FDA grants accelerated approval of Krazati in KRAS G12C non-small cell lung cancer

This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial(s).

Krazati has demonstrated a positive benefit-risk profile with accelerated approval based on the Phase II registration-enabling cohort of the KRYSTAL-1 study, evaluating Krazati 600 mg capsules administered orally twice daily in 116 patients with KRASG12C-mutated advanced NSCLC who previously received treatment with a platinum-based regimen and an immune checkpoint inhibitor. The primary efficacy endpoints were confirmed ORR and DOR as evaluated by blinded independent central review (BICR) according to response evaluation criteria in solid tumors (RECIST v1.1). The trial demonstrated an ORR of 43% (95% CI: 34-53) with 80% (95% CI: 71-87) of patients achieving disease control. The median DOR was 8.5 months (95% CI: 6.2-13.8).

In a pooled efficacy analysis (n=132) including Phase 1/1b NSCLC and registrational Phase II NSCLC cohorts from the KRYSTAL-1 study evaluating adagrasib as a single agent at 600 mg capsules orally twice daily, adagrasib showed an ORR of 44% and a disease control rate of 81% based on BICR, a median DOR of 12.5 months (95% CI, 7.3-NE) and median overall survival of 14.1 months (94% CI, 9.2-19.2).

The safety profile of Krazati was evaluated in a pooled patient population with NSCLC and other solid tumors as a single agent at 600 mg orally twice daily in 366 patients enrolled in KRYSTAL-1 and KRYSTAL-12. The most common (at least 25%) adverse reactions were nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, renal impairment, edema, dyspnea and decreased appetite. Permanent discontinuation of Krazati due to an adverse reaction occurred in 13% of patients.