YMN-A02 for Advanced pMMR Colorectal Cancer With Liver Metastases

This study was a prospective, single-center, open-label, single-arm, multi-dose ascending phase Ⅰ clinical trial. The investigators constructed a TM10-LNP mRNA preparation encoding CTLA-4 antibody and TGF-β trap bifunction protein (YMN-A02 bifunction RNA preparation). The aim of this study is to provide a new strategy for overcoming the immune tolerance of liver tumors and improving the response rate of immunotherapy. The investigators planned to enroll patients with advanced pMMR liver metastasis from colorectal cancer who failed standard treatment. A modified "3+3" design was used, and 10 patients were expected to be enrolled. There were four dose groups of 100μg, 250μg, 500μg and 1000μg. The trial used a modified "3+3" dose climbing design, in which one subject was set as a sentinel patient in the initial 100μg dose group. If the subject did not experience DLT during the DLT observation period, the dose was judged safe and escalation to the next group occurred. If DLT occurred, 3 additional subjects in this group would be required for further evaluation. In the subsequent 250μg, 500μg, and 1000μg dose groups, three subjects were enrolled first in each group: if there was no DLT, the number of subjects was increased. If ≥2 of the 3 cases had DLT, the escalation was terminated. If DLT occurred in 1 out of 3 subjects, 3 additional observations would be made in the same dose group. If the incidence of DLT in the total 6 subjects did not exceed 1/6 after the supplement, the escalation could be escalated. Otherwise, the escalation was terminated and the dose was considered as intolerable.