Updated results of camrelizumab (Cam) plus low dose apatinib combined with gemcitabine and cisplatin (GP) as first-line therapy for advanced biliary tract cancer (BTC): A single center, phase Ib/II trial.

Abstract

e16202 Background: Combination of PD-1/PD-L1 with GP has been the standard regimen for advanced biliary tract cancer (aBTC). Apatinib, an oral TKI selectively targeting VEGFR2 has been shown to reshape the immune microenvironment and enhance the efficacy of camrelizumab (an anti-PD-1 antibody) in several cancers. We therefore designed this study to explore the efficacy and safety of apatinib plus Cam and GP in aBTC and to determine the optimal dose of apatinib when combined with Cam. Methods: This prospective, 2-part, dose escalation and expansion study enrolled patients (pts) with aBTC. Pts would receive Cam (200mg) and GP (gemcitabine 1000mg/m 2 and cisplatin 25mg/m 2 , iv, d1 and d8; up to 6 cycles) plus apatinib in 21-day cycles. In the phase Ib, The RP2D of apatinib in combination with Cam + GP was defined as 250 mg, d1-d14 as posted in ESMO 2024. The primary endpoint of phase II-dose expansion part is the objective response rate (ORR) per RECIST 1.1. Using the Simon’s Minimax two-stage design, the planned sample size is 33 evaluable pts with 80% power and alpha of 5% to detect an increase of ORR from 20% to 40%. Interim analysis would require at least 5 confirmed responses in the first 18 pts to proceed to full accrual. Results: In the expansion part, 42 pts were enrolled (27 woman and 21 men; 9 had HBV infection). At the data cut-off (Jun. 13, 2025), 38 pts had at least one post-baseline tumor assessment and the median follow-up time was 5.87 month (95% CI 4.51-7.23). Out of 38 patients, 20 (52.6%) had discontinued the trial, while 18 (47.4%) patients were still receiving the study treatment. The ORR per RECIST v1.1 is 50.0% including 19 pts who achieved a partial radiological response. The median PFS is 7.13 months (95%CI：3.40-10.86), and the median OS is not reached. Grade 3-4 treatment-related adverse events (AEs) occurred in 34(80.9%) of patients, and the most common are decreased platelet count (52.3%), decreased white blood cell count (35.7%), and increased alanine aminotransferase (14.2%). 21.4% (9/42) experienced a serious AE and no grade 5 AEs occurred. Conclusions: These results support low dose apatinib (250 mg, d1-d14, q3w) as an optimal dose combined with Cam and GP in aBTC. This combination strategy showed modest efficacy and tolerable toxicity in aBTC. Clinical trial information: NCT05742750 .