Surufatinib (VEGFR/FGFR/CSF-1R TKI) + KN046 (PD-L1/CTLA-4 bispecific) with gem/nab-paclitaxel delivers 69% ORR in first-line advanced pancreatic cancer

Surufatinib, an oral multi-kinase inhibitor of VEGFR1-3, FGFR1 and CSF-1R, was combined with KN046, a dual PD-L1/CTLA-4 antibody, and the chemotherapy backbone gemcitabine 1000 mg/m² + nab-paclitaxel 125 mg/m² (q3w) in a single-arm Phase 1b/2 study (NCT05832892). Eighteen untreated, locally advanced/metastatic PDAC patients received surufatinib 200→250 mg qd (RP2D) plus KN046 5 mg/kg Day 1. Among 16 evaluable patients, the best responses were 1 CR, 10 PR and 5 SD, yielding a 68.8% ORR and 100% DCR. The mPFS was 8.3 mo (6-mo PFS 73%) and the mOS was 11.1 mo after 7.4 mo of follow-up. Grade ≥3 TRAEs—leucopenia, neutropenia, thrombocytopenia and hypertension—each occurred in 11%, with no treatment-related deaths. For context, the MPACT gem/nab regimen alone produces ~23% ORR, 5.5 mo PFS and 8.5 mo OS, while FOLFIRINOX offers a 31% ORR, 6.4 mo PFS and 11.1 mo OS—placing this triplet well above gem/nab and matching FOLFIRINOX survival with a markedly higher response rate.