MRTX849 Shows Clinical Response for NSCLC Patients with KRAS G12C Mutation

By Jeff Craven /alert Contributor
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Patients with non-small-cell lung cancer (NSCLC) and KRAS G12C mutations demonstrated an objective response after taking MRTX849, an investigational KRAS G12C inhibitor, according to recent results from a phase 1/2 trial.

“Patients whose tumors carry the KRAS G12C mutation have a poor prognosis, are resistant to standard of care treatment and have no available targeted therapeutic options,” Charles M. Baum, MD, PhD, president and CEO of Mirati Therapeutics, stated in a press release. “Early efficacy and safety data from this Phase 1/2 trial demonstrate the potential of a potent and effective KRAS therapy.


Cancer Cells. Source Getty Images

The phase 1/2 trial enrolled 10 patients with NSCLC, 4 patients with colorectal cancer, and 3 patients with other cancers. Patients received once-daily oral doses of MRTX849 at 150 mg, 300 mg, 600 mg, or 1,200 mg, or twice-daily oral doses at 600 mg. The researchers evaluated the safety, tolerability, pharmacodynamics and pharmacokinetics of the drug as well as the tumor response. The results were recently presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston.

“There are currently no effective targeted therapies for patients with KRAS-mutant cancers,” Pasi A. Jänne, MD, PhD, director of The Lowe Center for Thoracic Oncology at the Dana Farber Cancer Institute and study investigator, said in a press release. “KRAS mutations are the most common oncogenic alteration in all of human cancers, and as such, finding a therapeutic approach for this subset of cancers would have tremendous clinical impact for cancer patients.” 

At the cut-off date, data from 12 patients were available for evaluation. The researchers found 3 of 5 patients in the twice-daily 600 mg group with NSCLC and 1 of 2 patients with colorectal cancer achieved a partial response to MRTX849, while the other patients had stable disease. At all other dose levels, 3 of 6 patients with NSCLC and 1 of 4 patients with colorectal cancer experienced a partial response to MRTX849, while 2 NSCLC patients and 1 colorectal cancer patient reported tumor shrinkage after the first scan.

With regard to adverse events, there was one case of dose-limiting toxicity for a patient who received the once-daily 1,200 mg dose, and one case of dose-limiting toxicity in the twice-daily 600 mg group. The researchers noted that the maximum dose of MRTX849 has not currently been established, and dose-expansion enrollment for twice-daily 600 mg of MRTX849 is ongoing.

“We look forward to investigating MRTX849 in patients with a variety of KRAS G12C mutated cancers and bringing the hope of a targeted therapy to them,” said Baum.


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