Adjuvant camrelizumab combined with capecitabine in patients with intrahepatic cholangiocarcinoma after surgical resection in China (ACC): a single-arm, single-centre, open-label, phase 2 trial.

[BACKGROUND] Patients with intrahepatic cholangiocarcinoma have a poor prognosis and high postoperative recurrence rates. Immunochemotherapy has been approved as a first-line treatment for advanced biliary tract cancer. We aimed to explore the activity and safety of camrelizumab, an anti-PD-1 immunotherapy, combined with capecitabine chemotherapy in the adjuvant treatment of patients with resected intrahepatic cholangiocarcinoma.

[METHODS] ACC was a single-arm, single-centre, open-label, phase 2 trial in adult patients (aged 18-75 years) with R0-resected, pathologically confirmed intrahepatic cholangiocarcinoma (staged as IA with G3 classification or IB-III per the American Joint Committee on Cancer staging system [8th edition, 2017]) done at Zhongshan Hospital, Fudan University (Shanghai, China). Eligible patients had no extrahepatic metastases, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate organ function. 4-8 weeks after surgery, patients received eight 21-day cycles of intravenous camrelizumab (200 mg on day 1 of each cycle) plus oral capecitabine (1250 mg/m twice daily on days 1-14, followed by a 7-day rest period). The primary endpoint was recurrence-free survival, assessed in the full analysis set (FAS), which included patients who had received at least one dose of either drug. Safety was assessed in the safety set, which included patients who received at least one dose of either drug and completed at least one post-baseline safety assessment following enrolment. This study is registered with ClinicalTrials.gov (NCT04295317) and is currently ongoing but no longer recruiting new patients.

[FINDINGS] Between Sept 7, 2020, and Nov 18, 2022, 65 patients were enrolled (median age 64 years [IQR 54-70]) and included in the FAS and safety set. 40 (62%) patients were male and 25 (38%) were female. At the data cutoff of Nov 19, 2024, the median follow-up duration was 33·73 months (IQR 24·86-40·38) and 36 (55%) of 65 patients had recurrence (24 [67%] with intrahepatic recurrence only, six [17%] with both intrahepatic and extrahepatic recurrence, and six [17%] with extrahepatic recurrence only). Median recurrence-free survival was 24·29 months (95% CI 13·54-not reached). The most common treatment-related adverse events (occurring in ≥10% of patients) were reactive cutaneous capillary endothelial proliferation (45 [69%] patients), nausea (21 [32%] patients), hand-foot syndrome (19 [29%] patients), pruritus (11 [17%] patients), fatigue (11 [17%] patients), and dizziness (nine [14%] patients). Grade 3 treatment-related adverse events occurred in 15 (23%) patients, the most common of which was elevated bilirubin (two [3%] patients). Serious treatment-related adverse events were reported in four (6%) patients, including one case each of myocarditis, myalgia, type 1 diabetes, and hypothyroidism. No grade 4 treatment-related adverse events or treatment-related deaths occurred.

[INTERPRETATION] The combination of camrelizumab and capecitabine showed promising activity with an acceptable safety profile in the adjuvant setting for patients with resected intrahepatic cholangiocarcinoma. Further validation of this immunochemotherapy regimen is warranted in larger, multicentre trials.

[FUNDING] Clinical Research Special Fund, Zhongshan Hospital, Fudan University.