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Trials / Recruiting

RecruitingNCT06863402

Nemtabrutinib and Pembrolizumab for the Treatment of Richter Transformation, Diffuse Large B-cell Lymphoma Subtype

Nemtabrutinib and Pembrolizumab in Patients With Richter Transformation: A Phase II Study

Status
Recruiting
Phase
Phase 2
Study type
Interventional
Enrollment
32 (estimated)
Sponsor
Roswell Park Cancer Institute · Academic / Other
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

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.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate the preliminary efficacy of nemtabrutinib and pembrolizumab as measured by the overall response rate (ORR) after 6 cycles for enrolled patients with Richter transformation, diffuse large B-cell lymphoma subtype (RT-DLBCL). SECONDARY OBJECTIVES: I. To further evaluate preliminary efficacy as measured by complete response rate (CRR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) for enrolled patients. II. To evaluate the safety and tolerability of nemtabrutinib and pembrolizumab combination treatment for RT-DLBCL. III. Evaluate patient-reported outcomes on quality of life and disease-related symptoms and side-effects. EXPLORATORY OBJECTIVES: I. To investigate the effects of nemtabrutinib and pembrolizumab exposure on peripheral blood mononuclear cell (PBMC) composition, particularly T-regulatory and cytotoxic T/natural killer (NK)-cell populations and correlate with clinical outcome/response. II. To investigate the impact of nemtabrutinib and pembrolizumab on the fitness, function, and "stem-like" properties of chimeric antigen receptor (CAR) T-cells manufactured from specimens both pre- and post-treatment. III. To evaluate the potential late effects of this novel combination treatment on CAR T-cell therapy and/or allogeneic hematopoietic stem cell transplant treated patients. IV. To evaluate molecular subtypes of RT-DLBCL using multiomic and probabilistic classification approaches, as well as tumor characteristics (e.g. mutational profile and total mutational burden, PD-L1 expression, etc.), and correlate with clinical outcomes for enrolled subjects. V. To evaluate pharmacokinetic (PK) and pharmacodynamic (PD) data obtained from analyses of blood specimens collected throughout treatment (for both Nemtabrutinib as well as Pembrolizumab) to enable PopPK modeling, exposure-response analyses, and integrated assessments of PK/PD data with safety, efficacy, and activity. OUTLINE: Patients receive nemtabrutinib orally (PO) once daily (QD) on days 1-21 of each cycle and pembrolizumab intravenously (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 echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening, positron emission tomography (PET)/computed tomography (CT) or CT and blood sample collection throughout the trial. Patients may also undergo bone marrow biopsy throughout the trial. After completion of study treatment, patients are followed up at 30 days then every 6 months for 3 years after completion of therapy or until death, whichever comes first, for a total of up to 5 years.

Conditions

Interventions

TypeNameDescription
PROCEDUREBiospecimen CollectionUndergo blood sample collection
PROCEDUREBone Marrow BiopsyUndergo bone marrow biopsy
PROCEDUREComputed TomographyUndergo PET/CT or CT
PROCEDUREEchocardiographyUndergo ECHO
PROCEDUREMultigated Acquisition ScanUndergo MUGA
DRUGNemtabrutinibGiven PO
BIOLOGICALPembrolizumabGiven IV
PROCEDUREPositron Emission TomographyUndergo PET/CT
OTHERQuestionnaire AdministrationAncillary studies

Timeline

Start date
2026-04-15
Primary completion
2029-04-01
Completion
2030-04-01
First posted
2025-03-07
Last updated
2026-03-24

Locations

1 site across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT06863402. Inclusion in this directory is not an endorsement.