For instance, in the ARETHUSA [55] (NCT03519412) and MAYA (NCT03832621) trials, patients with MGMT-silenced microsatellite-stable (MSS) metastatic colorectal cancers (mCRCs) receive an induction treatment with single-agent temozolomide (TMZ), followed in the absence of disease progression by the combination of TMZ with CTLA-4 plus PD-1 blockade (MAYA trial) or by pembrolizumab at the time of tumour mutational burden (TMB) high-associated disease progression (ARETHUSA trial). The gene discussed is CTLA4; the disease is neoplasm.