New Trial to Test Novel Combination in Relapsed, Refractory MCL

Researchers are launching a new clinical trial that will evaluate the combination of the bispecific antibody glofitamab with the noncovalent Bruton tyrosine kinase (BTK) inhibitor pirtobrutinib in patients with relapsed or refractory mantle cell lymphoma (MCL) who are BTK inhibitor naive or BTK inhibitor intolerant.

Madhav R. Seshadri, MD, of the University of California San Francisco, and colleagues presented the results at the 66th American Society of Hematology Annual Meeting & Exposition. According to the study, both of these agents are active in patients with relapsed or refractory MCL.

On the basis of single-agent activity of both pirtobrutinib and glofitamab in relapsed and refractory MCL, the immunomodulatory effects of BTK inhibition, and the largely nonoverlapping toxicities these drugs, the researchers anticipate the combination of pirtobrutinib and glofitamab will be safe and highly effective for patients with relapsed and refractory MCL.

The study will have two primary objectives: evaluation of safety of the combination according to incidence and severity of adverse events in the safety lead-in cohort and examination of preliminary efficacy of the combination as determined by complete response rate in the entire population.

The phase 2 open-label study will enroll patients previously treated with an anti-CD20 antibody and an alkylating agent who are either BTK inhibitor naive or intolerant. The study is expected to enroll 30 patients.

Study treatment will be obinutuzumab 2,000 mg on cycle 1 days 1 and 2, followed by glofitamab step-up dosing of 2.5 mg on cycle 1 day 8, 10 mg on cycle 1 day 15, and 30 mg on day 1 of cycles 2 through 12 (21-day cycles). For the first six patients enrolled, treatment with pirtobrutinib 200 mg PO daily will start on cycle 2 day 8 (Cohort 1: the six patients), and for subsequent patients, treatment with  pirtobrutinib 200 mg PO daily will start on cycle 1 day 1 (Cohort 2: 24 patients).

PET and CT imaging will be performed every four to six cycles, and measurable residual disease (MRD) will be assessed by peripheral blood using ClonoSEQ assay on cycle 13 day 1 and every six cycles after that. Any patient who achieves a complete response with undetectable MRD can discontinue pirtobrutinib.

Reference

Seshadri MR, Huang C-Y, Donner H, et al. Combination of glofitamab with pirtobrutinib in BTK inhibitor (BTKi)-naive or BTKi-intolerant patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL): a multicenter phase 2 study of the University of California Hematologic Malignancies Consortium. Abstract #3042.3. Presented at the 66th American Society of Hematology Annual Meeting & Exposition; December 7-10, 2024; San Diego, California.