Phase 1 BCMA–dnTGFβRII armored CAR-T (BCMA CAR + TGF-β resistance)

This Phase 1, single-arm, open-label, dose-escalation/expansion study tests an “armored” BCMA-directed CAR T-cell product in adults with relapsed/refractory multiple myeloma after at least 4 prior lines, including cohorts that are BCMA therapy–exposed and BCMA-naïve. The CAR targets BCMA on malignant plasma cells, and the armoring uses a dominant-negative TGF-β receptor II (dnTGFβRII) to block TGF-β signaling that can suppress T-cell function in the marrow microenvironment, aiming to improve persistence and antitumor activity under immunosuppressive conditions. Manufacturing uses IL-7/IL-15 culture conditions intended to support a less exhausted, more memory-like T-cell phenotype (with operational advantages for expansion reliability). The sponsor is Medical College of Wisconsin (at Froedtert & the Medical College of Wisconsin), with related platform work published with Lentigen Technology/Miltenyi Biotec. For patients at this disease stage, today’s care commonly involves sequential “triple-class–exposed” regimens, salvage combinations, and BCMA-directed therapies (CAR-T or bispecific antibodies) when eligible; this trial asks whether TGF-β–insensitive BCMA CAR-T can deepen/extend responses, including after prior BCMA treatment.