163 (PB043) - KRAS G12C mutated NSCLC and bladder cancer xenografts treated with sotorasib and adagrasib in combination with mTOR inhibitors show improved antitumor activity of nab-sirolimus vs everolimus

Abstract

Background: KRAS is frequently mutated in non-small cell lung cancer (NSCLC) and other tumor types, with KRAS G12C mutation representing ∼9% of NSCLC patients. mTOR pathway is often activated in patients with KRAS mutation and contributes to adaptive resistance to KRAS inhibitors. A combination of mTOR and KRAS inhibitors may mitigate resistance. nab-Sirolimus is a novel albumin-bound nanoparticle form of mTOR inhibitor sirolimus and is approved for the treatment of locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa).