LBA-004Efficacy and safety results from IMblaze370, a randomised Phase III study comparing atezolizumab+cobimetinib and atezolizumab monotherapy vs regorafenib in chemotherapy-refractory metastatic colorectal cancer

Background: Patients with chemotherapy-refractory microsatellite stable (MSS) metastatic colorectal cancer (CRC) are a population with limited treatment options and relatively short survival. Atezolizumab (an anti–PD-L1 mAb) inhibits the binding of PD-L1 to its receptors PD-1 and B7.1, leading to the re-invigoration of tumour-specific T-cell immunity. Cobimetinib inhibits MEK1/MEK2 in the MAPK pathway, and blocking the MAPK pathway has been shown to favourably alter the tumour, tumour microenvironment and T-cell responses to promote anti-tumour immune activity. We hypothesized that combining atezolizumab with cobimetinib may allow better immune recognition and generate greater anti-tumour effects than either agent alone in MSS/microsatellite instability-low (MSI-L) metastatic CRC. Here we report the primary analysis results from IMblaze370 (NCT02788279), a global, multi-centre, open-label, randomised Phase III trial comparing atezolizumab+cobimetinib and atezolizumab monotherapy with standard-of-care regorafenib in patients with previously treated, unresectable locally advanced or metastatic CRC.