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.
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 Simon’s 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.
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.
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.
Clinical trial identification
Trial registration number NCT04172402.
Legal entity responsible for the study
Ono Pharmaceutical support Nivolumab.
L. Bai: Non-Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Other, Honoraria: Syncore, Pfizer, Lilly. L. Chen: Non-Financial Interests, Personal, Leadership Role: ScinoPharm Taiwan, Ltd.; Non-Financial Interests, Personal, Other, Honoraria: PharmaEngine, Taivex, OBI; Non-Financial Interests, Personal, Sponsor/Funding: Syncore, TTY, Pfizer, BMS, Novartis, Polaris, Merck Serono, ACTgenomics; Non-Financial Interests, Personal, Other, Patent: anti-alpha enolase (ENO-1) monoclonal antibody/HuniLife. All other authors have declared no conflicts of interest.