A research team from Yonsei Cancer Center has published impressive results from a phase 1 clinical trial of a next-generation KRAS G12C targeted therapy.
The trial demonstrated an objective response rate of 70 percent in lung cancer patients.
The study highlights the potential of the new therapy, D3S-001, which targets the KRAS G12C mutation. This mutation is found in about 25 percent of non-small cell lung cancer (NSCLC) patients, making it the second most common mutation after epidermal growth factor receptor (EGFR).
The only KRAS G12C targeted therapy approved by the Ministry of Food and Drug Safety is sotorasib. However, clinical data for sotorasib show an objective response rate of 37.1 percent, a median progression-free survival of 6.8 months, and an overall survival of 12.5 months, indicating a need for more effective treatments.
The phase 1 trial of D3S-001, conducted by Professors Cho Byoung-chul, Lim Sun-min, and Yu Mi-ra at the hospital, involved 25 NSCLC patients, four pancreatic cancer patients, and 12 colorectal cancer patients.
The results showed an objective response rate of 70 percent for NSCLC, 100 percent for pancreatic cancer, and 78 percent for colorectal cancer. The team also found that the response duration was longer than that of existing therapies.
Some lung cancer patients showed no resistance to the treatment and maintained therapeutic effects for over 18 months.
Preclinical trials conducted by the same research team on animal models also yielded promising results.
The studies involved transplanting tumors from KRAS G12C-mutant NSCLC patients and sotorasib-resistant patients into mice. The new therapy demonstrated superior efficacy, including a reduction in brain metastases.
“We are diligently advancing into phase 2 trials, striving to make this next-generation targeted therapy available in clinical settings,” Professor Cho said. “As many patients develop resistance to targeted therapies over time, having various treatment options is crucial for improving therapeutic outcomes.”
The study results were published in Cancer Discovery.