Phase 2 CIMAvax‑EGF anti‑EGF vaccine plus KRAS G12C inhibitors in metastatic NSCLC

Roswell Park Comprehensive Cancer Center is running this Phase 2, open-label combination study testing whether adding CIMAvax‑EGF to an approved KRAS G12C inhibitor can improve disease control in advanced/metastatic KRAS G12C–mutated non-small cell lung cancer. CIMAvax‑EGF (developed by Cuba’s Center of Molecular Immunology; advanced in the US with Roswell Park) is an active immunotherapy designed to induce anti‑EGF antibodies that “soak up” circulating epidermal growth factor, reducing EGFR-pathway signaling to tumors. Patients continue either sotorasib (Amgen; covalent KRAS G12C inhibitor) once daily or adagrasib (Mirati/Bristol Myers Squibb; covalent KRAS G12C inhibitor) twice daily, with physician choice, alongside an IM CIMAvax loading series (every 2 weeks ×4) followed by maintenance (every 4 weeks up to 1 year, with less frequent dosing allowed for high-titer responders). The scientific angle is “vertical pathway suppression”: direct KRAS G12C blockade plus upstream growth-factor deprivation, aiming to delay/overcome common on-target resistance and pathway reactivation seen with KRAS G12C monotherapy. Today’s care for KRAS G12C–mutant metastatic NSCLC commonly starts with checkpoint inhibitor–based regimens (often pembrolizumab + platinum doublet) and later lines may include sotorasib or adagrasib; this trial explores whether immunologic EGF depletion can extend benefit once a KRAS G12C inhibitor is in use.