Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-25 @ 3:53 AM
Ignite Modification Date:
2025-12-25 @ 3:53 AM
NCT ID:
NCT06863402
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.
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.
Study:
NCT06863402
Study Brief:
Protocol Section:
NCT06863402