Bristol Myers Squibb has announced positive Phase 2 results from the registrational QUINTESSENTIAL trial, evaluating arlocabtagene autoleucel (arlo-cel; BMS-986393) in adults with quadruple-class exposed Relapsed and Refractory Multiple Myeloma (RRMM).

The study met its primary endpoint, with arlo-cel demonstrating a statistically significant and clinically meaningful Overall Response Rate (ORR) in patients with quadruple-class exposed RRMM who had received four or more prior lines of therapy.

Quadruple-class exposed patients are those previously treated with an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), an anti-CD38 therapy and a B-cell maturation antigen (BCMA)-targeted therapy.

The trial also met its key secondary endpoint of Complete Response Rate (CRR) in quadruple-class exposed patients who had received four or more prior lines of therapy. Additional key secondary endpoints evaluating ORR and CRR in patients who had received three or more prior lines of therapy were also met.

The company said the safety profile of arlo-cel was consistent with that observed with other CAR T-cell therapies and GPRC5D-targeting therapies in multiple myeloma.

Arlo-cel is an investigational, autologous GPRC5D-directed CAR T-cell therapy designed to be administered as a single infusion. GPRC5D is expressed on plasma cells in multiple myeloma and represents a therapeutic target distinct from BCMA. Its expression is independent of BCMA and may be maintained following prior BCMA-directed treatment.

The QUINTESSENTIAL trial is a Phase 2, open-label, multicentre, single-arm study evaluating the efficacy and safety of arlo-cel in patients with quadruple-class exposed RRMM, including patients who had previously received CAR T-cell therapy. The primary endpoint is ORR in patients who had received four or more prior lines of therapy, while key secondary endpoints include CRR and response rates across specified treatment groups.

“These topline results support arlo-cel's potential benefit for patients while showing a safety profile consistent with expectations,” said Lynelle B. Hoch, President, Cell Therapy Organization, Bristol Myers Squibb.

The company said detailed results from the QUINTESSENTIAL study will be presented at an upcoming medical meeting.

If successful in further development and regulatory review, arlo-cel could provide an additional treatment approach for patients with heavily pretreated RRMM, particularly those whose disease has progressed following prior BCMA-targeted therapy.