Perioperative camrelizumab plus apatinib and gemcitabine-oxaliplatin in patients with borderline resectable biliary tract malignancies: A multicenter, single-arm, phase II trial.

e16299 Background: Biliary tract malignancies are often diagnosed at advanced stages and carry a poor prognosis. While surgical resection remains the only potentially curative option, few patients are eligible at diagnosis, and recurrence rates are high even after achieving R0 resection. Preclinical and early clinical evidence suggests that combining immune checkpoint inhibitors, antiangiogenic agents, and chemotherapy may enhance tumor shrinkage and improve R0 resection rates. This multicenter phase II trial evaluates the efficacy and safety of perioperative camrelizumab plus apatinib and gemcitabine-oxaliplatin (GEMOX) in patients with borderline resectable biliary tract malignancies. Methods: Patients aged 18-75 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, pathologically confirmed biliary tract cancers, and borderline resectable disease (stage II-IIIC) were enrolled between November 2022 and December 2024. Participants received camrelizumab (200 mg every 3 weeks) and apatinib (250 mg daily) combined with gemcitabine (800 mg/m² on days 1 and 8) and oxaliplatin (85 mg/m² on day 1) for two cycles. Surgical resectability was assessed, and patients underwent surgery if feasible; otherwise, up to two additional cycles could be administered. Postoperatively, camrelizumab and S-1 were continued for up to 6 months or until disease progression or unacceptable toxicity. The primary endpoint was 1-year event-free survival (EFS) rate. Secondary endpoints included objective response rate (ORR), R0 resection rate, disease control rate (DCR), and safety. Results: Among 28 enrolled patients, the median age was 64.5 years (range: 50-75), with a male-to-female ratio of 12:16. ECOG performance status was 0 in 3 patients and 1 in 25. Cholangiocarcinoma was diagnosed in 25 patients (16 intrahepatic, 8 perihilar, 1 distal) and gallbladder carcinoma in 3. Initial staging included stage II (n = 3), IIIA (n = 4), IIIB (n = 16), and IIIC (n = 5). The ORR was 64.3% (18/28), and the DCR was 96.4% (27/28). Surgery was performed in 57.1% (16/28) of patients, and R0 resection was achieved in 87.5% (14/16). The 1-year EFS data remain immature. Grade ≥3 hematologic toxicities included neutropenia (28.6%), thrombocytopenia (14.3%), and anemia (10.7%). Grade ≥3 non-hematologic toxicities included elevated aspartate aminotransferase (14.2%), proteinuria (10.8%), and elevated thyroid-stimulating hormone (3.6%). Conclusions: Perioperative camrelizumab plus apatinib and GEMOX demonstrated high ORR and R0 resection rates in patients with borderline resectable biliary tract malignancies. Toxicities were manageable and consistent with the known safety profiles of these agents. These findings warrant further exploration of this regimen as a potentially effective multimodal treatment strategy. Clinical trial information: NCT05451290 .