A pivotal trial of Bristol Myers Squibb’s GPRC5D-directed CAR-T cell therapy has hit its primary endpoint, furthering the drugmaker’s efforts to challenge Johnson & Johnson for the post-BCMA multiple myeloma market.
BCMA-directed CAR-T cell therapies, bispecific T-cell engagers and antibody-drug conjugates have given physicians new tools for treating multiple myeloma. However, patients relapse on the drugs and, while retargeting BCMA with a different modality can trigger renewed responses, physicians eventually need an alternative treatment that hits a different target.
BMS identified arlocabtagene autoleucel (arlo-cel) as a treatment that could meet the need. To test the idea, the company gave the cell therapy to patients who had previously received an immunomodulatory inhibitor, a proteasome inhibitor, an anti-CD38 therapy and a BCMA-targeted therapy.
The single-treatment Quintessential trial met its primary endpoint, which assessed arlo-cel’s effect on overall response rate (ORR). BMS also reported a hit on the key secondary endpoint of complete response rate. The company has yet to share any data from the trial or report outcomes for its other secondary endpoints, including assessments of progression-free and overall survival.
BMS plans to share data at an upcoming medical meeting. The presentation could offer insights into how arlo-cel compares to J&J’s Talvey, a GPRC5DxCD3 bispecific antibody. J&J’s Monumental-1 trial enrolled patients who had tried a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody. Almost all patients in the J&J trial had also received a BCMA-directed T-cell engager.
J&J reported (PDF) an ORR of 72%. Early-phase data suggested arlo-cel could clear the bar set by Talvey while also offering a lower frequency, severity and duration of on-target/off-tumor adverse events. The early data supported the hypothesis that a one-time cell therapy may have a safety and tolerability edge over continuous treatment with a bispecific antibody.
BMS is running a phase 3 trial to compare arlo-cel to standard treatment regimens in patients who have received one to three prior lines of therapy and expects to publish data in 2028. Last year, the FDA said it would require CAR-T developers to show superiority over existing treatments to win approval. However, with a controlled trial underway, BMS has talked up the potential to seek approval using Quintessential.
Near-term approval would give BMS a chance to establish a foothold in a niche that could become increasingly competitive. AbbVie, AstraZeneca, Legend Biotech and Sanofi have all invested in molecules aimed at GPRC5D, while J&J’s pipeline includes a trispecific that engages BCMA and GPRC5D.