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.
Sequential
Capivasertib in combination with Osimertinib
DrugCapivasertib 320/400 mg(twice daily from day 1 to 4 of a 7-day cycle ),Osimertinib 80 mg(once daily continuously),28 days per cycle
Part A Number of Dose-limiting toxicities (DLTs)
A DLT is defined as any toxicity related to study drug and not attributable to the disease or disease-related processes under investigation, which occurs from the first dose of study treatment (Day 1, Cycle 0) up to the last day of Cycle 1 (28 days after start of dosing)
Part A Adverse events (AEs)/serious adverse events (SAEs) (graded by CTCAE Version 5.0)
Part A Recommended combined dose (RCD)
The RCD is defined as the optimal dose combination of study drugs, established based on integrated assessment of safety and relevant available data from dose escalation phase
Part B Confirmed ORR assessed by the Investigator per RECIST 1.1 criteria
ORR is defined as the percentage of participants who have at least one confirmed response of CR or PR prior to any evidence of progression (as determined by investigator at local site per RECIST 1.1)
Part A Confirmed ORR assessed by the Investigator per RECIST 1.1 criteria
Confirmed ORR as defined in Primary Outcome Measure 4
Part B Progression-free survival(PFS)
PFS is defined as the time from initiation of study treatment to the date of objective disease progression or death (by any cause in the absence of progression), which occurs first, regardless of whether the participant withdraws from therapy or receives another anti-cancer therapy prior to progression
Part B Duration of response(DoR )
DOR will be defined as the time from the date of first documented response (which is subsequently confirmed), until date of documented progression or death in the absence of disease progression
Part B Disease control rate(DCR)
Disease control rate is defined as the proportion of patients with a best overall response of confirmed CR, confirmed PR, or SD
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Shanxi Province Cancer Hospital
Lead sponsor
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
