REGOMUNE: a phase 2 study combining regorafenib and avelumab

In REGOMUNE, the combination of regorafenib plus avelumab demonstrated progression-free survival (PFS) and overall survival (OS) results that compared favourably with historical data of regorafenib alone in patients with non-microsatellite-instability(MSI)-high metastatic colorectal cancer (mCRC). A composite score reflecting immune response of patients could be used as a biomarker in further studies to identify those who are more likely to benefit from the treatment.

The tyrosine kinase inhibitor regorafenib is approved for the management of mCRC patients who have failed standard therapy. It has been shown to reduce immunosuppressive tumour-associated macrophages (TAMs) and to synergize with anti-PD1 inhibition in a preclinical model of microsatellite-stable CRC [1,2].

REGOMUNE is a phase 1/2 study evaluating the efficacy and safety of the combination regorafenib and avelumab, an anti-PDL1 antibody, in solid tumours [3]. In Cohort A, 48 patients with non-MSI-high mCRC were enrolled. Patients were treated with regorafenib (160 mg once daily, 3 weeks on/1 week off) plus avelumab (10 mg/kg every 2 weeks) until progression of disease. Median follow-up was 7.2 months. Primary endpoint was the confirmed objective response rate, based on central review according to RECIST 1.1. Secondary endpoints included 1-year PFS, 1-year OS, and safety.

A total of 12 patients (30%) had a reduction in tumour burden. Best response was stable disease for 23 patients (57.5%) and progressive disease for 17 patients (42.5%). Median PFS was 3.6 months, median OS was 10.8 months. Increased tumour infiltration by CD8-positive T cells at day 1 of the second treatment cycle was significantly associated with better PFS and OS (P=0.011). Combining low TAM infiltration and low distance between tumour cells and CD8-positive T cells enabled the identification of a subgroup of patients (25%) who are more likely to benefit from the regorafenib plus avelumab combination: median PFS 5.3 months versus 1.9 months (P=0.037); median OS not reached versus 5.3 months (P=0.02).

Almost all patients (87%) experienced grade ≥3 adverse events. The most common grade ≥3 adverse events were palmar-plantar erythro-dysesthesia syndrome (29.8%), hypertension (23.4%), and diarrhoea (12.8%). No death was related to the treatment.

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   1. Abou-Elkacem L, et al. Mol Cancer Ther. 2013; 12: 1322-1331.
   2. Hoff S, et al. Ann Oncol 2017; 25 (suppl), abstract 11989P.
   3. Cousin S, et al. ASCO Virtual Meeting, 29-31 May 2020, Abstract 4019

Posted on 17 September, 202027 March, 2024