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

Abstract

e16222 Background: Advanced metastatic 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 (ICC). 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 23, 2025, 20 pts were enrolled with median age 57.9 years (range: 43-70), male 50%, 85% ECOG PS 0-1, 100% stage IV. 12 pts were efficacy evaluable. 50% (6/12) pts achieved partial response (PR), 50% (6/12) pts achieved stable disease (SD). The confirmed ORR was 50%, DCR was 100%. The median PFS was 8.2m (95%Cl: 1.4-12.2 months),and the median OS had not yet matured .The most common TEAEs of all grades were myelosuppression (33.3%), abdominal pain (27.7%), hypertension (16.6%)and diarrhea (16.6%), No grade ≥ 3 TEAEs or new safety signals occurred. Conclusions: Surufatinib plus gemcitabine and cisplatin combined with immune checkpoint inhibitor, showed preliminary anti-tumor activity and manageable toxicity for the 1L treatment of ICC, providing an additional treatment option for pts with ICC. This ongoing study promises to finish updated results on efficacy in forthcoming reports. Clinical trial information: ChiCTR2400085526 .