Nemtabrutinib With Rituximab for the Treatment of Patients With Mantle Cell Lymphoma

PRIMARY OBJECITVE: I. To evaluate the efficacy (complete response rate) of nemtabrutinib and rituximab (Nem-R) in patients with treatment-naïve mantle cell lymphoma (MCL). SECONDARY OBJECITVES: I. To evaluate objective response rate (ORR), median progression-free survival (PFS), overall survival (OS) and duration of response (DOR). II. To evaluate safety and tolerability of Nem-R in patients with treatment-naïve MCL. EXPLORATORY OBJECITVES: I. To conduct preliminary assessment of the predictive value of minimal residual disease (MRD) in MCL treated with a novel regimen. II. To explore immune cell populations in patients treated with Nem-R. III. To explore mechanisms of resistance to Nem-R therapy in MCL. IV. To estimate the second PFS after salvage therapy for patients who progress after Nem-R therapy. OUTLINE: INDUCTION: Patients receive nemtabrutinib orally (PO) once per day (QD) on days 1-28 of each cycle and rituximab intravenously (IV) on days 1, 8, 15 and 22 of cycle 1 and on day 1 of subsequent cycles. Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive nemtabrutinib PO QD on days 1-28 of each cycle and rituximab IV on day 1 of event numbered cycles. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients may optionally continue to receive nemtabrutinib PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy during screening and may undergo throughout the trial and positron emission tomography-computed tomography (PET-CT) scan and blood sample collection throughout the study. After completion of study treatment, patients are followed up at 30 days, then every 3 months for the first 2 years and every 6 months for the third year for patients in remission at the end of treatment or every 6 months for patients who end response follow up.