Merck recently announced that calderasib (MK-1084), an investigational oral specific KRAS G12C inhibitor, in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, has been granted Breakthrough Therapy Designation by the US Food and Drug Administration (FDA) for the first-line treatment of patients with advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) with KRAS G12C-mutation and expressing PD-L1 (tumor proportion score [TPS] ≥1 percent). This is the first Breakthrough Therapy Designation for calderasib and was supported by positive data from the phase 1 KANDLELIT-001 trial.

Dr. Shweta Jain, Vice President—Global Clinical Development, Merck Research Laboratories, said, “As our understanding of cancer biology and precision medicine continues to advance, we’re encouraged by the potential of new approaches, like calderasib, to help address the underlying drivers of cancer growth. The Breakthrough Therapy designation for calderasib underscores the promising potential of this medicine and unmet need for certain patients with KRAS G12C-mutated NSCLC.”

The KRAS G12C mutation is the most frequently observed KRAS mutation in patients, occurring in approximately 14 percent of patients with NSCLC (adenocarcinoma).

The FDA’s Breakthrough Therapy Designation is granted to expedite the development and review of medicines that are intended to treat serious or life-threatening conditions. To qualify for this designation, preliminary clinical evidence must indicate that the product may demonstrate substantial improvement on a clinically significant endpoint over available therapies. The benefits of this Breakthrough Therapy Designation include more intensive guidance from the FDA on an efficient development program, organisational commitment involving senior managers and experienced review staff, rolling review and potential eligibility for Priority Review (PR).

Calderasib is being developed through a collaboration with Taiho Pharmaceutical and Astex Pharmaceuticals (UK), a wholly owned subsidiary of Otsuka Pharmaceutical. This collaboration was announced in January 2020.