Surufatinib (VEGFR/FGFR1/CSF1R TKI) + KN046 (PD-L1/CTLA-4 bispecific) + gem/nab-paclitaxel drives 71% ORR and 18.0-mo mOS in 1L advanced PDAC

Surufatinib is an oral multi-kinase inhibitor (VEGFR/FGFR1/CSF1R) with anti-angiogenic and macrophage-modulating activity, and KN046 is an IV PD-L1/CTLA-4 bispecific antibody designed to deliver dual checkpoint blockade; both were combined with gemcitabine + nab-paclitaxel in a single-arm Phase 1b/2 1L study in treatment-naïve advanced PDAC (NCT05832892) in China (n=31; 90.3% metastatic; 77.4% liver metastases). Investigator-assessed best responses were 4 CR + 18 PR + 6 SD for ORR 71.0% and DCR 90.3%; at data cut Dec 25, 2025 (median follow-up 15.9 mo), median PFS was 8.2 mo and median OS 18.0 mo with 12-mo OS 68.2%—numerically well above historical gem/nab-paclitaxel benchmarks (MPACT: ORR ~23%, mPFS 5.5 mo, mOS 8.5 mo) and also above historical FOLFIRINOX mOS 11.1 mo, recognizing cross-trial caveats and a small (n=31), China-only, immunotherapy-containing regimen. Grade ≥3 TRAEs occurred in 45.2% (most commonly hypertension 12.9%, neutropenia 12.9%, thrombocytopenia 9.7%); no treatment-related SAEs or deaths were reported; a ≥50% CA19-9 drop associated with longer PFS (10.3 vs 8.1 mo, p=0.01), while baseline liver metastases associated with worse PFS (8.0 vs NE, p=0.02).