In the afternoon of October 21, 2023, Prof. Xu Ruihua from Sun Yat-sen University Cancer Center gave an oral presentation in the ESMO Congress 2023 entitled “Safety and efficacy of D-1553 in combination with cetuximab in KRAS^G12C mutated colorectal cancer (CRC): A phase II study”.



As a highly selective and potent KRAS^G12C inhibitor, D-1553 exhibits encouraging anti-tumor activity in CRC patients with KRAS^G12C mutations. Targeting both KRAS and EGFR pathways simultaneously may enhance the anti-tumor activity of D-1553. The ongoing multi-center phase II study is evaluating the safety and efficacy of D-1553 in combination with cetuximab in KRAS^G12C mutated CRC.


This study included patients with metastatic CRC who progressed after standard treatment. The patient must have a KRAS^G12C mutation and have not previously received treatment for KRAS^G12C. The enrolled patients received twice daily treatment with D-1553 600 mg in combination with cetuximab (standard dose). The endpoints of the study include efficacy (RECIST, v1.1), safety, and pharmacokinetics (PK).


As of April 17, 2023, a total of 29 patients were included [37.9% female; median age, 56.0 years (range 32-76); 65.5% had received ≥ 3 treatments, median 3, (range 1-6); 100% had stage IV disease at baseline, ECOG PS 0/1: 24.1%/75.9%]. As of the data deadline, 20 patients (69.0%) were still receiving treatment. Median treatment duration was 5.95 (range 1.35, 9.13) months, and the median follow-up time was 6.24 (range 2.33, 9.13) months.


The overall remission rate initially observed was 51.7% (15/29), with 9 out of 15 remission cases confirmed to have remission, and 5 of them still receiving treatment. The degree of remission remains to be confirmed. The disease control rate was 93.1% (27/29). Median progression free survival (PFS) was 7.56 months (95% CI: 5.49 Months to unknown).


Treatment-related adverse events (TRAEs) of any grade occurred in 29 patients (100%), with the most common (≥ 20%) adverse events being rash, elevated AST, elevated ALT, and paronychia, most were grade 1 or 2 in severity. Three patients (10.3%) had grade 3-4 TRAEs, all associated with cetuximab. Grade 5 TRAE was not reported. 2/29 (6.9%) patients had interruption of D-1553 dose due to TRAE, 1/29 (3.4%) patients and 5/29 (17.2%) patients had reduction and interruption of cetuximab dose due to TRAE, and 1/29 (3.4%) patients had discontinuation of cetuximab due to TRAE.


The combination therapy of D-1553 and cetuximab demonstrated a tolerable safety profile, achieving a higher remission rate compared to D-1553 monotherapy. In patients with KRAS^G12C mutant CRC undergoing severe preconditioning, the PFS phase has great potential. 



This is the first global multicenter clinical trial of KRAS^G12C inhibitor with data from a large sample size of Chinese CRC patients. Different ethnicities were observed and analyzed in the same clinical trial, and the data follow-up was relatively mature. Therefore, the early manifestation of using KRAS^G12C inhibitor for the treatment of CRC patients of different ethnicities can be more intuitively observed. This clinical study has enriched the diversity of KRAS^G12C inhibitor research, providing more effective data for KRAS^G12C inhibitors in CRC, and supporting subsequent research in Asia.

Written by: Liao Shuang, Zhai Huiwen

                                                                                                            International Office, Sun Yat-sen University Cancer Center