Anti-PD1 antibody toripalimab combined with lenvatinib, or GEMOX chemotherapy combined with lenvatinib as first-line therapy in patients with advanced intrahepatic cholangiocarcinoma: a randomized, open, two-cohort Phase 2 Study

BACKGROUND: This research aimed to assess the efficacy and safety of a regimen combining lenvatinib with an anti-PD-1 antibody or chemotherapy in patients with advanced intrahepatic cholangiocarcinoma (ICC). METHODS: gemcitabine on days 1 and 8 every 3 weeks for 6-8 cycles. The primary endpoint was the objective response rate (ORR) per RECIST 1.1, with secondary endpoints included treatment-related adverse events (AEs), overall survival (OS), and progression-free survival (PFS). RESULTS: Sixty one patients were recruited, with 31 in Arm A and 30 in Arm B. The ORR of Arm A was 32.3% (10/31; 95% CI: 16.7%-51.4%), and three patients underwent surgery after tumor downstaging. The median OS was 20.3 months (95% CI: 9.3-27.1), and median PFS was 8.9 months (95% CI: 4.2-13.9). Arm B showed an ORR of 40.0% (12/30; 95% CI: 22.7%-59.4%), and one patient proceeded to surgery after downstaging. Median OS was 15.5 months (95% CI: 9.6-23.8), and median PFS was 8.0 months (95% CI: 5.0-11.4). Adverse events (AEs) related to treatment were observed in most patients, with grade 3-4 AEs in 35.5% of Arm A and 40.0% of Arm B. The most frequent AEs were fatigue (71% vs. 63%), paresthesia (45% vs. 40%), and gingivitis (45% vs. 20%). Grade 4 thrombocytopenia occurred in 6.7% of Arm B. No grade 5 AEs were observed. Peripheral blood analysis showed monocyte levels decreased in PR(partial response) patients in Arm A but increased in PR patients in Arm B. CONCLUSIONS: The Combination of lenvatinib with either anti-PD-1 antibody or GEMOX chemotherapy is a well-tolerated and effective treatment for advanced ICC. TRAIL REGISTRATION: ClinicalTrials.gov, NCT04361331.