Glofitamab With Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma

PRIMARY OBJECTIVES: I. To characterize the safety and tolerability of the combination of glofitamab and pirtobrutinib in the first six participants enrolled. II. To evaluate the preliminary efficacy of glofitamab and pirtobrutinib in participants with relapsed or refractory mantle cell lymphoma (MCL) as measured by complete response rate. SECONDARY OBJECTIVES: I. To evaluate the preliminary efficacy of glofitamab and pirtobrutinib in participants with relapsed or refractory MCL as measured by progression-free survival and overall survival. II. To characterize the magnitude and duration of anti-tumor activity by objective response rate and duration of response. III. To characterize the safety and tolerability of the combination of glofitamab and pirtobrutinib. IV. To evaluate the preliminary efficacy of glofitamab and pirtobrutinib in participants with relapsed or refractory MCL as measured by complete response without measurable disease (CRMRD-) rate. V. To evaluate the time-to-complete response without measurable residual disease (CRMRD-). VI. To evaluate the treatment-free interval among participants who discontinue treatment following CRMRD- status. EXPLORATORY OBJECTIVES: I. To explore associations between baseline tumor characteristics including genetic (e.g. mutations in BTK) and immune profiles (e.g. expression of co-inhibitory receptors and T cell phenotypes) and outcomes in participants administered the combination of glofitamab and pirtobrutinib. II. To explore the effects of the combination of glofitamab and pirtobrutinib on pharmacodynamic markers relating to drug mechanism (e.g. emergence of clones with mutations conferring resistance to the study combination). III. To estimate the quality of life of participants during therapy with glofitamab and pirtobrutinib. IV. To explore time-to-CRMRD- during therapy with glofitamab and pirtobrutinib. OUTLINE: Participants receive study treatments until the absence of disease progression or unacceptable toxicity. Participants may also have a bone marrow biopsy and aspiration at cycle 13 and plasma and blood samples collected throughout study for correlative research. Additionally, participants may undergo a tissue biopsy at relapse or progression. Participants are followed for 30 days after treatment discontinuation for safety. Participants who discontinue treatment due to complete response (CR) with undetectable MRD will complete in-person visits through the end of study visit, 94 weeks from start of treatment. Participants who discontinue treatment for any reason other than CR will be followed every 3 months for up to 94 weeks from start of treatment, until death, loss to follow up, study termination, or participant withdrawal.