Breakthrough in BMS KRAS Inhibitor Study for NSCLC Mutation Reaches Primary Progression-Free Survival Endpoint

In a significant development for the treatment of non-small cell lung cancer (NSCLC), Bristol Myers Squibb (BMS) has announced a major achievement in their study of KRAS inhibitors. The investigational drug, known as KRAZATI®, has demonstrated promising results in a Phase 3 clinical trial, reaching the primary endpoint of progression-free survival (PFS) in patients with locally advanced or metastatic NSCLC carrying the KRASG12C mutation.

Key Findings:

The KRYSTAL-12 study, evaluating KRAZATI as a monotherapy for previously treated patients with KRASG12C-mutated NSCLC, has shown positive outcomes. The final analysis, reviewed independently by the Blind Independent Central Review (BICR), confirmed the achievement of the primary endpoint of PFS, as well as the overall response rate (ORR) as a key secondary endpoint. The study is still ongoing, with another secondary endpoint of overall survival yet to be evaluated.

Significance of the Study:

The conclusive results from this confirmatory study indicate that KRAZATI provides statistical and clinical benefits in terms of PFS and ORR when compared to standard chemotherapy as a second-line or later therapy for KRASG12C-mutated NSCLC patients. No new safety signals were observed, and the safety profile of KRAZATI remains consistent with known safety characteristics. Based on these findings, BMS plans to submit a new drug application (NDA) to the National Medical Products Administration (NMPA) in China for adagrasib (KRAZATI) as a second-line and above treatment for KRASG12C-mutated NSCLC.

Future Prospects:

In the latter half of this year, BMS will participate in the global Phase 3 KRYSTAL-7 study in the Greater China region. This study aims to evaluate the use of adagrasib in first-line treatment for KRASG12C-mutated NSCLC patients with a tumor proportion score (TPS) of ≥50%. KRAZATI received accelerated approval from the U.S. Food and Drug Administration (FDA) in December 2022 as a targeted therapy for locally advanced or metastatic NSCLC patients with KRASG12C mutations who have previously received at least one systemic therapy. Conditional marketing authorization for KRAZATI has also been granted by the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom in 2023 and the European Commission (EC) in 2024.

Broader Application of KRAZATI:

Apart from NSCLC with KRASG12C mutation, KRAZATI and combination therapies based on KRAZATI have shown promising benefits in Phase 2 clinical studies across multiple tumor types, including advanced colorectal cancer, pancreatic cancer, and other solid tumors. In February 2024, the FDA accepted a supplemental New Drug Application (sNDA) for KRAZATI in combination with cetuximab for previously treated KRASG12C-mutated locally advanced or metastatic colorectal cancer and granted it priority review designation. The Prescription Drug User Fee Act (PDUFA) target action date for this application is June 21, 2024.

The achievement of the primary endpoint in the KRYSTAL-12 study signifies a significant breakthrough in the development of KRAS inhibitors for the treatment of NSCLC patients with the KRASG12C mutation. The positive results observed in terms of progression-free survival and overall response rate highlight the potential of KRAZATI as a valuable therapeutic option in the management of this challenging disease. Further studies and regulatory submissions are underway to provide patients with access to this innovative treatment in different regions globally.