RAHWAY, N.J., May 29, 2026
Merck (known as MSD outside the United States and Canada) has announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to calderasib (MK-1084) in combination with KEYTRUDA® (pembrolizumab) for the first-line treatment of patients with advanced or metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (TPS ≥1%). The designation marks a significant regulatory milestone for Merck’s next-generation precision oncology program and highlights the growing importance of targeting KRAS-driven cancers. Supported by promising results from the Phase 1 KANDLELIT-001 trial, the FDA’s decision reinforces the potential of calderasib to address a major unmet need in lung cancer treatment and accelerate its clinical development pathway.
FDA Recognition Highlights Promise of KRAS G12C Targeting
The FDA’s Breakthrough Therapy Designation is reserved for investigational therapies demonstrating substantial improvement over existing treatments for serious or life-threatening diseases. Calderasib is a highly potent and selective next-generation KRAS G12C covalent inhibitor, specifically designed to target one of the most frequently observed oncogenic mutations in lung cancer. Approximately 14% of patients with NSCLC adenocarcinoma harbor KRAS G12C mutations, making it one of the most important molecular targets in modern oncology.
For decades, KRAS was considered one of the most challenging cancer-driving mutations to target therapeutically. Recent scientific advances have transformed this landscape, and calderasib represents Merck’s effort to build on this momentum with a molecule engineered for enhanced potency and specificity. The FDA designation provides opportunities for increased regulatory interaction, rolling review, and potential Priority Review, all of which could accelerate the therapy’s journey toward commercialization if clinical benefits continue to be demonstrated.
Positive KANDLELIT-001 Data Support Clinical Advancement
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The designation was supported by encouraging findings from the Phase 1 KANDLELIT-001 clinical trial, which evaluated calderasib in combination with Merck’s blockbuster immunotherapy KEYTRUDA. Researchers believe the combination strategy may offer a powerful approach by simultaneously targeting the genetic driver of tumor growth while activating the immune system against cancer cells.
Merck emphasized that ongoing research continues to explore how precision medicine and immunotherapy can work together to improve outcomes for patients with advanced lung cancer. The company views calderasib as a critical component of its expanding oncology pipeline, particularly as demand grows for therapies tailored to specific molecular alterations. The achievement also underscores Merck’s commitment to developing innovative treatment options capable of improving survival and disease control in patients with difficult-to-treat cancers.
Broad Phase 3 Program Expands Opportunities Across Tumor Types
Building on the momentum generated by the FDA designation, Merck has launched an extensive global clinical development strategy through its KANDLELIT program, which includes five Phase 3 studies evaluating calderasib across multiple cancer settings. These trials are investigating combinations of calderasib with KEYTRUDA, KEYTRUDA QLEX, cetuximab, chemotherapy regimens, and other targeted therapies in NSCLC and colorectal cancer. The program spans newly diagnosed metastatic disease, locally advanced tumors, and treatment settings following prior therapies.
By targeting KRAS G12C mutations across different tumor types and stages, Merck aims to establish calderasib as a foundational therapy in precision oncology. With lung cancer remaining the leading cause of cancer-related death worldwide and more than 2.4 million new cases diagnosed annually, the advancement of targeted therapies such as calderasib could play a pivotal role in improving long-term patient outcomes. The FDA’s Breakthrough Therapy Designation therefore represents not only an important achievement for Merck but also a potentially meaningful development for patients seeking more effective treatment options against KRAS-driven cancers.
Source: Merck press release
