Significance of the Phase 3 BRUIN MCL-321 Trial of Pirtobrutinib

Michael Wang, MD, a professor in the department of lymphoma and myeloma at MD Anderson Cancer Center, discusses the background of the phase 3 BRUIN MCL-321 trial (NCT04662255) for patients with mantle cell lymphoma (MCL) and how positive results may shape the future of the MCL space.

BRUIN MCL-321 is a global, randomized, open-label, phase 3 study looking at pirtobrutinib (Jaypirca) in comparison with investigator's choice of a Bruton’s tyrosine kinase (BTK) inhibitor, either acalabrutinib (Calquence), or zanubrutinib (Brukinsa), for the treatment of patients with MCL. Eligibility for inclusion in the study is open to patients who have received at least 1 line of therapy, are BTK inhibitor naïve, and have an ECOG performance status of 0-2.

Prior to this phase 3 study, the phase 1/2 BRUIN trial (NCT03740529) assessed pirtobrutinib 200 mg given once a day in 120 patients with MCL. FIndings from this study ultimately led to the agent’s approval by the FDA for patients with relapsed/refractory MCL.

Wang notes that if this phase 3 study is successful, it will lead to pirtobrutinib being utilized prior to BTK’s for patients with MCL.

Transcription:

0:10 | Based on the phase 2 clinical trial [NCT03740529], the FDA has approved pirtobrutinib for relapsed/refractory mantle cell lymphoma in the [United States]. Based on the phase 2 clinical trial, in order to gain full approval, they designed this a phase 3 trial. In the phase 2 clinical trial, the response rate for pirtobrutinib after a BTK inhibitor was 54%, but in the patients who had not been exposed with a covalent BTK inhibitor, usage of pirtobrutinib caused efficacy of 85%. Therefore, we think that pirtobrutinib without prior BTK inhibitors can be compared with any covalent BTK inhibitor.

0:53 | Therefore, [that influenced] this phase 3 clinical trial design. If this trial is successful, pirtobrutinib will be used before the covalent BTK inhibitor usage, so this is a very significant clinical trial.