Abstract CT027: Safety and preliminary efficacy of a novel LACO-Stim armored mesothelin-targeted CART therapy in advanced solid tumors

Background: UCMYM802 is an autologous mRNA-electroporated CAR-T cell therapy targeting mesothelin (MSLN), incorporating a lymphocyte-antigen-presenting cell costimulatory (LACO-Stim) molecule. This first-in-human study aimed to assess its safety, tolerability, preliminary efficacy, and pharmacokinetic/pharmacodynamic (PK/PD) profiles. Methods: This phase I study enrolled patients with metastatic or recurrent MSLN-positive solid tumors who failed standard therapies. Three dose levels were evaluated: 1×10^8 (n=1), 5×10^8 (n=1), and 1×10^9 CAR-T cells (n=7). No lymphodepletion was required prior to infusion. Patients received up to 4 weekly infusions. Primary endpoints were safety and determination of the maximum tolerated dose (MTD). Secondary endpoints included objective response rate (ORR) by RECIST v1.1, disease control rate (DCR), and PK/PD parameters. Results: As of November 2025, 9 patients were enrolled and treated (median age 67 [range 52-67]). Tumor types included pancreatic cancer (n=3), peritoneal malignant mesothelioma (n=1), adenocarcinoma of unknown primary, consistent with a gynecologic or peritoneal origin (n=1), extrahepatic cholangiocarcinoma (n=1), cholangiocarcinoma (n=1), ovarian cancer (n=1), and lung cancer (n=1). All patients received at least one infusion. The 1×10^9 dose level was defined as the MTD, with one dose-limiting toxicity (DLT) observed (grade 4 cytokine release syndrome [CRS] with hypotension). Treatment-related adverse events (TRAEs) occurred in all patients, most commonly CRS (88.9%), fever (88.9%), decreased lymphocyte count (77.8%), anemia (77.8%), prolonged prothrombin time (66.7%), and hypoxia (55.6%). Grade ≥3 CRS occurred in 25% of patients. Among seven efficacy-evaluable patients, two patients achieved partial response (PR; one each in 5×10^8 and 1×10^9 cohorts), and two had stable disease (SD; one each in 1×10^8 and 1×10^9 cohorts). The ORR was 28.6% (2/7) and DCR was 57.1% (4/7). Notable responses included a PR in gynecologic or peritoneal origin adenocarcinoma and a PR at 6 months (converted to SD at 7.5 months) in extrahepatic cholangiocarcinoma. PK analysis showed peak CAR-T expansion (by copy number) at 1-hour post-infusion, with the highest and most sustained exposure after the first infusion. PD analysis indicated IFN-γ elevation correlating with CAR-T peak expansion. CAR-T exposure and activation marker expression showed a dose-dependent trend. Conclusions: UCMYM802 demonstrated a manageable safety profile consistent with expected CAR-T-related toxicities, primarily CRS. Preliminary anti-tumor activity was observed in heavily pretreated patients with MSLN-positive advanced solid tumors, with encouraging signals in gynecologic or peritoneal origin adenocarcinoma and biliary tract cancers. The recommended dose for expansion is 1×10^9 CAR-T cells. These results support continued investigation of UCMYM802. Citation Format: Changsong Qi, Wei Li, Panpan Zhang, Dan Liu, Chang Liu, Jiarui Li, Miao Zhang, Jifang Gong, Changshun Wu, Lingling Lu, Cong Han, X Liu, Yangbing Zhao, Lin Shen. Safety and preliminary efficacy of a novel LACO-Stim armored mesothelin-targeted CART therapy in advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT027.