Merck has secured a major regulatory milestone for its experimental cancer therapy calderasib.

 

The U.S. Food and Drug Administration has granted Breakthrough Therapy designation for the drug in combination with KEYTRUDA (pembrolizumab) as a first-line treatment for patients with advanced or metastatic non-small cell lung cancer (NSCLC) carrying a KRAS G12C mutation and expressing PD-L1.

 

The designation marks the first Breakthrough Therapy recognition for calderasib and is backed by positive results from the Phase 1 KANDLELIT-001 clinical trial.

 

“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,” said Shweta Jain, vice president, global clinical development, Merck Research Laboratories. 

 

"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 FDA’s Breakthrough Therapy designation is designed to accelerate the development and review of treatments for serious or life-threatening diseases when early clinical evidence suggests they may offer substantial improvements over existing therapies. 

 

The status provides developers with enhanced FDA guidance, increased organizational support, rolling review opportunities and potential eligibility for Priority Review.

 

Calderasib targets the KRAS G12C mutation, the most common KRAS alteration seen in patients with NSCLC, occurring in roughly 14% of adenocarcinoma cases. KRAS mutations have long been considered among the most challenging targets in oncology, making advances in this area closely watched by researchers and investors alike.

 

Merck is advancing an extensive late-stage development program for calderasib, with five ongoing Phase 3 studies spanning multiple tumor types and treatment settings.

 

The trials include KANDLELIT-004, which is evaluating calderasib plus KEYTRUDA in newly diagnosed metastatic NSCLC patients with KRAS G12C mutations and high PD-L1 expression. KANDLELIT-007 is studying calderasib alongside KEYTRUDA QLEX in advanced or metastatic nonsquamous NSCLC regardless of PD-L1 status.

 

Calderasib is a next-generation, highly potent and specific KRAS G12C covalent inhibitor designed to target one of the most prevalent cancer-driving mutations found across lung, colorectal, pancreatic and other solid tumors.