A Study of Pembrolizumab (MK-3475) in Participants With Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) (MK-3475-A33/KEYNOTE-A33)

A Phase 1 Clinical Study of Pembrolizumab (MK-3475) in Participants With Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) (KEYNOTE-A33)

The purpose of this study is to evaluate the objective response, safety, and tolerability of pembrolizumab in Japanese participants who have refractory primary mediastinal large B-cell lymphoma.

Study Overview

• Status: Active, not recruiting
• Conditions: Lymphoma, B-Cell
• Intervention / Treatment: Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Estimated): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital ( Site 0008)
  • Okayama, Japan, 700-8558
    • Okayama University Hospital ( Site 0004)
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital ( Site 0005)
  • Tokyo, Japan, 113-8677
    • Tokyo Metropolitan Komagome Hospital ( Site 0009)
  • Yamagata, Japan, 990-9585
    • Yamagata University Hospital ( Site 0003)
  • Aichi
    • Nagoya, Aichi, Japan, 466-8560
      • Nagoya University Hospital ( Site 0002)
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital ( Site 0006)
  • Osaka
    • Osakasayama, Osaka, Japan, 589-8511
      • Kindai University Hospital ( Site 0001)
  • Tokyo
    • Tachikawa, Tokyo, Japan, 190-0014
      • National Hospital Organization Disaster Medical Center ( Site 0007)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosis of Primary mediastinal B-cell lymphoma (PMBCL)

• Relapsed or refractory PMBCL and:

  • Relapsed after auto-stem cell transplantation (SCT) or have failed to achieve a CR or PR within 60 days of auto-SCT; or
  • For participants who are ineligible for auto-SCT, has received at least ≥ 2 lines of prior therapy and have failed to respond to or relapsed after their last line of treatment. For participants who received consolidative local radiotherapy after systemic therapy, local radiotherapy will not be considered as a separate line of treatment.
• Previously exposed to rituximab as part of prior lines of treatment.
• Radiographically measurable disease
• Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Life expectancy ≥3 months.
• Adequate organ function.
• Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study drug through 120 days after the last dose of study drug, OR must be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent.
• Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug, OR must be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent.

Exclusion Criteria:

• Received prior therapy with an anti-PD-1 (programmed cell death protein 1), anti-PD-L1 (programmed death-ligand 1), or anti-PD-L2 (programmed cell death 1 ligand 2), or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4 [cytotoxic T-lymphocyte-associated protein 4], OX 40, or CD137 [cluster of differentiation 137])
• Received chimeric antigen receptor (CAR) T-cell therapy.
• Prior monoclonal antibody or radiation therapy within 4 weeks prior to the first dose of study intervention; OR received prior chemotherapy or targeted small molecule therapy within 2 weeks prior to the first dose of study intervention; OR has not recovered from adverse events due to a previously administered agent above. Participants with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Major surgery within 3 weeks prior to first dose of study intervention.
• Received a live vaccine within 30 days prior to the first dose of study drug.
• Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention. Participants in the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• 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 drug.
• Known additional malignancy that is progressing or has required active treatment within the past 3 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, that have undergone potentially curative therapy.
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Active autoimmune disease that has required systemic treatment in past 2 years
• History of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
• Active infection requiring systemic therapy.
• History of human immunodeficiency virus (HIV) or Hepatitis B.
• Active Hepatitis C virus infection.
• Known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
• Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention.
• Allogeneic hematopoietic stem cell/solid organ transplantation within the last 5 years.

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: Pembrolizumab in Participants with rrPMBCL; Participants with relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL) receive pembrolizumab 200 mg by intravenous (IV) infusion every 3 weeks (Q3W) for up to 24 months.	Drug: Pembrolizumab; Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.; Other Names: MK-3475; KEYTRUDA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) as Assessed by Independent Central Review	ORR is defined as the percentage of participants who have a Complete Response (CR) or Partial Response (PR). The percentage of participants who experience a CR or PR as assessed by blinded independent central review will be presented.	Up to approximately 3 years
Number of Participants Who Experienced One or More Adverse Events (AEs)	An adverse event (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 3 years
Number of Participants Who Discontinue Study Treatment Due to 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 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) as Assessed by Investigator	ORR is defined as the percentage of participants who have a Complete Response (CR) or Partial Response (PR). The percentage of participants who experience a CR or PR as assessed by investigator review will be presented.	Up to approximately 3 years
Disease Control Rate (DCR) as Assessed by Independent Central Review	DCR is defined as the percentage of participants who have a Complete Response (CR), a Partial Response (PR), or stable disease (SD). The percentage of participants who experience a CR, a PR, or SD as assessed by blinded independent central review will be presented.	Up to approximately 3 years
Disease Control Rate (DCR) as Assessed by Investigator	DCR is defined as the percentage of participants who have a Complete Response (CR), a Partial Response (PR), or stable disease (SD). The percentage of participants who experience a CR, a PR, or SD as assessed by investigator review will be presented.	Up to approximately 3 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

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2020
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): April 30, 2024

Study Registration Dates

• First Submitted: March 19, 2020
• First Submitted That Met QC Criteria: March 19, 2020
• First Posted (Actual): March 20, 2020

Study Record Updates

• Last Update Posted (Estimated): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 18, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1)
• 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; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: 3475-A33; 205262 (Registry Identifier: Japic-CTI); MK-3475-A33 (Other Identifier: Merck); KEYNOTE-A33 (Other Identifier: Merck); 2080225167 (Other Identifier: JRCT)

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: No
• Studies a U.S. FDA-regulated device product: No