ASCO24: Krazati's Benefit in Lung Cancer Becomes Clear

Bristol Myers Squibb’s KRAS inhibitor Krazati (adagrasib) has shown significant benefits in treating patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) that carries a KRASG12C mutation. This promising development was highlighted during the recent American Society of Clinical Oncology (ASCO) annual meeting where detailed results from the Phase III KRYSTAL-12 study were presented.

The KRYSTAL-12 study compared Krazati to the standard-of-care chemotherapy as a second- or later-line treatment for these cancer patients. Findings revealed that Krazati reduced the risk of disease progression or death by 42% compared to chemotherapy. This major breakthrough supports Bristol Myers Squibb’s earlier announcement in March that the trial had met its primary endpoint of progression-free survival (PFS), paving the way for potential full approval of the drug.

The company initially obtained Krazati through a substantial acquisition, purchasing Mirati Therapeutics for $5.8 billion. In 2022, the U.S. Food and Drug Administration (FDA) granted Krazati accelerated approval for second-line treatment of KRAS-mutated NSCLC based on objective response rate (ORR) results from the KRYSTAL-1 study, which was a single-arm, mid-stage trial.

According to the ASCO presentation, the median PFS for patients on Krazati was 5.49 months, compared to 3.84 months for those receiving chemotherapy. The objective response rate was also notably higher with Krazati at 31.9%, as opposed to 9.2% for chemotherapy. Additionally, for those who responded to the treatment, the median duration of response was 8.31 months with Krazati, compared to 5.36 months for chemotherapy.

An important aspect of the study focused on patients with central nervous system (CNS) metastases at the start of treatment. In this subgroup, Krazati demonstrated a response rate of 24%, which was more than double the 11% response rate observed in the chemotherapy group.

The study is still ongoing and will continue to evaluate overall survival as a key secondary endpoint. The early findings, however, underscore Krazati’s potential to significantly improve outcomes for patients with this specific mutation of NSCLC.

In January, European Union regulators granted conditional approval for Krazati for second-line NSCLC. This decision came after a reevaluation of the initial recommendation against the drug, reflecting confidence in its efficacy and safety profile based on the latest data.

Bristol Myers Squibb’s advancements with Krazati mark a critical step forward in the treatment landscape for KRASG12C-mutated NSCLC, offering hope for better management and improved survival rates for patients. As further data emerges from the ongoing studies, the full potential of Krazati in this therapeutic area will become clearer, potentially transforming the standard of care for this challenging form of lung cancer.