Surufatinib combined with locoregional therapies and immune checkpoint inhibitor (ICI) for treating unresectable or metastatic intrahepatic cholangiocarcinoma.

593 Background: Advanced metastatic ICC, characterized by poor survival and limited therapeutic options, may benefit from the combined use of surufatinib—a selective tyrosine kinase inhibitor targeting VEGFR 1, 2, and 3, FGFR1, and CSF-1R—and ICIs, alongside locoregional treatments like TACE, DEB-TACE, and HAIC. Methods: Eligible pts who were 18 -75 years old with histologically confirmed unresectable or metastatic intrahepatic cholangiocarcinoma were enrolled. Pts received surufatinib (250mg, orally daily), ICI, and locoregional therapies until surgery, disease progression, death, 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 and safety. Results: By July 31, 2024, 20 pts were enrolled and 10 pts were evaluated. Median age was 56.4 years (range: 36-69), with a majority being male (70%). 9 pts were pathologically confirmed as adenocarcinoma, 1patient was small bile tract type. Treatment included DEB-TACE (20%), TACE (30%), and HAIC (50%). 50% (5/10) pts achieved partial response (PR), 20% (2/10) pts accepted conversion surgery, 30% (3/10) pts achieved stable disease (SD), and the confirmed ORR was 50%, DCR was 80%. The median PFS (95%Cl: 6.9-NA months) had not yet matured, with no significant differences in survival benefits based on age or gender, though TACE showed potential benefits. The most common AEs of all grades were nausea (30%), dizziness (30%), and headache (10%), No grade ≥ 3 TEAEs or new safety signals occurred. Conclusions: Surufatinib plus immune checkpoint inhibitor, along with locoregional therapies showed preliminary anti-tumor activity and manageable toxicity for the 1L treatment of ICC, providing an additional treatment option for pts with ICC. Clinical trial information: NCT05236699 .