Yonsei Cancer Hospital: Next-Generation KRAS G12C Targeted Therapy Shows Double the Efficacy in Phase 1 Trial Compared to Existing Treatments

Professor Byungchol Cho (left) and Professor Sunmin Lim (right) at Yonsei Cancer Hospital Lung Cancer Center. Photo by Severance Hospital

The research team led by Professors Byungchol Cho and Sunmin Lim at the Yonsei Cancer Hospital Lung Cancer Center announced on May 12 that the objective response rate among patients with solid tumors, including non-small cell lung cancer, colorectal cancer, and pancreatic cancer, reached 73.5% in a phase 1 clinical trial of a next-generation KRAS G12C targeted therapy.

This study was published in Nature Medicine (IF 58.7), a world-renowned medical journal.

The KRAS gene regulates cell growth and division. The KRAS G12C mutation is the most common mutation, found in 25% of non-small cell lung cancer cases. It is also a cause of other solid tumors such as colorectal cancer and pancreatic cancer.

Sotorasib is the only KRAS G12C targeted therapy approved by the Ministry of Food and Drug Safety. According to existing clinical data, the objective response rate is 37.1%, the median progression-free survival is 6.8 months, and the overall survival is 12.5 months. This highlights the need for next-generation targeted therapies.

The research team confirmed the results of the phase 1 clinical trial for the next-generation KRAS G12C targeted therapy.

The phase 1 clinical trial included patients with non-small cell lung cancer (21 patients), colorectal cancer (9 patients), and pancreatic cancer (4 patients). The objective response rate, defined as a tumor reduction of 30% or more, was 73.5%. The rates for each cancer type were 66.7% for lung cancer, 88.9% for colorectal cancer, and 75% for pancreatic cancer.

Positive effects were also observed in patients who had failed existing treatments. Among 20 non-small cell lung cancer patients who did not respond to previous therapies, 60% showed tumor reduction, and the objective response rate reached 30%.

Colorectal cancer patients who not only had resistance to previous treatments but also had liver metastases showed good responses as well. Among the patients who showed an objective response, 78.4% maintained their treatment response for more than six months. Notably, 68.6% of all clinical trial participants showed no disease progression for over six months.

Professor Byungchol Cho stated, "Based on these encouraging phase 1 results, we are conducting multinational clinical trials to evaluate the effectiveness of both monotherapy and combination therapy. As a significant number of patients develop rapid resistance to existing targeted therapies, improving the outcomes of next-generation targeted therapies like this one is crucial."

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