European Commission Approves Adagrasib in KRAS G12C-Mutated NSCLC

In December 2022, adagrasib was granted accelerated approval by the FDA for KRAS G12C–mutated non–small cell lung cancer.

The European Commission has granted conditional marketing authorization to adagrasib (Krazati) for adult patients with KRAS G12C–mutated non–small cell lung cancer, according to a press release from Mirati.¹

Results from the phase 2 KRYSTAL-1 trial (NCT03785249), which analyzed adagrasib at 600 mg orally twice daily, led to the agent’s approval. Patients were eligible if they had previously received treatment with a platinum-based regimen and an immune checkpoint inhibitor.

“This is a meaningful day for patients living with this difficult-to-treat cancer in the European Union as we can now offer a differentiated and potentially best-in-class therapeutic option to this underserved population,” Charles Baum, MD, PhD, founder, president, and chief executive officer, Mirati Therapeutics, Inc, said in the press release.

Investigators of the phase 1b portion of the KRYSTAL-1 trial identified enduring responses and intracranial activity for the aforementioned patient population.² The intracranial objective response rate was 42.0% (95% CI, 20.3%-66.5%), with 3 patients achieving compete responses and 5 having partial responses.

In December 2022, adagrasib was granted accelerated approval by the FDA.³ At the time, Alexander I. Spira, MD, PhD, FACP, a medical oncologist and co-director of the Virginia Cancer Specialists Research Institution, and director of the Thoracic and Phase I Program and clinical assistant professor at Johns Hopkin, commented on the approval in an interview with CancerNetwork®, saying, “We already have sotorasib [Lumakras] readily approved, but [adagrasib and sotorasib] do have slightly different toxicity profiles. It's always good to have more than one class because some people do tolerate one better than the other.”

References

1. European Commission approves KRAZATI (adagrasib) as a targeted treatment option for patients with advanced non-small cell lung cancer (NSCLC) with a KRASG12C mutation. News release. Mirati. January 10, 2024. Accessed January 10, 2024. https://bit.ly/3TUw6Qc
2. Negrao MV, Spira AI, Heist RS, et al. Intracranial efficacy of adagrasib in patients from the KRYSTAL-1 trial With KRASG12C–mutated non–small-cell lung cancer who have untreated CNS metastases. J Clin Oncol. Published online June 16, 2023. doi:10.1200/JCO.23.00046
3. FDA grants accelerated approval to adagrasib for KRAS G12C-mutated NSCLC. News release. FDA. December 12, 2022. Accessed January 10, 2024. https://bit.ly/3UUVphS