53P Toripalimab with chemotherapy as first-line treatment for advanced biliary tract tumors: A preliminary analysis of safety and efficacy of an open-label phase II clinical study

For advanced biliary tract cancers (aBTC), recommended first-line chemotherapy as gemcitabine combined with cisplatin showed limited clinical benefit. Therefore, the phase II study aims to evaluate safety and efficacy of chemotherapy plus toripalimab, an anti-PD-1 antibody, in patients (pts) with aBTC. Treatment-naive pts with aBTC received toripalimab (240mg, iv, Q3W), combined with GS (gemcitabine 1000 mg/m2 iv, d1, d8 + S-1 40-60mg bid*14d, Q21d) until the disease progresses or unacceptable toxicity. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints were objective response rate (ORR) , safety and biomarker analysis. At data cutoff (Mar 24, 2020), 39 aBTC pts (female: 51.3%, median age: 64 years, median follow-up time: 10 (2-15) months) were enrolled at Shanghai Zhongshan Hospital. The primary sites of tumor were intrahepatic cholangiocarcinoma (ICC) (41%) extrahepatic cholangiocarcinoma (ECC) (12.8%), and gallbladder (GBC) (46.2%). 34 evaluable pts had a response rate of 20.6% and a 85.3% disease control rate (7 pts PR and 22 pts SD). Median PFS was 6.7 months and OS was immature. The most frequent treatment related AEs (TRAE) were leukopenia (82.1%), anemia (84.6%) and rash (56.4%). Grade III/IV non-hematological TRAEs were seen in 8 pts (20.5%), including rash (n = 3) and infection (n = 5). Grade 3/4 hematological TRAEs were seen in 69.2% pts (leukopenia (51.3%) and thrombocytopenia (17.9%)). 3 pts discontinued the study drug due to TRAE. SAE were seen in 6 pts (5 cases of infection, 1 case of mucositis) and 1 pts died of biliary obstruction complicated with infection. 29 pts were included in biomarker analysis. The most frequently mutated genes were TP53 (59%), CDKN2A (24%) and SMAD4 (21%). Pts with TP53 or ATM alterations had a shorter PFS than wild-type pts (6 months vs. 10.5 months, p=0.036, and 2.8 months vs. 8.2 months, p=0.00037, respectively). Toripalimab with chemotherapy showed well tolerability and promising efficacy in naïve aBTC. Correlative studies identified potential predictive biomarkers. These results have guided ongoing combinations with Toripalimab in BTC.