This randomized, phase 2 multi-institutional study was designed to investigate the role of combinational immunotherapy, using nivolumab with gemcitabine/cisplatin, or nivolumab with ipilimumab in patients with untreated advanced biliary tract cancer.1
Arm A included gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8 every 3 weeks plus nivolumab 360 mg on day 1 every 3 weeks for 6 months followed by nivolumab 240 mg every 2 weeks as monotherapy for a total duration of 2 years; arm B included nivolumab 240 mg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks for 2 years, in the absence of disease progression. The primary end point was progression-free survival (PFS) at 6 months. Secondary end points included best overall response rate per immune-related RECIST, median PFS, overall survival, and safety. Exploratory objectives included biomarker analysis using sequential whole exome/transcriptome and immune cell subsets in tissue and blood.
A total of 64 eligible patients were enrolled: 32 in arm A and 32 in arm B, with a median age of 62 years (range, 20-80 years), and 90% with metastatic disease. PFS at 6 months was 64.2% in arm A and 23.4% in arm B. Median PFS was 7.4 months in arm A and 4.1 months in arm B. Median overall survival was 10.6 in arm A and 8.3 in arm B. Whereas PFS in arm B was inferior to historical controls, arm A appeared to be as effective as standard-of-care chemotherapy. A total of 40% of patients in arm A are still alive, which suggests that there may be a “tail” on the survival curve. Analyses are still pending for safety and toxicity, overall response rate, genomic analysis, and immune subset analysis.
Although arm A was not superior to standard-of-care chemotherapy, there are 2 phase 3 trials currently open globally that are accruing patients (NCT04003636 and NCT03875235). ClinicalTrials.gov number NCT03101566.
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