Osimertinib Plus Capivasertib in NSCLC With PIK3CA/AKT1/PTEN Alterations Following Prior 1L Osime… (NCT07486648) | Clinical Trial Compass
Not Yet RecruitingPhase 1/2
Osimertinib Plus Capivasertib in NSCLC With PIK3CA/AKT1/PTEN Alterations Following Prior 1L Osimertinib
China53 participantsStarted 2026-05-15
Plain-language summary
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.
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. 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.
✓. Documented radiologic progression on first-line treatment with Osimertinib monotherapy or Osimertinib plus chemotherapy:
✓. Mandatory provision of the required number of FFPE tumour tissue samples for PIK3CA mutations and/or AKT1 mutations and/or PTEN loss-of-function (LOF) mutations testing, which fulfils the following requirements:
✓. At least one lesion, not previously irradiated, not biopsied during the screening period, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with CT or MRI, which is suitable for accurate repeated measurements. If only one measurable lesion exists, it is acceptable to be used if baseline tumour assessment scans are done at least 14 days after the screening tumour specimen collection is performed.
What they're measuring
1
Part A Number of Dose-limiting toxicities (DLTs)
Timeframe: 28 days post first dose of study treatment
2
Part A Adverse events (AEs)/serious adverse events (SAEs) (graded by CTCAE Version 5.0)
Timeframe: From the time of signature of informed consent form up to 44 months
3
Part A Recommended combined dose (RCD)
Timeframe: From first dose of study treatment up to 12 months
4
Part B Confirmed ORR assessed by the Investigator per RECIST 1.1 criteria
Timeframe: 5 months post first dose of study treatment
. Adequate bone marrow reserve and organ function as follows:
Exclusion criteria
✕. 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.
✕. Clinically significant abnormalities of glucose metabolism as defined by any of the following:
✕. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol, or active infection (e.g. patients receiving treatment for infection) including hepatitis C and human immunodeficiency virus (HIV), or active uncontrolled hepatitis B virus (HBV) infection, or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice) .
✕. Spinal cord compression, leptomeningeal metastasis, or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention.
✕. Any of the following cardiac criteria:
✕. History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥2 years before the first dose of investigational product (IP) and of low potential risk for recurrence. Exceptions include adequately resected non-melanoma skin cancer and curatively treated in situ disease.
✕. Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment except for alopecia and grade 2 prior platinum-therapy related neuropathy. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention in the opinion of the Investigator may be included (e.g., hearing loss).