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The FDA granted accelerated approved to adagrasib (Krazati), an oral targeted agent for treating locally advanced or metastatic non-small cell lung cancer (NSCLC) associated with KRAS^G12C mutations, the on Monday.

Approval was based on findings from the single-arm, phase II KRYSTAL-1 study. Of 112 patients with disease progression following standard platinum-based chemotherapy and a checkpoint inhibitor, the objective response rate (ORR) was 43% (95% CI 34-53) with adagrasib at 600 mg twice daily, given until disease progression or unacceptable toxicity, with an additional 37% of patients achieving stable disease. Median duration of response (DOR) was 8.5 months (95% CI 6.2-13.8) among the responders.

In a pooled efficacy analysis, , which included additional patients from a phase I/Ib trial, single-agent treatment with adagrasib in NSCLC was associated with a median overall survival of 14.1 months (94% CI 9.2-19.2).

With this approval, adagrasib becomes the second KRAS inhibitor approved for NSCLC patients harboring KRAS mutations, following last year's approval of sotorasib (Lumakras).

"The positive ORR and DOR results, as observed in previously treated patients with NSCLC harboring the KRAS^G12C mutation, demonstrate the effectiveness of Krazati as an option for these difficult-to-treat patients," said KRYSTAL-1 investigator Shirish Gadgeel, MD, of the Henry Ford Cancer Institute/Henry Ford Health System in Detroit, in a statement from the drugmaker.

Common adverse events (≥25%) seen in studies involving adagrasib at the approved dose -- whether for NSCLC or other tumor types -- included diarrhea, decreased appetite, nausea or vomiting, fatigue, musculoskeletal pain, hepatotoxicity, renal impairment, edema, and dyspnea. Overall, 13% of patients discontinued therapy due to adverse events.

The FDA also approved a , made by Qiagen, to test for adagrasib eligibility, with the agency noting that if no mutation is detected in plasma, tumor tissue should be tested.

Under the accelerated approval pathway, continued approval of adagrasib for this indication may be contingent upon the further demonstration of clinical benefit in a confirmatory trial.

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