65P A single-arm, open-label, phase II study of tislelizumab combined with lenvatinib and Gemox regimen for conversion therapy of potentially resectable locally advanced biliary tract cancers

Surgery remains the only curative treatment for biliary tract cancers, and conversion therapy helps to convert locally unresectable patients to resectable patients to improve overall survival. Tislelizumab, a PD-1 monoclonal antibody, shows promising antitumor activity and safety in the treatment of advanced HCC when combined with lenvatinib. This study aimed to explore the efficacy and safety of tislelizumab combined with lenvatinib and GMOX in potentially resectable advanced BTC. In this prospective, single-center, single-arm phase II study (NCT05036798), major eligible criteria were potentially resectable locally advanced BTC, no previous systemic treatment, Child-Pugh A or B, ECOG PS 0 or 1. Patients received GMOX, followed by intravenous tislelizumab (200mg, D1, Q3W) and lenvatinib (8mg/kg, PO, QD) ≤7 cycles. Patients who remain unable to receive surgery continued to receive tislelizumab combined with lenvatinib. Primary endpoint was R0 resection rate. Secondary endpoints were progress free survival(PFS), objective response rate (ORR) and disease control rate(DCR) (RECIST 1.1). Between May 22, 2021 and January 24, 2022, 25 patients were enrolled with a median age of 59.7 years (range 33-77).11 males (44%),14 females (56%); Child-Pugh class A (n=23,92%) or B (n=2,8%); ECOG PS 0 (n=25,100%). The median tumor size was 5.3 cm (range, 1.57-11.06). As of 27 April 2022, 13 pts (52%) received R0 resection, 2 patient received intraoperative radiotherapy. 1 patient (4%) achieved complete pathological response (pCR). The median duration of therapy before surgery was 3.44 cycles (range 2-8). ORR and DCR were 56% and 92% respectively (PR, n=14; SD, n=9). Common Grade 3 treated-related adverse events (TRAEs) included leukopenia (n=3,12%), thrombocytopenia (n=3,12%), diarrhea (n=2,8%) and hypertension (n=2,8%). Tislelizumab in combination with lenvatinib and GMOX achieved a promising ORR and R0 resection conversion rate with manageable safety profile in potentially resectable locally advanced BTC. The curative effect of gallbladder cancer and ICC is better than that of HHC and ECC. Further follow-up is ongoing.