Bristol Pulls Ahead of Amgen, Aces Confirmatory Phase III NSCLC Trial for Krazati

 Bristol Myers Squibb on Thursday released results from the Phase III KRYSTAL-12 study, showing that Krazati (adagrasib) met its primary efficacy endpoint of progression-free survival in patients with locally advanced or metastatic non-small cell lung cancer with KRAS G12C mutations.

The pharma did not provide specific data in its announcement but said that when used in the second-line setting or later, Krazati treatment led to “statistically significant and clinically meaningful” improvements in progression-free survival (PFS) versus standard-of-care chemotherapy. The KRAS blocker also elicited a significantly better overall response rate than chemotherapy.

In terms of safety, KRYSTAL-12 found no new signals of concern and Krazati’s adverse event profile was consistent with what had previously been established in prior trials.

Abderrahim Oukessou, global program lead of Krazati at BMS, in a statement called KRYSTAL-12’s findings “an important reinforcement” of the role of Krazati in treating advanced or metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC).

“Topline results of the KRYSTAL-12 confirmatory study will build greater trust in the medical and patient community,” Oukessou said.

BMS is still currently conducting a full analysis of KRYSTAL-12’s data and will share its findings with the scientific community at an upcoming medical congress. The pharma will also submit these data to health authorities.

Originally developed by Mirati, Krazati is a covalent and irreversible inhibitor of the KRAS G12C, locking the mutant protein in its inactive state and blocking its downstream signaling, without negatively affecting the wild-type protein. This mechanism of action allows Krazati to prevent the hyperactive growth of cancer cells without causing damage to healthy cells.

BMS gained access to Krazati in October 2023, when it bought Mirati for $4.8 billion.

Krazati first won the FDA’s approval in December 2022 for the treatment of adult patients with metastatic or locally advanced NSCLC harboring the KRAS G12C mutation, as determined by an FDA-approved test. Krazati is only indicated for patients who have undergone at least one prior line of systemic therapy.

This regulatory victory came via the FDA’s accelerated approval pathway, for which Mirati ran KRYSTAL-12 as a confirmatory study to keep Krazati on the market.

With the data from KRYSTAL-12, BMS now pulls ahead of Amgen which in December 2023 failed to secure the FDA’s full approval for its own KRAS blocker Lumakras (sotorasib). In October 2023, the FDA’s Oncologic Drugs Advisory Committee voted against the approval of Lumakras, pointing out that the data from the company’s CodeBreaK 200 study could not be reliably interpreted.

In its Complete Response Letter, the FDA noted that Amgen must complete an additional confirmatory study no later than February 2028 to support Lumakras’ full approval.

https://www.biospace.com/article/bms-pulls-ahead-of-amgen-aces-confirmatory-phase-iii-nsclc-trial-for-krazati/