A phase II study of nivolumab, ipilimumab, and radiation in combination with influenza vaccine in patients with pancreatic cancer (INFLUENCE).

Background: Considering strong T-cell response from influenza vaccination, we aimed to evaluate ipilimumab, nivolumab, seasonal influenza vaccine, and stereotactic body radiotherapy (SBRT) treatment efficacy in heavily pretreated patients with refractory pancreatic cancer (PC). Materials and methods: In a single-center, phase II study (NCT05116917), individuals diagnosed with PC with progressive disease (PD) after gemcitabine- or fluorouracil-containing regimens were enrolled. SBRT (15 Gy) was administered on day 1 of the first cycle. Ipilimumab (1 mg/kg) was administered every 6 weeks and was limited to a maximum of two infusions. Nivolumab (3 mg/kg) was administered every 2 weeks until either PD or unacceptable toxicity, or for a maximum duration of 1 year. The influenza vaccine was administered subcutaneously on the first day of the first cycle. The primary endpoint was objective response rate with a predefined threshold of 15%. Secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate, and safety. Results: Between 15 November 2021 and 23 May 2023, 19 patients were enrolled and treated. As of data cut-off on 11 November 2023, the median follow-up time was 2.2 months (interquartile range 1.7-4.4 months). No objective responses or stable disease was observed. The median PFS was 1.6 months [95% confidence interval (CI) 1.4-1.8 months], and the median OS was 2.2 months (95% CI 1.8-4.6 months). Treatment-related adverse events were reported in 13 patients (68%), with 3 (16%) experiencing grade 3 or higher events. Conclusion: Combined ipilimumab, nivolumab, influenza vaccine, and SBRT in patients with PC was feasible but did not lead to objective responses, and thus did not satisfy the predefined criteria for expanding to complete accrual.