Pembrolizumab in MMR-Proficient Metastatic Colorectal Cancer Pharmacologically Primed to Trigger Hypermutation Status
Status:
Recruiting
Trial end date:
2022-12-01
Target enrollment:
Participant gender:
Summary
In this study, MMRd metastatic colorectal cancer (mCRC) patients who failed standard
therapies will undergo treatment with pembrolizumab, while RAS-extended mutated
MMR-proficient mCRC patients will be tested for o6-methylguanine-DNA-methyltransferase (MGMT)
expression (IHC) and then for MGMT promoter methylation. MGMT IHC-negative, promoter
methylation positive patients will be treated with temozolomide (TMZ). Patients progressing
under temozolomide will be tested for tumor mutational burden (TMB) and proceed to
pembrolizumab if TMB is > 20 mutations/Mb. The primary study hypothesis is that tumors with
acquired resistance to temozolomide become hypermutated and are sensitive to pembrolizumab.