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Investigational Drug Under Study in KRAS G12C–Mutant Lung Cancer

By: Joseph Cupolo
Posted: Thursday, November 7, 2019

The investigational KRAS G12C inhibitor MRTX849 yielded clinical responses in patients with non–small cell lung cancer (NSCLC) and colorectal cancer harboring KRAS G12C mutations, according to data from an ongoing phase I clinical trial presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston. Current data demonstrating preliminary activity of MRTX849 in preclinical studies and a few patients with solid tumors were published simultaneously in Cancer Discovery.

According to an ACCR press release, Pasi A. Jänne, MD, PhD, Director of the Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, and colleagues commented: “KRAS mutations are the most common oncogenic alteration in all of human cancers, and as such, finding a therapeutic approach for this subset of cancer would have tremendous clinical impact for patients [with cancer].”

As of October 11, 2019, the investigators had enrolled 17 patients with solid tumors bearing KRAS G12C mutations. All patients had metastatic disease and no active brain metastases. The initial MRTX849 dose of 150 mg once daily was escalated to 1,200 mg daily.

Of the 12 evaluable patients, 6 had metastatic NSCLC and 3 had partial responses. Of the four evaluable patients with colorectal cancer, one had a confirmed partial response. All patients with responses received the MRTX849 dose of 600 mg twice daily.

According to the investigators, adverse events included mostly grade 1 toxicities, with the most common being diarrhea and nausea. Two patients had grade 3 or higher toxicities, including fatigue and decreased appetite. “Overall, treatment with MRTX849 was well tolerated with a low incidence of grade 3 or 4 toxicities. One caveat for both the side effects and efficacy is that it is still early, and we will gain more information as additional patients are enrolled on the study,” he added.

Disclosure: The study authors’ disclosure information may be found at aacr.org.



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