Regorafenib-Avelumab combination in patients with microsatellite stable colorectal cancer (REGOMUNE) : a single arm, open-label, phase II trial
Mené sur 48 patients atteints d'un cancer colorectal présentant une stabilité des microsatellites, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité d'un traitement combinant régorafénib et avélumab
Purpose: Regorafenib is synergistic with immune-checkpoint inhibition in colorectal cancer pre-clinical models. Experimental design: This is a single-arm, multicentric phase II trial. Regorafenib was given 3 weeks/4, 160mg QD; Avelumab 10 mg/kg IV was given every 2 weeks, beginning at C1D15 until progression or unacceptable toxicity. The primary endpoint was the confirmed objective response rate under treatment, as per RECIST 1.1. The secondary endpoints included: 1-year non-progression rate, progression-free survival and overall survival, safety and biomarkers studies performed on sequential tumor samples obtained at baseline and at cycle 2 Day 1. Results: 48 patients were enrolled in 4 centers. 43 were assessable for efficacy after central radiological review. Best response was stable disease for 23 patients (53.5%) and progressive disease for 17 patients (39.5%). The median progression-free survival and overall survival were 3.6 months (95%CI: [1.8 - 5.4]) and 10.8 months (95%CI: [5.9 - NA]), respectively. The most common grade 3 or 4 adverse events were palmar-plantar erythrodysesthesia syndrome (n=14, 30%), hypertension (n=11, 23%) and diarrhea (n=6, 13%). High baseline infiltration by tumour-associated macrophages was significantly associated with adverse progression-free survival (1.8 vs 3.7 months, p=0.002) and overall survival: 3.7 months vs not reached, p=0.002). Increased tumor infiltration by CD8+ T cells at C2D1 as compared to baseline was significantly associated with better outcome. Conclusions: The combination of regorafenib + avelumab mobilizes antitumor immunity in a subset of MSS-colorectal cancer patients. Computational pathology through quantification of immune cells infiltration may improve patient selection for further studies investigating this approach.