Glofitamab With Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma

Mantle Cell Lymphoma Clinical Trial

Official title: A Multicenter Phase 2 Study of Glofitamab With Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma

Status Not yet recruiting

Clinical Trial Summary

This phase II trial tests the safety and effectiveness of glofitamab given in combination with pirtobrutinib in treating patients with mantle cell lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Glofitamab and obinutuzumab are monoclonal antibodies that may interfere with the ability of cancer cells to grow and spread. Obinutuzumab may also reduce the risk of immune-related conditions from treatment. Pirtobrutinib is in a class of medications called kinase inhibitors. It works by blocking the action of the protein that signals cancer cells to multiply. Giving glofitamab in combination with pirtobrutinib may be safe, tolerable and/or effective in treating patients with relapsed or refractory mantle cell lymphoma.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To characterize the safety and tolerability of the combination of glofitamab and pirtobrutinib in the first six patients enrolled.

II. To evaluate the preliminary efficacy of glofitamab and pirtobrutinib in patients 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 patients 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 patients 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 patients 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 patients 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:

Patients receive obinutuzumab intravenously (IV) on days 1 and 2 of cycle 1 for a total of 2 doses. Patients receive glofitamab IV on days 8 and 15 of cycle 1 and day 1 of remaining cycles. Cycles repeat every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients receive pirtobrutinib orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) at screening, after every 4 cycles through cycle 13 and then after every 6 cycles. Patients additionally undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) at screening, a bone marrow biopsy and aspiration at cycle 13 and blood sample collection at screening and throughout study. Additionally, patients may undergo a tissue biopsy at relapse or progression.

After completion of study treatment, patients are followed up every 3 months for up to 2 years from the start of treatment. ;

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma

• NCT number: NCT06252675
• Study type: Interventional
• Source: University of California, San Francisco
• Contact: Morgan Tate
• Phone: 877-827-3222
• Email: Morgan.Tate@ucsf.edu
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 1, 2024
• Completion date: March 31, 2028