TROP2 CAREngineered Cord Blood-Derived NK Cells + Belzutifan In Pancreatic Cancer

Primary Objective: To determine the safety of TROP2 CAR/IL-15 TGFBR2 KO NK cell administered intraperitoneally and intravenously in combination with belzutifan at the flat dose of 120 mg orally daily and define the MTD/RP2D of CAR-NK cells. Primary Endpoints: Adverse events as scored by CTCAE V5.0 Dose-limiting toxicity as defined in Section 5.4 Secondary Objectives: To estimate the best objective response rate (ORR) in patients at 12 weeks after infusion. To estimate progression-free survival and overall survival. To quantify the persistence of infused allogeneic donor CAR-transduced CB-derived NK cells in the peripheral blood and peritoneal cavity in the recipient. To profile and assess the dynamic changes in the peritoneal tumor microenvironment before and after treatment using single-cell transcriptional and immune profiling on peritoneal cells at various time points before and after treatment. To estimate patient-reported symptom burden and quality of life longitudinally through treatment and follow-up. To compare changes in circulating tumor DNA (ctDNA) with response as determined by RECIST v1.1 Secondary Endpoints: Objective response rates Progression-free survival Overall survival TROP2 CAR/IL-15 TGFBR2 KO NK cell numbers in peripheral blood and peritoneal cavity vs time profile Characterization of lymphocyte populations at various time points PROMIS-19, EQ-5D-5L, and MDASI-OC PRO questionnaire responses Plasma ctDNA concentration at baselines and serial timepoints