Background: Nearly 50% of patients with colorectal cancer (CRC), one of the most common cancers worldwide, develop metastatic disease. Pre-clinical data suggest that ibrutinib, a BTK inhibitor used in several hematologic malignancies, may counteract the immune tumor escape mechanism in solid tumors. Pembrolizumab, a PD-1 checkpoint inhibitor, is effective in advanced CRC with microsatellite instability, but not microsatellite stable (MSS) disease. Given ibrutinib's immune-modulatory function, it may display synergy with checkpoint inhibitors. Ibrutinib plus anti-PD-L1 or anti-CTLA-4 has shown enhanced efficacy in multiple cancers including MSS CRC, in various mouse models. abstracts Annals of Oncology Volume 31 -Issue S3 -2020 S105
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