Calderasib — Investigational Agent
KRAS Inhibitor · Phase 3 · Merck
Mechanism of Action
Calderasib is an oral small-molecule inhibitor that covalently and selectively binds the mutant KRAS G12C protein in its inactive GDP-bound state, locking it in the off conformation. This prevents nucleotide exchange to the active GTP-bound state, shutting down downstream RAS-RAF-MEK-ERK and PI3K signaling that drives proliferation of KRAS G12C-mutant tumors. Selectivity for the mutant cysteine spares wild-type KRAS. It is being developed both as monotherapy and in combination with pembrolizumab and other agents to deepen and prolong responses.
Investigational Indications
- KRAS G12C-mutant non-small cell lung cancer
- KRAS G12C-mutant colorectal cancer
- Other KRAS G12C solid tumors