Preliminary results of anlotinib and penpulimab (anti-PD1) combined with GEMOX in first-line treatment of advanced biliary tract cancer: A single-center, single-arm exploratory study.

e16195 Background: Biliary tract cancer (BTC) is a rare, yet highly aggressive malignancy, comprising approximately 3% of all gastrointestinal cancers. The KEYNOTE-966 and TOPAZ-1 trials have demonstrated the efficacy of combining immunotherapy with chemotherapy as a first-line treatment for advanced BTC. Recent studies suggest that combining immunotherapy with anti-angiogenic agents may further enhance clinical outcomes, providing opportunities for improved survival and potential conversion therapy. Anlotinib, a multi-target anti-angiogenic agent that inhibits VEGFR, PDGFR, FGFR, and c-KIT, has shown potential synergistic effects when combined with immunotherapy. This study aims to evaluate the clinical efficacy and safety of first-line treatment with anlotinib and Penpulimab in combination with GEMOX in patients with advanced BTC. Methods: Patients with histologically or pathologically confirmed unresectable or metastatic BTC (including intrahepatic cholangiocarcinoma [ICC], extrahepatic cholangiocarcinoma [ECC], and gallbladder cancer [GBC]) and at least one evaluable lesion (RECIST 1.1 criteria) were enrolled. Participants received with anlotinib (10 mg, p.o., qd, d1-14, q3w), penpulimab (200 mg, iv, d1, q3W), gemcitabine (850mg/m 2 ，iv，d1/8，q3w), and Oxaliplatin (85mg/m 2 ，iv，d1，q3w). Patients achieving a complete response (CR), partial response (PR), or stable disease (SD) were administered up to six cycles of combination chemotherapy, followed by maintenance therapy with anlotinib and penpulimab until disease progression or the onset of unacceptable toxicity. The planned sample size was 32 patients. The primary endpoint was objective response rate (ORR), with secondary endpoints including safety and progression-free survival (PFS). Results: As of December 1, 2024, 16 patients were enrolled, including 9 with ICC, 3 with ECC, and 4 with GBC, with a median age of 57 years (range: 40–73). All patients presented with stage IV disease. The preliminary ORR was 56.2% (95% CI: 29.9%–80.2%), and the DCR was 81.2% (95% CI: 54.4%–96.0%), with 1 CR, 8 PR, and 4 SD cases. At the time of data cut-off, the median PFS was 10.2 months (95% CI: 7.43–12.97). The incidence of any-grade treatment-emergent adverse events (TEAEs) was 93.8% (15/16), with grade 3 TEAEs occurring in 31.3% (5/16) of patients. The most common TEAEs were neutropenia, leukopenia, diarrhea, and hypertension. Conclusions: Anlotinib and Penpulimab combined with GEMOX as first-line therapy demonstrated promising efficacy and a manageable safety profile in patients with advanced BTC, though further data are needed to confirm these preliminary findings.