Results of Phase 1 CAR T-cell Therapy Study

Dr. Jesus Berdeja presents a study on the interim results from the dose-escalation phase (Part A) of CC-95266-MM-001 (NCT04674813), a phase 1 study evaluating BMS-986393 (CC-95266), an autologous CAR T-cell therapy targeting GPRC5D in R/R MM patients.

Abstract title:

Clinical Activity of BMS-986393 (CC-95266), a G Protein–Coupled Receptor Class C Group 5 Member D (GPRC5D)–Targeted Chimeric Antigen Receptor (CAR) T Cell Therapy, in Patients with Relapsed and/or Refractory (R/R) Multiple Myeloma (MM): First Results from a Phase 1, Multicenter, Open-Label Study

Purpose of the trial:

CAR T cell therapies targeting BCMA have shown remarkable response in relapsed/refractory multiple myeloma (R/R MM), but relapses are common and new approaches are necessary. The orphan receptor GPRC5D, expressed on MM cells with limited expression in other tissues, has emerged as a promising target for MM treatment. MCARH109, a CAR T cell therapy directed at GPRC5D, showed promising safety and efficacy in R/R MM patients (Blood, 2021). This study presents interim results from the dose-escalation phase (Part A) of CC-95266-MM-001 (NCT04674813), a phase 1 study evaluating BMS-986393 (CC-95266), an autologous CAR T cell therapy targeting GPRC5D in R/R MM patients.

Video summary:

Part A includes pts with ≥ 3 prior lines of therapy containing a proteasome inhibitor, an immunomodulatory agent, an anti-CD38 therapy, and, unless ineligible, a stem cell transplant. Prior BCMA-directed and CAR T cell therapies are allowed. The study follows a modified toxicity probability interval design with ≥ 3 pts per dose level. After screening and leukapheresis, pts received bridging therapy if needed, then lymphodepleting chemotherapy (fludarabine 30 mg/m2 + cyclophosphamide 300 mg/m2 daily for 3 days) followed by a single infusion of BMS-986393. Primary objectives are to determine the safety, tolerability, and maximum tolerated dose (MTD) and/or recommended phase 2 dose of BMS-986393.

Conclusions:

The safety profile of BMS-986393 was favorable at all doses tested with low-grade cytokine release syndrome (CRS) and infrequent and short-lived neurotoxicity. The maximum tolerated dose has not been reached, and dose escalation is ongoing. Early efficacy results are promising with observed antitumor responses, including complete response (CR) with minimal residual disease (MRD) negativity at 3 months. These findings support GPRC5D-directed CAR T cell therapy with BMS-986393 as a potential new treatment option in relapsed/refractory multiple myeloma (R/R MM). The dose for expansion in Part B of the study is being determined, and updated results will be presented.

Trial information:

ASH 2022: Abstract #364 (https://ash.confex.com/ash/2022/webprogram/Paper162395.html)

Authors:

Susan Bal, MD, M. Hakan Kocoglu, MD, Omar Nadeem, MD, Myo Htut, MD, Tara Gregory, MD, Larry D. Anderson Jr., MD, PhD, Luciano J. Megala Costa, MD, PhD, Tonia J. Buchholz, MS, PhD, Safiyyah Ziyad, PhD, Meng Li, PhD, Yanping Chen, PhD, Allison J. Kaeding, MD, Michael R. Burgess, MD, PhD, Kristen Hege, MD and Jesus Berdeja, MD.