A phase II trial of nivolumab and gemcitabine and S-1 as the first-line treatment in patients with advanced biliary tract cancer

[[abstract]]Background: The regimen of modified gemcitabine and S-1 (GS) is active and safe for patients with advanced biliary tract cancer (ABTC) in our previous study. Herein, we report the results of a single arm phase II of Nivolumab plus modified GS as the first-line treatment in ABTC patients. Methods: Patients with chemonaïve ABTC receive nivolumab 240 mg and 800 mg/m2 gemcitabine on day 1 plus daily 80/100/120 mg of S-1 (based on body surface area) for days 1-10, in a 2-week cycle. With Optimal Simonâs two-stage design and (p0=0.15, p1=0.35) for objective response rate (ORR, complete or partial response [CR/PR]) and given error probabilities (alpha=0.05, beta=0.1), the null hypothesis (p0) would be rejected if 10 or more patients had CR/PR among 44 evaluable cases. Tumor response was assessed by CT/MRI every 6 weeks according to RECIST v1.1. The PR should be confirmed by two consecutive image examinations. Results: Between December 2019 and December 2020, a total of 48 patients were enrolled. After a median of 6.4 months (95% CI, 4.8-8.0) follow-up, 1 patient showed pathological CR and 19 patients achieved confirmed PR. The ORR was 41.7% with additional 22 patients (45.8%) of stable disease and a long-term disease control rate of 77.1% (CR+PR+SD >12weeks). The median progression-free survival and overall survival was 8.0 (95% CI, 5.8-not reached) and not reached (95% CI, 10.7-not reached) months, respectively. All grade 3/4 chemotherapy-related adverse events (AEs) were less than 7%. Fourteen patients (35.4%) experienced immune-related AEs with skin toxicity (14.6%), hypothyroidism, hypophysitis and pneumonitis (all 6.3%). Two patients with grade 3 pneumonitis recovered well without any treatment-related death. Conclusions: By the observation of 20 patients with CR/PR, the null hypothesis was rejected. Nivolumab in combination with modified GS is a promising regimen with good safety profiles, which deserves further investigation for the management of Asian ABTC patients