Nemtabrutinib With CAR T Therapy in Relapsed/Refractory Mantle Cell Lymphoma

PRIMARY OBJECTIVE: I. To evaluate the impact of Nemtabrutinib on efficacy of brexu-cel in relapsed or refractory (R/R) mantle cell lymphoma (MCL). SECONDARY OBJECTIVES: I. To evaluate disease response rates and survival after brexu-cel. II. To evaluate the safety of Nemtabrutinib with brexu-cel. EXPLORATORY OBJECTIVES: I. Impact of nemtabrutinib on undetectable measurable residual disease (MRD) rate after brexu-cel. II. Impact of Nemtabrutinib biological activity on recipient immune repertoire. III. Impact of Nemtabrutinib in vivo brexu-cel kinetics. IV. Mechanism of disease relapse. OUTLINE: PRE-CAR T PHASE (4-5 WEEKS): Starting 2 weeks before undergoing apheresis, patients receive nemtabrutinib orally (PO) once daily (QD) on days -40 to -6 in the absence of disease progression or unacceptable toxicity. Patients receive lymphodepleting chemotherapy fludarabine and cyclophosphamide on days -5 to -3. CAR T INFUSION PHASE (4-5 WEEKS): Patients receive brexu-cel IV on day 0. POST CAR T PHASE (UP TO 24 MONTHS): Starting around day 28 or later after brexu-cel infusion, patients without progressive disease (PD) receive nemtabrutinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 24 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo computed tomography (CT), positron emission tomography (PET)/CT or magnetic resonance imaging (MRI), bone marrow aspiration and biopsy, blood sample collection and optional tumor/lymph node biopsy throughout the study. After completion of study treatment, patients are followed up at 30 days, 12 weeks, then every 6 months for up to 5 years.