Randomized phase 2 study of nivolumab with or without ipilimumab in combination with stereotactic body radiotherapy in patients with refractory metastatic pancreatic cancer (CHECKPAC).

Abstract

554 Background: Pancreatic ductal adenocarcinoma remains one of the most lethal diseases. Investigating novel treatment strategies for patients with metastatic pancreatic cancer (mPC) is crucial. The purpose of this phase II trial study was to evaluate the clinical benefit of nivolumab with or without ipilimumab in combination with stereotactic body radiotherapy (SBRT) in patients with mPC. Methods: Between November 2016 and December 2019, patients with refractory mPC were randomly assigned 1:1 to SBRT of 15 Gy with nivolumab or nivolumab/ipilimumab stratified by performance status. Primary endpoint was clinical benefit rate (CBR) defined as proportion of patients with complete or partial response (PR) or stable disease, according to RECIST 1.1. Simon’s 2-stage phase II optimal design was used independently for both arms with CBR determining expansion to second stage. Secondary endpoints included safety, overall response rate, duration of response (DOR), progression free survival and overall survival (OS). Exploratory analyses included biomarkers related to immune response. Results: Eighty-four patients (41 SBRT/nivolumab and 43 SBRT/nivolumab/ipilimumab) received at least one dose of study treatment. CBR was 17.1% (95% CI, 8.0 to 30.6) for SBRT/nivolumab and 37.2% (95% CI, 24.0 to 52.1) for SBRT/nivolumab/ipilimumab. PR was observed in one patient in SBRT/nivolumab and lasted for 4.6 months. Six patients in SBRT/nivolumab/ipilimumab obtained a PR with a median DOR of 5.4 months (95% CI, 4.2 - not reached). All responders had mismatch repair proficient tumors. Grade 3 or higher treatment-related adverse events occurred in 10 (24.4%) patients in SBRT/nivolumab and in 13 (30.2%) patients in SBRT/nivolumab/ipilimumab. PD-L1 expression by tumor proportion score or combined positivity score of ≥1% was not associated with clinical benefit. On-treatment decrease in serum interleukin (IL)-6, IL-8 and CRP levels was associated with better OS. Conclusions: Clinical meaningful antitumor activity and a manageable safety profile were demonstrated after SBRT/nivolumab/ipilimumab in patients with refractory mPC. Clinical trial information: NCT02866383.