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.
Provision of signed and dated, written informed consent form (ICF) prior to any mandatory and non-mandatory study-specific procedures, sampling and analyses
Male or female age ≥18 years at the time of signing the ICF.
Histologically or cytologically confirmed non-squamous locally advanced or metastatic NSCLC which is not amenable to curative therapy.
Documented EGFR sensitive mutations (exon19 deletion, L858R mutation) prior to the first-line EGFR-TKI therapy.
Patients harbouring concurrent actionable driver mutations with locally approved targeted therapies (e.g., MET amplification) will be excluded.
Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
Fasting glucose ≥7.0 mmol/L (126 mg/dL) or 2 hours after glucose solution intake, blood glucose ≥11.1 mmol/L (200 mg/dL).
HbA1c ≥8.0% (63.9 mmol/mol) at screening. Note: for any patient with evidence of impaired glucose control or insulin resistance refer to the Capivasertib Toxicity Management Guidelines.
Shanxi Province Cancer Hospital
Lead sponsor
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Collaborator