137P - A single-arm, multicenter, phase II study of hepatic arterial infusion chemotherapy (HAIC) combined with donafenib and sintilimab as first-line treatment for unresectable intrahepatic cholangiocarcinoma (CHANCE 2203)

Background

Advanced intrahepatic cholangiocarcinoma (ICC) has a dismal prognosis. Cytotoxic agents, targeted therapy and immunotherapy-based combination strategies represent a promising treatment option for ICC. Here, we evaluated the efficacy and safety of donafenib, sintilimab, and GEMOX-based hepatic arterial infusion chemotherapy (GEMOX-HAIC) combination therapy as first-line choice for unresectable ICC.

Methods

In this multicenter, single-arm, phase Ⅱ trial, the main inclusion criteria were as follows: 18–75 years old; histopathologically confirmed unresectable and treatment-naive ICC with measurable lesion per RECIST 1.1; Eastern Cooperative Oncology Group performance status score ≤1; Child–Pugh score ≤7. Enrolled patients receive GEMOX-HAIC (gemcitabine 1000 mg/m², oxaliplatin 85 mg/m², D1, Q3W, 4-6 cycles), along with donafenib (oral, 100 mg, BID, no more than 24 months) and sintilimab (intravenously, 200 mg, Q3W, no more than 24 months). The primary endpoint was overall response rate (ORR).

Results

Between June 2022 and December 2023, 21 (13 male and 8 female, mean age of 66.8 ± 7.3 years old) unresectable ICC patients (6 at TNM stage Ⅲa, 7 at stage Ⅲb and 8 at stage Ⅳ) from 6 centers were enrolled. Until May 10, 2024, the median follow-up time was 11.6 months (range 4.3-22.9). Eight patients achieved partial response, eleven patients achieved stable disease, and two patients exhibited disease progression. Hence, the ORR was 38.1% (8/21; 95% CI: 18.1%-61.6%) and the disease control rate (DCR) was 90.5% (19/21; 95% CI: 69.6%-98.8%). The median PFS was 8.4 months (95% CI, 5.4-NR), and the median DOR and OS were not reached yet. The 6-month and 9-month OS rates yielded 84.8% (95% CI: 59.7%-94.9%) and 76.3% (95% CI: 46.8%-90.8%), respectively. Any grade adverse events (AEs) occurred in 20 patients (95.2%). 42.9% (9/21) of the patients experienced grade 3 or 4 AEs, including rash (6/21, 28.6%), leukopenia (2/21, 9.5%) and fever (2/21, 9.5%).

Conclusions

The preliminary results demonstrated the promising future of donafenib plus sintilimab and GEMOX-HAIC as a first-line choice for unresectable ICC.

Clinical trial identification

NCT05348811.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.