Merck: FDA Grants Breakthrough Designation to Calderasib (MK‑1084) for First‑Line KRAS G12C‑Mutant Metastatic NSCLC
- FDA granted Breakthrough Therapy designation for calderasib (MK-1084) plus pembrolizumab in first-line metastatic NSCLC with KRAS G12C mutation and PD-L1 TPS ≥1%.
- Designation was supported by positive Phase 1 KANDLELIT-001 data and Merck is running a Phase 3 KANDLELIT program with five trials (004, 007, 012, 013, 015) across NSCLC and CRC.
- Calderasib, a next-generation KRAS G12C covalent inhibitor, is being developed with Taiho Pharmaceutical and Astex (Otsuka) and will be tested in combinations including KEYTRUDA, KEYTRUDA QLEX, cetuximab+mFOLFOX6, and durvalumab.
- KRAS G12C occurs in approximately 14% of NSCLC (adenocarcinoma) patients.
FDA Breakthrough designation
FDA granted Breakthrough Therapy designation for calderasib (MK-1084) combined with pembrolizumab for first-line treatment of advanced/metastatic NSCLC with KRAS G12C mutation and PD-L1 TPS ≥1%, supported by positive Phase 1 KANDLELIT-001 data.
Drug profile
Calderasib is an investigational, potent and selective next-generation covalent KRAS G12C inhibitor; the KRAS G12C mutation occurs in approximately 14% of NSCLC adenocarcinomas.
Phase 3 KANDLELIT program
Five Phase 3 trials are planned: KANDLELIT-004 (calderasib+KEYTRUDA for newly diagnosed metastatic NSCLC with PD-L1 TPS ≥50%), 007 (calderasib+KEYTRUDA QLEX in nonsquamous NSCLC regardless of PD-L1), 012 (calderasib+cetuximab+mFOLFOX6 for first-line KRAS G12C metastatic/unresectable colorectal cancer), 013 (calderasib+KEYTRUDA QLEX in certain locally advanced NSCLC after neoadjuvant/adjuvant therapy), and 015 (calderasib+durvalumab after chemoradiation in locally advanced KRAS G12C NSCLC).
Regulatory impact
Breakthrough designation enables more intensive FDA guidance on development, organizational commitment from senior reviewers, rolling review and potential eligibility for Priority Review.
Collaborations
Calderasib is being developed in collaboration with Taiho Pharmaceutical and Astex Pharmaceuticals (a subsidiary of Otsuka Pharmaceutical).
Source: Merck
