Updated phase I study results of PHE885, a T-Charge manufactured BCMA-directed CAR-T cell therapy, for patients (pts) with r/r multiple myeloma (RRMM).
Authors: Sperling Adam Samuel , Derman Benjamin Avi , Nikiforow Sarah , Im Soo-Yeon , Ikegawa Shuntaro , Prabhala Rao H. , Rodriguez Diego Hernandez , Li Yifang , Quinn David S. , Pearson David , Bu Dexiu , Mataraza Jennifer , Liegel Jessica , D'Souza Anita , Rispoli Lawrence , Credi Marc , Ritz Jerome , Jakubowiak Andrzej J. , De Vita Serena , Munshi Nikhil C. 
Published: June 2023

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Background: B cell maturation antigen (BCMA) targeted CAR-T cells are approved for RRMM. Long manufacturing time and high clinical demand limit access. T-Charge, an innovative platform that reduces manufacturing time to <2 days and preserves T cell stemness, results in robust expansion and prolonged CAR T cell persistence. Here we report updated results from the Phase I trial of T-Charge manufactured, fully human, BCMA CAR-T PHE885 (NCT04318327). Methods: Eligible pts had RRMM after ≥2 prior lines of therapy (tx). Pts received fludarabine and cyclophosphamide (or bendamustine) for lymphodepletion (LD) prior to PHE885 infusion. Primary objective was safety. Secondary objectives were clinical response and cellular kinetics. Results: As of December 22, 2022, 46 pts received PHE885 at the following doses: 2.5e6 (n=4), 5e6 (n=13), 10e6 (n=20), 14.3e6 (n=1), and 20e6 (n=8) CAR T cells. PHE885 was manufactured for 61% of pts at a single academic institution; these pts proceeded from apheresis to LD in a median of 16 days. Median age at enrollment was 65 y (range [R] 45-81), median prior lines of tx was 4 (R 2-10). 37% of pts had extramedullary disease; 96% were triple refractory. Despite aggressive disease, only 28% of pts required bridging chemotherapy, predominantly influenced by quick production time. 96% of pts experienced any gr cytokine release syndrome (CRS); 11% had gr 3 CRS. Median time to CRS onset was 8 (R 2-16) days and median duration was 4 (R 1-19) days. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 22% of pts; 7% had gr 3 ICANS. Dose limiting toxicities were experienced by 13% of pts and included gr 4 neutropenia, gr 4 lipase increase, gr 3 serum amylase increase, gr 3 neurotoxicity, gr 3 transaminitis, and gr 3 ejection fraction reduction. The most common tx-related gr ≥3 AEs included anemia (54%), neutropenia (50%), and thrombocytopenia (37%). Geo-mean peak PHE885 expansion (Cmax) was 276,000 copies/µg by qPCR and 70.6% of CD3+ T cells by flow cytometry (n=41). The PHE885 transgene was detected in 13/14 (93%) pts at 6 mo and 5/7 (71%) at 12 mo post infusion. T cells with early memory phenotype were preserved in the final product and persisted in pts post infusion. In 43 efficacy-evaluable pts, the ORR was 98%. At 10e6 dose (n=19), ORR was 100% and CRR was 42% (median follow-up of 4.9 mo [R 1.4-11.8]); 60% of 10 evaluable pts were MRD negative at 10-5 by NGS. Initial efficacy data at 20e6 and longer follow-up at active doses will also be presented. Conclusions: T-Charge manufactured PHE885 produced high response rates with no unexpected safety findings in heavily pretreated RRMM pts with aggressive disease. PHE885 expanded rapidly and showed durable persistence in vivo. Since conversion to CR/sCR has occurred as late as 18 months after infusion in this study, longer follow-up is ongoing to identify a recommended dose for future development. Clinical trial information: NCT04318327 .