Phase III Study Assessing the Efficacy of Novel BTK Inhibitor Pirtobrutinib

The phase III BRUIN MCL-321 is currently enrolling patients to compare the efficacy of pirtobrutinib versus other Bruton’s tyrosine kinase (BTK) inhibitors in patients with heavily pretreated mantle cell lymphoma (MCL). Rodrigo Ito, MD, of Eli Lilly and Company, discussed the study’s objectives during the Society of Hematologic Oncology (SOHO) Annual Meeting.

Pirtobrutinib is a highly selective, non-covalent (reversible) BTK inhibitor that inhibits both wild-type and C481-mutated BTK with equal low nM potency.

The randomized, open-label, global trial is assessing pirtobrutinib 200 mg oral daily monotherapy versus investigator’s choice of covalent BTK inhibitor monotherapy, including ibrutinib, acalabrutinib, or zanubrutinib (per labeled doses), in patients with previously treated BTK inhibitor-naïve MCL.

The researchers plan to enroll approximately 500 patients and randomize them 1:1 to each treatment arm based on simplified MCL International Prognostic Index risk, comparator BTK inhibitor, and number of prior lines of therapy.

Eligible patients are adults with a confirmed MCL diagnosis who received one or more prior lines of therapy that did not include a BTK inhibitor. Patients with a history of current or prior central nervous system involvement; significant cardiovascular disease, stroke, or intracranial hemorrhage within six months of randomization; and those who have received allogeneic or autologous transplant or chimeric antigen receptor T-cell therapy within 60 days of randomization will be excluded.

The primary endpoint is progression-free survival (PFS) per Lugano criteria assessed by an independent review committee. Secondary endpoints include overall response rate, duration of response, investigator-assessed PFS, overall survival, event-free survival, time to treatment failure, time to next treatment, second PFS, safety and tolerability, and patient-reported outcomes.

Reference

Ito R, Eyre TA, Shah NN, et al. BRUIN MCL-321, a phase 3 open-label, randomized study of pirtobrutinib versus investigator choice of BTK inhibitor in patients with previously treated, BTK inhibitor naïve mantle cell lymphoma (trial in progress). Abstract #MCL-135. Presented at the 2022 Society of Hematologic Oncology (SOHO) Annual Meeting, September 28-October 1, 2022.