Talquetamab

Having recently secured FDA approval for the first in a new class of immunomodulatory drugs for multiple myeloma, Bristol Myers Squibb continues to make advances in the field, announcing Tuesday positive data from a registrational trial of its GPRC5D-directed CAR-T cell therapy arlocabtagene autoleucel (arlo-cel). The results come from the Phase II QUINTESSENTIAL study, which investigated arlo-cel in patients with quadruple-class exposed relapsed and refractory multiple myeloma (RRMM). BMS noted that participants comprised those who have been treated with an immunomodulatory inhibitor, a proteasome inhibitor, an anti-CD38 therapy and a BCMA-targeted therapy, including prior CAR-T treatment. "As combination treatment regimens are now frequently used in earlier lines of therapy, an increasing number of people with multiple myeloma are quadruple-class exposed and resistant to currently available therapies earlier in the treatment journey, creating a critical need for new therapeutic approaches," said Lynelle Hoch, president of BMS's cell therapy organisation. Top-line results showed that the trial 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. The study also met the key secondary goal of complete response rate (CRR) in the same patient population, as well as key secondary endpoints of ORR and CRR after three or more prior lines of therapy. Although specific data were not disclosed, an earlier-stage study of arlo-cel in MM patients who had received at least three prior therapies saw an ORR of 87%, including a CRR of 53%, with median progression-free survival of 18.4 months. Hoch suggested that the latest results lay "the foundation for arlo-cel to become an important treatment option for this emerging group of patients who have been exposed to prior BCMA-targeted therapies." According to BMS, the safety profile of arlo-cel in QUINTESSENTIAL was consistent with that of other CAR-T cell therapies and other GPRC5D-targeting therapies in MM. While key opinion leaders (KOLs) who spoke to FirstWord expect arlo-cel to be used after more efficacious anti-BCMA CAR-Ts, the safety profile of BMS's therapy will be a key differentiator, especially versus Johnson & Johnson's anti-GPRC5D bispecific Talvey (talquetamab). For more, see – KOL Insight - Multiple Myeloma. Talvey won US and EU approval in 2023 for heavily pretreated MM, but is associated with skin, nail and mouth toxicities. "From a toxicity perspective, it's much more favourable than GPRC5D bispecific therapy. With GPRC5D CAR-T, there are some of those off-tumour effects in terms of the taste issues, nail issues, and skin toxicities, but they're not ongoing chronic things like they are with GPRC5D bispecifics, namely talquetamab therapy, where quality of life is severely impacted," one KOL said. The content above comes from the network. if any infringement, please contact us to modify.

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.