KRAZATI Shows Significant Progression-Free Survival in KRASG12C-Mutated Lung Cancer

Bristol Myers Squibb recently unveiled results from the Phase 3 KRYSTAL-12 study, which evaluated KRAZATI® (adagrasib) against standard chemotherapy for patients with locally advanced or metastatic KRASG12C-mutated non-small cell lung cancer (NSCLC) who previously underwent platinum-based chemotherapy and anti-PD-(L)1 therapy. This pivotal study demonstrated that KRAZATI significantly improved progression-free survival (PFS), the primary study endpoint, compared to docetaxel, as assessed by Blinded Independent Central Review (BICR). With a median follow-up of 9.4 months, patients treated with KRAZATI experienced a median PFS of 5.5 months, markedly better than the 3.8 months observed in the docetaxel group.

The study further highlighted a substantial overall response rate (ORR) improvement with KRAZATI, registering 32% compared to a mere 9% with docetaxel. Additionally, the median duration of response (mDOR) was longer for KRAZATI at 8.31 months, in contrast to 5.36 months for docetaxel. Notably, KRAZATI also showed a significant intracranial response among patients with central nervous system (CNS) metastases, with a 24% response rate compared to 11% for docetaxel.

The KRYSTAL-12 trial continues to evaluate overall survival as a key secondary endpoint. Safety profiles for KRAZATI were consistent with previous data, revealing no new safety signals. Treatment-related adverse events (TRAEs) of any grade were observed in 94% of patients treated with KRAZATI, compared to 86.4% for those on docetaxel. Severe TRAEs (Grade ≥3) occurred in 47% of KRAZATI patients and 46% of those on docetaxel.

At the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, these findings were presented in a late-breaking oral session, underscoring the potential of KRAZATI as a targeted treatment for KRASG12C-mutated NSCLC. Dr. Tony Mok from The Chinese University of Hong Kong emphasized the significance of these results, which reinforce adagrasib as a viable option for patients who have not responded to initial treatments.

KRAZATI received accelerated approval from the FDA in 2022 for treating adult patients with KRASG12C-mutated locally advanced or metastatic NSCLC, following at least one prior systemic therapy. This approval was based on objective response rate (ORR) and duration of response (DOR), with continued approval contingent on further confirmatory trials demonstrating clinical benefit.

Beyond NSCLC, KRAZATI has shown promising effects in Phase 2 trials for other cancers with KRASG12C mutations, including colorectal and pancreatic cancers. These encouraging results support the ongoing evaluation of KRAZATI, both as a monotherapy and in combination with other treatments, for various advanced solid tumors.

The study and its findings were funded by Mirati Therapeutics, a Bristol Myers Squibb company, underlining the collaborative effort in cancer research. KRAZATI's development aligns with Bristol Myers Squibb’s commitment to advancing cancer treatment and improving patient outcomes globally.

KRYSTAL-12 is an open-label, multicenter, randomized Phase 3 study comparing KRAZATI to standard chemotherapy for KRASG12C-mutated NSCLC patients. The study's primary endpoint is progression-free survival, with secondary endpoints including overall survival, overall response rate, duration of response, and safety.

KRASG12C-mutated NSCLC represents a significant subset of lung cancer cases, characterized by poor prognosis. KRAZATI, an oral small-molecule inhibitor, is designed to inhibit the KRASG12C protein, which is a key driver in these cancers. The FDA’s accelerated approval of KRAZATI marks a crucial step in providing targeted therapies for these patients.

Bristol Myers Squibb continues to explore innovative cancer treatments, driven by a mission to transform lives through scientific advancements. The company remains dedicated to discovering and delivering novel therapies that address unmet medical needs and improve patient care across various cancer types.