Osimertinib Plus Capivasertib in NSCLC With PIK3CA/AKT1/PTEN Alterations Following Prior 1L Osimertinib

The goal of this clinical trial is to learn if Osimertinib plus Capivasertib works to treat EGFRm advanced non-small cell lung cancer (NSCLC) in participants with PIK3CA/AKT1/PTEN alterations after progression on first-line Osimertinib (monotherapy or plus chemotherapy). The main questions it aims to answer are: Part A: * Number of Dose-limiting toxicities (DLTs) * Adverse events (AEs)/serious adverse events (SAEs) (graded by CTCAE Version 5.0) * Recommended combined dose (RCD) Part B:Confirmed ORR assessed by the Investigator per RECIST 1.1 criteria. Participants will: Part A:Take Capivasertib twice daily from day 1 to 4 of a 7-day cycle, Osimertinib will be given orally QD(once daily) at 80 mg throughout the study treatment period. Part B: Take Osimertinib (80mg QD, continuously) and Capivasertib(RCD,orally BID from day1-day 4 in 7-day cycle , 4 days on /3 days off) till disease progression (PD) or unacceptable toxicity.

NCT Number	NCT07486648
Lead Sponsor	Shanxi Province Cancer Hospital Collaborators: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Conditions	Lung Cancer (NSCLC), Lung Cancer (Non-Small Cell), Advanced Non-small-cell Lung Cancer
Enrollment	53 participants
Start Date	2026-05-15
Primary Completion	2028-10-15 (estimated)
Study Completion	2028-12-31 (estimated)
Updated on ClinicalTrials.gov	2026-03-24