SynKIR-110 (mesothelin KIR-CAR/DAP12) shows early tumor shrinkage with low-grade CRS in refractory solid tumors

SynKIR-110 is an autologous mesothelin (MSLN)-targeted KIR-CAR T-cell therapy engineered to signal via the KIR/DAP12 multichain immune-receptor module (vs conventional CD3ζ CAR designs), aiming to reduce exhaustion and cytokine secretion. In this first-in-human Phase 1 dose-escalation study (STAR-101; NCT05568680) across 4 US centers, patients with refractory ovarian cancer, mesothelioma, or cholangiocarcinoma received lymphodepletion (cyclophosphamide/fludarabine) then a single IV infusion at 1, 3, or 10×10^7 transduced cells/m^2 (cohorts 1–3; n=9) with 12-month follow-up planned. No dose-limiting toxicities were reported; CRS occurred in 33% (3/9) and was ≤Grade 2 with 0% ICANS (0/9), while 56% (5/9) had hematologic AEs attributed to lymphodepletion; activity signals included tumor reductions in 4/9 (44%), including one iRECIST partial response maintained through 6 months (depth of shrinkage up to 47%)—directionally better than typical second-line chemotherapy response rates in biliary tract cancer (FOLFOX ORR ~5–10%), albeit cross-trial and with very small n.