Updated results of surufatinib combined with gemcitabine and cisplatin and immune checkpoint inhibitor (ICI) for unresectable locally advanced or metastatic intrahepatic cholangiocarcinoma.

4136 Background: Advanced metastatic intrahepatic cholangiocarcinoma (ICC) was characterized by poor survival and limited therapeutic options. Surufatinib, a selective tyrosine kinase inhibitor targeting VEGFR 1, 2, and 3, FGFR1, and CSF-1R, provides dual anti-tumor action via anti-angiogenesis and tumor microenvironment regulation. Surufatinib combined with immunotherapy and chemotherapy may enhances anti-cancer effects for advanced metastatic ICC. This study evaluates the effectiveness and safety of surufatinib combined with gemcitabine, cisplatin, and immune checkpoint inhibitor (ICI) as the first-line treatment for patients with unresectable locally advanced or metastatic intrahepatic cholangiocarcinoma. Methods: This is an open-label, single-arm, single-center trial. Eligible patients who were 18 -75 years old with histologically confirmed unresectable locally advanced or metastatic ICC were enrolled. Pts received surufatinib (250mg, orally, once daily), ICI (Zimberelimab or Toripalimab, 240mg, intravenous infusion, d1, q3w), and chemotherapy (gemcitabine 1000mg/m 2 intravenous infusion, 30min, d1, d8, q3w; cisplatin 25mg/m 2 intravenous infusion, 2h, d1, d8, q3w) until disease progression, death, surgery, intolerable toxicity, or withdrawal of consent. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), conversion to surgical resection rate, pathological complete response rate (pCR), and safety. Results: By January 20, 2026, 20 pts were enrolled with median age 60 years (range: 43-70), male 50%, 100% ECOG PS 0-1, 95% stage IV. 20 pts were efficacy evaluable, 5% (1/20) pts achieved complete response (CR), 50% (10/20) pts achieved partial response (PR), 35% (7/20) pts achieved stable disease (SD). The confirmed ORR was 55%, DCR was 90%. The median PFS was 7.7m (95%Cl: 6.3-11.3 months), and the median OS was 17.8m (95%Cl: 16.1-21.8 months). The most common TEAEs of all grades were hypertension (40%), edema (15%) and vomiting (10%), 1 patient was Immune-related pneumonia occurred. No grade ≥ 3 TEAEs or new safety signals occurred. Conclusions: Surufatinib plus gemcitabine and cisplatin combined with immune checkpoint inhibitor, the chemotherapy regimen as the standard treatment in combination with targeted and immunotherapy showed preliminary anti-tumor activity and manageable toxicity for the 1L treatment of ICC, providing an additional treatment option for pts with ICC. This study has been completed and the paper has been prepared for submission, the final results details will be published after the conference. Clinical trial information: ChiCTR2400085526.