139TiP PRECISION: A first in human, phase Ib/IIa study of osimertinib in combination with capivasertib in EGFRm advanced NSCLC patients with PIK3CA/AKT1/PTEN alterations who had progressed on osimertinib

Osimertinib (Osi) has become the standard of care for patients(pts) with EGFRm advanced NSCLC. However, drug resistance is inevitable. PIK3CA/AKT1/PTEN alterations, occurring in 10% to 16% pts after Osi, have been identified as a potential resistance mechanism to Osi. Preclinical data showed the potential anti-tumor effects of Osi combined with capivasertib (Capi), an orally pan-AKT inhibitor, in both vitro and vivo models of osimertinib-resistant tumors with PIK3CAm and PTEN alterations. Building on these findings, a clinical study was conducted to explore the synergistic effects of Osi with Capi in NSCLC pts who progress under Osi treatment due to PIK3CA/AKT/PTEN alterations.