ctDNA-guided Treatment of TKI Plus PD-1 Inhibitor for Advanced pMMR/MSS Colorectal Cancer

This study is a prospective, randomized phase II controlled trial. It will include patients with histologically confirmed advanced metastatic pMMR/MSS colorectal adenocarcinoma, who have failed with treatment with fluoropyrimidine (5-fluorouracil or capecitabine), oxaliplatin, irinotecan plus bevacizumab/cetuximab (left-side RAS/BRAF wild-type) and whose peripheral blood ctDNA test shows a maxVAF level lower than 6.5%. Patients will be randomly assigned to receive a TKI + a PD-1 inhibitor (primarily fruquintinib combined with sintilimab) or standard later-line treatment options (regorafenib or fruquintinib monotherapy, at the discretion of the investigator) until disease progression, death, intolerable adverse events, or withdrawal of informed consent.