New KRAS-G12C inhibitor shows breakthrough potential in cancer treatment
Hong Kong - A multinational study led by the Faculty of Medicine at The Chinese University of Hong Kong (CUHK) has found promising results for D3S-001, a next-generation KRAS-G12C inhibitor developed in mainland China. The drug has demonstrated significant anti-tumour activity, safety, and tolerability in treating solid tumours, offering renewed hope for patients with KRAS-G12C gene mutations. The findings have been published in Nature Medicine.
KRAS mutations are among the most common oncogenic drivers in solid tumours, including non-small-cell lung cancer (NSCLC), colorectal cancer, and pancreatic cancer. The KRAS-G12C mutation is particularly prevalent, occurring in 11–15% of NSCLC patients. Historically, treatment options targeting KRAS mutations have been limited, especially for colorectal cancer, which often requires combining KRAS inhibitors with anti-EGFR antibodies for effective outcomes. To address these limitations, a biotechnology company in China developed D3S-001, designed to enhance efficacy while overcoming resistance to cancer treatments.
The clinical trial, spearheaded by Professor Tony Mok Shu-kam, Li Shu Fan Professor of Clinical Oncology at CUHK, brought together researchers from South Korea, Australia, the United States, mainland China, and Hong Kong. The study focused on determining the safety, tolerability, and efficacy of D3S-001 in patients with KRAS-G12C mutations. Participants included both patients with no prior exposure to KRAS inhibitors and those who had experienced disease progression despite prior treatment. Results showed the drug was well-tolerated, with mild-to-moderate side effects such as nausea and diarrhoea. A daily dose below 600 mg proved sufficient to completely suppress the KRAS-G12C mutant protein in plasma.
The drug demonstrated a high level of efficacy in treatment-naïve patients, with over 70% achieving significant tumour shrinkage or disappearance. Additionally, more than 97% of these patients saw their disease maintained in a stable state, and 70% experienced a six-month duration of response. Even in patients who had previously developed resistance to KRAS inhibitors, D3S-001 achieved a 30% objective response rate and an 80% disease control rate. The drug’s ability to cross the blood-brain barrier was also observed, with patients showing reduced intracranial tumours or stable disease in the brain.
