Phase II study of avelumab in combination with cetuximab as a rechallenge strategy in pre-treated RAS wild type metastatic colorectal cancer patients: CAVE (cetuximab-avelumab) colon

Abstract

Background: The immune system plays a pivotal role in modulating response to monoclonal antibodies therapy in cancer. Novel immune-checkpoint inhibitors have demonstrated potent efficacy alone and in combinations with cytotoxic agents in several cancers. In this regard, avelumab in combination with cetuximab might be a relevant re-challenge strategy in RAS wild type (WT) metastatic colorectal cancer (mCRC) patients treated in first line with chemotherapy (CT) in combination with anti-epidermal growth factor receptor (EGFR) drugs and who achieved a complete or partial response. Trial design: CAVE Colon is a single arm, multi-center phase II study designed to evaluate the efficacy of avelumab and cetuximab in pre-treated RASWT mCRC patients. Eligible patients: pathologically confirmed KRAS (exon 2, 3 and 4) and NRAS (exon 2, 3 and 4)WTmCRC treated with a first line CT in combination with an anti-EGFR agent with a major response achieved (complete or partial), who have progressed to a second line therapy, and received no prior immunotherapy. Primary endpoint is overall survival; secondary endpoints are overall response rate according to RECIST 1.1, progression free survival and safety profile. This study seeks to demonstrateamedianOS of 11months by the experimental combination for comparison with historical median OS 8.0 with standard third line treatments, which correspond to an improvement of OS at 6months from 40% to 57%.With 80%power and 1- sided 5%level test, it was estimated that it would be needed to enrol 66 patients. Considering a potential dropout of approximately 15% of patients, a total of 75 patients will be recruited. The accrual period, started in August 2018, will be 18 months and the total duration of the study will be 36months. As per April 22nd 2019, thirty-five patients have been enrolled and started the treatment with avelumab 10 mg/kg q14 as a 1-hour i.v. infusion and cetuximab at 400mg/m2 over 2-hour and subsequently 250mg/m2 q7 as 1-hour i.v. infusion until disease progression or unacceptable toxicity.