Abstract 53P
Background
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.
Methods
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.
Results
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).
Conclusions
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.
Clinical trial identification
NCT03796429.
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.