Bristol Myers Squibb announced that the pivotal Phase 3 KRYSTAL-12 study, evaluating KRAZATI® (adagrasib) as a monotherapy in patients with pretreated locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring a KRASG12C mutation, met the primary endpoint of progression-free survival (PFS) and the key secondary endpoint of overall response rate (ORR) as assessed by Blinded Independent Central Review (BICR) at final analysis for these endpoints. The study remains ongoing to assess the additional key secondary endpoint of overall survival. Results of the confirmatory trial showed that KRAZATI demonstrated a statistically significant and clinically meaningful benefit in PFS and ORR compared to standard-of-care chemotherapy as a second-line or later treatment for these patients.

KRAZATI had no new safety signals and the safety data was consistent with the known safety profile. The U.S. FDA granted accelerated approval for KRAZATI as a targeted treatment for patients with KRASG12C-mutated locally advanced or metastatic NSCLC who have received at least one prior systemic therapy in December 2022. In 2023, Medicines and Healthcare products Regulatory Agency (MHRA) granted conditional marketing authorization for KRAZATI as a targeted treatment option for adult patients with KRASG12C-mutated advanced NSCLC and disease progression after at least one prior systemic therapy followed by the European Commission (EC) in 2024.

In addition to KRASG12C-mutated NSCLC, KRAZATI and KRAZATI-based combinations have shown encouraging meaningful benefit in Phase 2 clinical trials across several tumors, including advanced colorectal cancer, pancreatic cancer and other solid tumors. In February, the U.S. FDA accepted for priority review the supplemental new drug application (sNDA) for KRAZATI in combination with cetuximab for the treatment of patients with previously treated KRASG12C-mutated locally advanced or metastatic colorectal cancer (CRC). The FDA assigned a Prescription Drug User Fee Act (PDUFA) goal date of June 21, 2024.

Bristol Myers Squibb thanks the patients and investigators involved in the KRYSTAL-12 clinical trial. KRAZATI (adagrasib) is highly selective and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C-mutated cancers, as the KRAS protein regenerates every 24-48 hours. KRASG12C mutations act as oncogenic drivers and occur in approximately 14% of non-small cell lung cancer, 3-4% of colorectal cancer, and 1-2% of several other cancers.

In 2022, KRAZATI was granted accelerated approval for treatment of adult patients with KRASG12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. 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).

In 2023, Medicines and Healthcare products Regulatory Agency (MHRA) granted conditional marketing authorization for KRAZATI as a targeted treatment option for adult patients with KRASG12C-mutated advanced non-small cell lung cancer and disease progression after at least one prior systemic therapy followed by the European Commission (EC) in 2024. KRAZATI continues to be evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including non-small cell lung cancer and colorectal cancer. In 2022, the FDA granted breakthrough therapy designation for KRAZATI in combination with cetuximab in patients with KRASG12C-mutated advanced colorectal cancer whose cancer has progressed following prior treatment with chemotherapy and an anti-VEGF therapy.