Abstract 4241: Regorafenib and nivolumab or pembrolizumab combination and ctDNA response assessment in refractory colorectal cancer

Abstract

Introduction: Patients with microsatellite stable (MSS) metastatic colorectal cancer (MCRC) are considered resistant to immunotherapy with PD-1 and PD-L1 inhibitors. However, a recent study of regorafenib and nivolumab (REGONIVO) reported high response rates and a median progression free survival (PFS) of more than 6 months (mo) in a cohort of 24 Japanese patients (pts) with MSS chemo-resistant MCRC. Methods: We evaluated the outcome of advanced MSS MCRC pts who were treated on a compassionate basis with PD-1 inhibitors in combination with regorafenib 80 mg PO QD x 21 days every 28 days in a single US center. We report their response rate (RR), PFS, and overall survival (OS). Results: 16 pts (15 males) were treated with a combination of regorafenib + PD-1 inhibitors and were evaluable for response. 14 pts received regorafenib + nivolumab (5 with prior anti-PD-1 treatment) and 2 pts received regorafenib + pembrolizumab (both following pembrolizumab treatment). No treatment-related G3 or above toxicities were attributed to the combination therapy. No objective responses were noted on treatment. 11 pts had progressive disease (PD) and 5 pts experienced stable disease (SD) as best response at 2 mo. The duration of SD was 4 mo in 2 pts (1 pt with prior anti-PD1 exposure), 6 mo in 1 pt (prior anti-PD1 exposure), 5 mo+ in 2 pt (1 with prior anti-PD1 exposure). When limiting the analysis to the 9 regorafenib and checkpoint-inhibitor naïve patients, 2 pts were noted to have SD (4 months and 5 mo+). ctDNA assays were evaluated at baseline and at 4 weeks of treatment in 11 patients. All 9 patients with a rise in ctDNA at 4 weeks had PD at the 2-mo imaging point. 2 patients with declining ctDNA at 4 weeks experienced SD for 4 mo 5 mo+, each. OS analysis remains immature as the median follow-up is only 5 mo. Conclusions: Regorafenib and nivolumab combination was associated with modest clinical activity in patients with MSS chemotherapy-resistant MCRC. This US-based small retrospective trial is at odds with the Japanese REGONIVO trial. ctDNA may represent a powerful tool for predicting progression prior to radiographic staging. Citation Format: Marwan Fakih, Dawnyel Chevalier, Janelle Saluja, Cecilia Lau, Chongkai Wang. Regorafenib and nivolumab or pembrolizumab combination and ctDNA response assessment in refractory colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4241.