Clinical trial NCT04317066: A Study of Pembrolizumab (MK-3475) in Participants With Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) (MK-3475-A33/KEYNOTE-A33)
Official title: A Phase 1 Clinical Study of Pembrolizumab (MK-3475) in Participants With Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) (KEYNOTE-A33)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma, B-Cell
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2020-03-20
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Objective Response Rate (ORR) Using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma as Assessed by Independent Central Review
timeFrame: Up to approximately 24 months
measure: Number of Participants Who Experienced at Least One Adverse Event (AE)
timeFrame: Up to approximately 27 months
measure: Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Objective Response Rate (ORR) Using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma as Assessed by Investigator
timeFrame: Up to approximately 24 months
measure: Disease Control Rate (DCR) Using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma as Assessed by Independent Central Review
timeFrame: Up to approximately 24 months
measure: Disease Control Rate (DCR) Using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma as Assessed by Investigator
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Nagoya University Hospital ( Site 0002)
state: Aichi
city: Sapporo
country: Japan
facility: Hokkaido University Hospital ( Site 0006)
state: Hokkaido
city: Osakasayama
country: Japan
facility: Kindai University Hospital ( Site 0001)
state: Osaka
city: Tachikawa
country: Japan
facility: National Hospital Organization Disaster Medical Center ( Site 0007)
state: Tokyo
city: Fukuoka
country: Japan
facility: Kyushu University Hospital ( Site 0008)
city: Okayama
country: Japan
facility: Okayama University Hospital ( Site 0004)
city: Tokyo
country: Japan
facility: National Cancer Center Hospital ( Site 0005)
city: Tokyo
country: Japan
facility: Tokyo Metropolitan Komagome Hospital ( Site 0009)
city: Yamagata
country: Japan
facility: Yamagata University Hospital ( Site 0003)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.