mFOLFOX6 regimen

The purpose of this platform study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors combined with Standard(s) of Care (SOC) or with novel agents. The current subprotocols include the following: Subprotocol A: RMC-6236 + 5-fluorouracil-based regimens Subprotocol B: RMC-6236 + cetuximab with or without mFOLFOX6 Subprotocol C: RMC-6236 + gemcitabine + nab-paclitaxel Subprotocol D: RMC-9805 with or without RMC-6236 + 5-fluorouracil-based regimens Subprotocol E: RMC-9805 with or without RMC-6236 + cetuximab with or without mFOLFOX6 Subprotocol F: RMC-9805 with or without RMC-6236 + gemcitabine + nab-paclitaxel

To explore the efficacy and safety of short-course radiotherapy combined with mFOLFOX6, PD-1 monoclonal antibody and cetuximab (for RAS/BRAF Wild-Type)/bevacizumab (for RAS/BRAF Mutant) in High-Risk pMMR/MSS Rectal Adenocarcinoma through a prospective study, providing high-level evidence-based medical evidence for the use in the treatment of high-risk rectal cancer.

To explore the efficacy and safety of an intensified treatment regimen consisting of short-course radiotherapy followed by mFOLFOX6 chemotherapy combined with precise targeted therapy (based on RAS/BRAF status: cetuximab for wild-type, bevacizumab for mutant) and a PD-1 monoclonal antibody, compared with short-course radiotherapy followed by mFOLFOX6 chemotherapy alone, in high-risk locally advanced pMMR/MSS rectal adenocarcinoma through a prospective, randomized controlled phase III clinical study, providing high-level evidence-based medical evidence to establish a superior neoadjuvant treatment strategy for this population.