Study Start: June 7, 2021
• Primary Completion: December 14, 2023
• Study Completion: October 13, 2025
• Last Updated: October 29, 2025
• Results First Posted: February 10, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

UA (2); CA (1); CZ (3); FR (2); ZA (3); IT (3); RU (3); TU (2); PL (3); BR (2); US (3)