Nemtabrutinib and Pembrolizumab for the Treatment of Richter Transformation, Diffuse Large B-cell Lymphoma Subtype
2 other identifiers
interventional
32
1 country
1
Brief Summary
This phase II trial tests how well nemtabrutinib in combination with pembrolizumab works in treating patients with Richter transformation, diffuse large B-cell lymphoma subtype (RT-DLBCL). Nemtabrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cells (a type of white blood cell) in cancers such as Richter transformation at abnormal levels. This may help keep cancer cells from growing and spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Giving nemtabrutinib in combination with pembrolizumab may kill more cancer cells in patients with RT-DLBCL.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Apr 2026
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 26, 2025
CompletedFirst Posted
Study publicly available on registry
March 7, 2025
CompletedStudy Start
First participant enrolled
April 15, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 1, 2030
March 24, 2026
March 1, 2026
3 years
February 26, 2025
March 23, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
Overall response rate
Will be defined as having either a complete response (CR) or partial response (PR) as per Cheson et al., 2014. Will be summarized using frequencies and relative frequencies.
After 6 cycles (approximately 18 weeks) (1 cycle = 21 days)
Quality of life
Tolerability and patient-reported outcomes (PROs) assessed using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (version 3) . EORTC-C 30 is measure from nat at all (better) to very much (worse)
Up to 3 years after completion of study treatment
Quality of life -PRO CTCAE
Will be evaluated using the patient reported outcome PRO CTCAE measurement system. Responses are scored on a 0-5 point scale where higher outcomes indicate worse
Up to 3 years after completion of study treatment
Secondary Outcomes (5)
Response outcomes
Up to 3 years after completion of study treatment
Duration of response
From first PR (or greater) until disease progression or last follow-up, assessed up to 3 years after completion of study treatment
Overall survival
From treatment initiation until death due to any cause or last follow-up, assessed up to 3 years after completion of study treatment
Progression-free survival
From treatment initiation until disease progression, death due to any cause, subsequent treatment, or last follow-up, assessed up to 3 years
Incidence of adverse events
Up to 30 days after the last dose of study treatment
Study Arms (1)
Treatment (nemtabrutinib, pembrolizumab)
EXPERIMENTALPatients receive nemtabrutinib PO QD on days 1-21 of each cycle and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 35 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA during screening, PET/CT or CT and blood sample collection throughout the trial. Patients may also undergo bone marrow biopsy throughout the trial.
Interventions
Undergo MUGA
Given IV
Undergo PET/CT
Undergo blood sample collection
Undergo bone marrow biopsy
Undergo PET/CT or CT
Given PO
Eligibility Criteria
You may qualify if:
- Patients with biopsy-proven Richter transformation, diffuse large B-cell lymphoma subtype (RT-DLBCL) from an antecedent or concurrently diagnosed chronic lymphocytic leukemia (CLL) and/or small lymphocytic lymphoma (SLL).
- Be ineligible for frontline anthracycline-based chemoimmunotherapy (determined by treating investigator) OR have clinical evidence of disease progression after any prior treatment for RT-DLBCL.
- Participants who have adverse events (AEs) due to previous anti-cancer therapies must have recovered to ≤ grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤ grade 2 neuropathy are eligible.
- Note: Participants who have lingering cytopenias from prior anti-cancer therapy or progressive disease may be eligible at the discretion of the study principal investigator (PI), provided they meet all other study criteria.
- Have measurable disease as determined by imaging (by positron-emission tomography \[PET\] and/or computed tomography \[CT\] scans), immunohistochemistry, and/or flow cytometry, as per the Cheson criteria.
- Have the ability to swallow and retain oral medication.
- Age 18 years and older on the day of signing informed consent.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Be free from other malignancy within 2 years prior to enrollment (with the exception of CLL/SLL, low-risk and early stage \[T1-T2a- Gleason score ≤ 6, and prostate-specific antigen \[PSA\] \< 10 ng/mL\] prostate cancer, or localized skin cancer that has undergone potentially curative therapy).
- Absolute neutrophil count: ANC ≥ 500 cells/µL (without G-CSF dose within the last 7 days prior to initiation of study treatment
- Platelets: ≥ 25,000/µL -not requiring transfusion within the last 3 days prior to initiation of study treatment). Patients on medications that increase bleeding risk (e.g. systemic anticoagulation, anti-platelet therapies, etc.) must have a platelet count ≥50,000 /µL and have no history of major bleeding.
- Hemoglobin: ≥ 7gm/dL (transfusion support allowed).
- Total bilirubin: ≤ 1.5 x upper limit of normal (ULN) OR direct bilirubin ≤ ULN for participants with total bilirubin levels \> 1.5 x ULN.
- Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic-pyruvic transaminase \[SGPT\]): ≤ 2.5 x ULN (≤ 5 x ULN for participants with liver metastases).
- Creatinine clearance (CrCl): ≥ 30 mL/min (per Cockroft-Gault equation).
- +12 more criteria
You may not qualify if:
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PDL2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX40, CD137).
- Has received prior systemic anti-cancer therapy within 5 half-lives of last dose (or within 30 days for cellular therapy or investigational agents, or within 100 days post allogeneic hematopoietic stem cell transplantation and without any grade ≥ 2 graft versus host disease) prior to enrollment.
- Has received prior radiotherapy within 2 weeks of start of study intervention or has radiation related toxicities requiring corticosteroids. Note: Two weeks or fewer of palliative radiotherapy for non-central nervous system (CNS) disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention.
- Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed or messenger ribonucleic acid (mRNA) vaccines is allowed.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (daily dose exceeding 10 mg of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- Known additional malignancy that is progressing or has required active treatment within the past 2 years.
- Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention. Has severe hypersensitivity (≥ grade 3) to pembrolizumab and/or any of its excipients.
- Has severe hypersensitivity (≥ grade 3) to pembrolizumab and/or any of its excipients.
- Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid allowed).
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- Has an active infection requiring systemic therapy.
- Has not adequately recovered from major surgery or has ongoing surgical complications.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
- Patients with pathologically confirmed Hodgkin-like RT (RT-classical Hodgkin's lymphoma \[cHL\]).
- Estimated life expectancy of \< 1 month as determined by the treating investigator.
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Matthew J Cortese
Roswell Park Cancer Institute
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 26, 2025
First Posted
March 7, 2025
Study Start
April 15, 2026
Primary Completion (Estimated)
April 1, 2029
Study Completion (Estimated)
April 1, 2030
Last Updated
March 24, 2026
Record last verified: 2026-03