UCMYM802 armored MSLN CAR-T (mRNA-electroporated; LACO-Stim) shows 28.6% ORR in refractory solid tumors—CRS (incl grade 4) is the main limiter

UCMYM802 is an autologous mesothelin (MSLN)-targeted CAR-T made via mRNA electroporation and “armored” with a lymphocyte–antigen-presenting cell costimulatory (LACO-Stim) module; it was evaluated in a first-in-human Phase I dose-escalation trial without lymphodepletion, allowing up to 4 weekly infusions in metastatic/recurrent MSLN+ solid tumors after standard therapies (NCT06256055). As of November 2025, 9 patients were treated across 1×10^8 (n=1), 5×10^8 (n=1), and 1×10^9 (n=7), spanning pancreatic (n=3), cholangiocarcinoma/extrahepatic cholangiocarcinoma (n=2), ovarian (n=1), mesothelioma (n=1), lung (n=1), and CUP (gynecologic/peritoneal-consistent; n=1); the MTD and recommended expansion dose were both 1×10^9 with 1 DLT (grade 4 CRS with hypotension). Safety: TRAEs occurred in 100% with CRS in 88.9% (grade ≥3 CRS 25%), plus fever 88.9%, lymphopenia 77.8%, anemia 77.8%, prolonged PT 66.7%, and hypoxia 55.6%—a CRS frequency that’s directionally higher than typical late-line chemo/immunotherapy in biliary or pancreatic cancer but is “on-mechanism” for CAR-T. Efficacy (7 evaluable): ORR 28.6% (2/7 PR) and DCR 57.1% (4/7 PR+SD), including a PR in gynecologic/peritoneal-origin adenocarcinoma and a PR lasting 6 months in extrahepatic cholangiocarcinoma (then SD at 7.5 months); in contrast, common later-line systemic options in unselected biliary tract cancer (e.g., mFOLFOX per ABC-06) and gemcitabine-refractory pancreatic cancer regimens generally deliver low-to-modest response rates (often single digits to teens), though cross-trial comparisons are especially shaky here given the tiny, histology-mixed dataset. PK/PD: CAR-T copy number peaked at ~1 hour post-infusion with strongest/sustained exposure after the first infusion, and IFN-γ increases tracked with CAR-T expansion, with dose-dependent exposure/activation marker trends.