Adagrasib is effective for lung cancer patients with KRAS G12C and mutants

HOUSTON – Researcher from University of Texas MD Anderson Cancer Center found the inhibitor adagrasib KRAS G12C showed promising activity in suppressing cancer growth not only in the lung but also in brain metastases for patients with ACCIDENT G12C-mutations are not small cells lung cancer (NSCLC).

Findings from the Phase Ib cohort of the KRYSTAL-1 trial, published today in Journal of Clinical Oncologyrepresent the first prospective data of the anti-tumor activity of the KRAS G12C inhibitor in brain metastases, providing further evidence of the drug’s efficacy.

Targeted therapy has shown an intracranial disease control rate of 90%. In addition, the researchers observed an objective response rate (ORR) of 42% in shrinking tumors within the brain. The mean intracranial progression-free survival (PFS) was 5.4 months, while the mean overall survival (OS) was 11.4 months.

“Patients with brain metastases from KRAS-mutant lung cancer faces a poor prognosis,” said the study leader Marcelo Negrao, M.Dassistant professor of Thoracic/Head and Neck Medical Oncology. “The data suggest adagrasib may give patients a good opportunity to see responses in the brain without the need for additional therapy, such as radiation.”

KRAS mutations occur in approximately 25-30% of cases of NSCLC, with KRAS G12C mutations account for about 13% of these cases. While radiation therapy and surgery have historically been used to treat brain metastases, drugs targeted with central nervous system (CNS) penetration continue to show encouraging efficacy for the treatment of brain metastases.

Adagrasib targets the mutated KRAS protein, inhibiting its ability to promote abnormal cancer cell growth. The drug has received approval from the Food and Drug Administration for further treatment KRAS G12C– Mutant NSCLC in adult patients not responding to standard systemic therapy.

This study involved 25 patients with KRAS G12C-mutated NSCLC and untreated CNS metastases from a Phase Ib section of the ongoing KRYSTAL-1 trial. Most of the participants were women (52%) with a median age of 66 years and representatives of the predominant ethnicity of individuals who self-identify as white. Participants were given oral adagrasib at a dose of 600 mg, twice daily.

The systemic ORR in these patients was 30%. The median duration of intracranial response was 12.7 months. 37% of the patients in this study saw development of brain metastases, and only two patients saw development in the CNS alone. Results also revealed adagrab continued to exhibit a manageable safety profile, with only a few CNS-specific adverse events reported. These included changes in taste and dizziness, both of which are consistent with previous reports from the KRYSTAL-1 trial.

“Adagrasib is the first KRAS G12C inhibitor to prospectively demonstrate intracranial activity in patients with KRAS G12C-mutated NSCLC and untreated brain metastases,” said Negrao. “These findings support the ongoing clinical development of adagrasib and its combination for patients with KRAS G12C-mutated NSCLC.”

This study was sponsored by Mirati Therapeutics, Inc. A full list of collaborating authors and their disclosures can be found in the full paper Here.

Read the full release at the MD Anderson newsroom.