adagrasib + nab-sirolimus

This combination therapy consists of adagrasib, a potent and selective small molecule inhibitor of KRAS G12C, and nab-sirolimus (ABI-009), an albumin-bound nanoparticle formulation of the mTOR inhibitor sirolimus. Adagrasib irreversibly binds to the KRAS G12C protein, locking it in its inactive GDP-bound state, thereby inhibiting downstream signaling pathways essential for tumor cell growth. Nab-sirolimus targets the mammalian target of rapamycin (mTOR) pathway, which is a key downstream node in the RAS/MAPK and PI3K/AKT signaling networks and is often implicated in resistance to KRAS inhibition. The combination is designed to provide synergistic anti-tumor activity and overcome resistance mechanisms in patients with KRAS G12C-mutated advanced solid tumors, including non-small cell lung cancer (NSCLC). This therapeutic regimen is being evaluated in the Phase 1/2 KRYSTAL-19 trial, a collaboration between Mirati Therapeutics (now part of Bristol Myers Squibb) and Aadi Bioscience.

Brand names

KrazatiFyarro

Other names

adagrasib + nanoparticle albumin-bound sirolimus