On September Eureka Therapeutics, Inc., a clinical-stage biotechnology company developing novel T cell therapies to treat cancer, reported the publication of a study in the New England Journal of Medicine entitled "GPRC5D-Targeted CAR T Cells for Myeloma (Press release, Eureka Therapeutics, SEP 28, 2022, View Source [SID1234621525])." The study was led by Dr. Eric Smith of the Dana-Farber Cancer Institute, Dr. Renier Brentjens of the Roswell Park Comprehensive Cancer Center, and Dr. Sham Mailankody of the Memorial Sloan Kettering Cancer Center (MSK).
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The GPRC5D binder used in the study was developed by Eureka using its proprietary E-ALPHA platform in collaboration with MSK. Eureka and MSK licensed the binder to Juno Therapeutics/Bristol Myers Squib in 2016 for CAR use, and to Sanofi in 2021 for non-CAR use.
While B cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapies have generated responses in patients with multiple myeloma, relapses associated with low-to-negative expression of BCMA are common. Preclinical studies have shown the efficacy of G protein-coupled receptor, class C, group 5, member D (GPRC5D)-targeted CAR T-cell therapy in multiple myeloma, including in BCMA antigen escape models (Smith EL et al. Science Trans Med 2019).
In this study, 17 patients were enrolled and received GPRC5D CAR T-cell therapy (MCARH109), including patients who had previously received BCMA therapies. At the highest dose level (450 million CAR T cells), 1 patient had grade 4 cytokine release syndrome and neurotoxicity and 2 patients had delayed cerebellar-like toxicities; there were no treatment associated deaths. The maximum tolerated dose was identified at 150 million CAR T cells. A response was reported in 71% of the patients in the entire cohort, and in 58% of those who received the lower doses of 25 million to 150 million cells. Patients that previously relapsed after BCMA-targeted CAR T cell therapy responded similarly to those that were CAR naïve.
"The data confirms GPRC5D as an active immunotherapeutic target in multiple myeloma," said Eric Smith, M.D., Ph.D., and co-inventor of CARs for the targeting of multiple myeloma. "We look forward to advancing this program either as a stand-alone therapy or as a combination therapy with BCMA-targeting CARs."
"We are thrilled that the positive GPRC5D-directed CD28/4-1BB CAR study results were published in such a prestigious journal," said Dr. Cheng Liu, President and Chief Executive Officer at Eureka Therapeutics. "The results reaffirm our commitment to developing the next generation of safer and more effective T-cell therapies to treat patients with cancer."