REGOMUNE: Phase II study of regorafenib plus avelumab in solid tumors—Results of the gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) cohort.

4125 Background: There is no standard treatment for patients (pts) with advanced extra-pulmonary neuroendocrine tumors (NET) and carcinomas (NEC) after failure of chemotherapy in the metastatic setting. PD-1/PD-L1 expression is frequent in these tumors. Combining anti-PD1/PDL1 agents with anti-angiogenics has been shown to be synergistic in several tumor models. Methods: This is a single-arm open-label multicentric phase II trial assessing the efficacy and safety of regorafenib (R) (160 mg QD 3weeks/4) + Avelumab (A) (10 mg/kg every 2 weeks) combination in pts with advanced or metastatic grade 2 or 3 (G2/3) gastroenteropancreatic (GEP)-NET or GEP-NEC. The primary endpoint was the confirmed objective response rate, based on central review according to RECIST 1.1. Secondary endpoints included: 1-year progression free survival (PFS), 1-year overall survival (OS), and Safety using NCI-CTCAE v5.0. Correlative studies were planned from pts tumor samples obtained at baseline. Results: Between May 2019 and Apr. 2021, 46 pts were enrolled in 6 centers. Median age was 63 (range 31 – 80). 10 pts presented with a NEC and 36 pts with a G2/3 NET. Median follow-up was 6.5 months (95% CI: 5.3 - 9.6). Median number of previous treatment lines was: 2 (range 0 – 8). 39 (84.8%) pts experienced at least 1 dose modification or treatment interruption. The most common grade 3/4 adverse events were : Hypertension (13% of pts), fatigue (13%), and diarrhea (11%). One death was related to the treatment. Among the 42 assessable pts, 7 (16.7%) achieved a partial response: 6 pts with a G2/3 NET and 1 patient with a NEC. 22 (52.4%) pts demonstrated stable disease, 22 (52.4%) pts had tumor shrinkage and 10 (23.8%) pts had progressive disease. 3 (7.1%) pts were inevaluable as per RECIST. The median duration of response was 15.5 months (95%CI: 3.7 - not reached (NR)). The median PFS and OS were 5.5 months (95% CI: 3.6 – 9.2) and NR respectively. One year OS rate was 69.4 % (95% CI: 45.1 % – 84.5 %). Conclusions: REGOMUNE is the largest prospective study ever conducted in pts with grade 2/3 GEP-NET or GEP-NEC refractory to cytotoxic chemotherapy. The R+A combination has significant clinical activity in pts with refractory disease. Full Biomarkers analyses will be presented at the meeting. Clinical trial information: NCT03475953.