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

NCT ID: NCT04317066

Last Updated: 2025-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-26
• Study Completion Date: 2024-04-11

Brief Summary

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.

Conditions

Lymphoma, B-Cell

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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 on day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years).

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab 200 mg by intravenous (IV) infusion, given on day 1 of each 3-week cycle.

Interventions

Pembrolizumab

Pembrolizumab 200 mg by intravenous (IV) infusion, given on day 1 of each 3-week cycle.

Intervention Type: DRUG

Other Intervention Names

KEYTRUDA®; MK-3475

Eligibility Criteria

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 complete response (CR) or partial response (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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Nagoya University Hospital ( Site 0002)

Nagoya, Aichi-ken, Japan

Hokkaido University Hospital ( Site 0006)

Sapporo, Hokkaido, Japan

Kindai University Hospital ( Site 0001)

Sayama, Osaka, Japan

National Hospital Organization Disaster Medical Center ( Site 0007)

Tachikawa, Tokyo, Japan

Kyushu University Hospital ( Site 0008)

Fukuoka, , Japan

Okayama University Hospital ( Site 0004)

Okayama, , Japan

National Cancer Center Hospital ( Site 0005)

Tokyo, , Japan

Tokyo Metropolitan Komagome Hospital ( Site 0009)

Tokyo, , Japan

Yamagata University Hospital ( Site 0003)

Yamagata, , Japan

Countries

Japan

References

Kato K, Nakamura S, Wakana A, Koh Y, Izutsu K. Pembrolizumab in Japanese patients with primary mediastinal large B-cell lymphoma: results from the KEYNOTE-A33 study. Int J Clin Oncol. 2024 Dec;29(12):1977-1983. doi: 10.1007/s10147-024-02627-8. Epub 2024 Sep 18.

Reference Type: RESULT

PMID: 39294486 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://merckclinicaltrials.com/

Merck Clinical Trials Information

Other Identifiers

MK-3475-A33

Identifier Type: OTHER

Identifier Source: secondary_id

KEYNOTE-A33

Identifier Type: OTHER

Identifier Source: secondary_id

205262

Identifier Type: REGISTRY

Identifier Source: secondary_id

2080225167

Identifier Type: OTHER

Identifier Source: secondary_id

3475-A33

Identifier Type: -

Identifier Source: org_study_id