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Osimertinib Plus Capivasertib in NSCLC With PIK3CA/AKT1/PTEN Alterations Following Prior 1L Osimertinib | Clinical Trials | Clareo Health

NOT_YET_RECRUITINGPHASE1/PHASE2

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

The Safety and Efficacy of Osimertinib Plus Capivasertib in EGFRm Advanced Non-small Cell Lung Cancer (NSCLC) Participants With PIK3CA/AKT1/PTEN Alterations Who Had Progressed on First-line Osimertinib Monotherapy or Plus Chemotherapy: a First-in-human, Phase Ib/Ⅱa Study (PRECISION)

NCT07486648•Shanxi Province Cancer Hospital

View on ClinicalTrials.gov

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.

Detailed Description

This is a two-stage study, consisting of Phase Ib dose-escalation, Phase IIa dose expansion. Safety will be intensively monitored in Part A. If RCD (Recommended combined dose) was not reached in Part A, Part B (dose expansion phase) would not be initiated. If RCD was reached in Part A, eligible patients in Part B will be enrolled and receive Osimertinib (80mg QD, continuously) plus 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, with the aim to further evaluate the safety, tolerability and efficacy in terms of ORR, DCR, DOR, PFS and OS. All participants (18 and above) will undergo screening (Day -28 to -1), treatment period (starting from Day 1) and post-intervention follow-up period (end of treatment visit, 30-day safety follow-up and survival follow-up). Dose escalation(Part A) will follow the classic "3+3" schema. The DLT observation period is 28 days post first dose of study treatment. Dose escalation will occur only after DLT observation period is completed for a minimum of 3 participants, relevant data has been reviewed within the Safety Review Committee (SRC), and the SRC approves dose escalation.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Informed consent
•1. Provision of signed and dated, written informed consent form (ICF) prior to any mandatory and non-mandatory study-specific procedures, sampling and analyses
•Age
•2. Male or female age ≥18 years at the time of signing the ICF.
•Type of participant and disease characteristics
•3. Histologically or cytologically confirmed non-squamous locally advanced or metastatic NSCLC which is not amenable to curative therapy.
•4. Documented EGFR sensitive mutations (exon19 deletion, L858R mutation) prior to the first-line EGFR-TKI therapy.
•5. Documented radiologic progression on first-line treatment with Osimertinib monotherapy or Osimertinib plus chemotherapy:
•* Participants treated with Osimertinib in the adjuvant setting can be included if progression occurred \< 6 months after last dose.
•* Participants must be immunotherapy (i.e., programmed cell death protein 1 \[PD-1\] inhibitor, programmed cell death protein 1 ligand 1 \[PD-L1\] inhibitor, Cytotoxic T-lymphocyte associated protein 4 inhibitor) naïve in the metastatic setting.
+34 more criteria

Exclusion Criteria

•Medical conditions
•1. Patients harbouring concurrent actionable driver mutations with locally approved targeted therapies (e.g., MET amplification) will be excluded.
•2. Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
•3. Clinically significant abnormalities of glucose metabolism as defined by any of the following:
•* 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.
•4. 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) .
•• Screening for chronic conditions is not required.
•5. 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.
•6. Any of the following cardiac criteria:
+27 more criteria

Locations (2)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Shanxi Cancer Hospital

Taiyuan, Shanxi, China

Key Dates

Start Date

May 15, 2026

Primary Completion Date

October 15, 2028

Completion Date

December 31, 2028

Last Updated

March 20, 2026

Enrollment

ESTIMATED participants

Conditions

Lung Cancer (NSCLC)Lung Cancer (Non-Small Cell)Advanced Non-small-cell Lung Cancer

Interventions

Capivasertib in combination with Osimertinib

DRUG

Contacts

Jie Wang

CONTACT

139 1070 4669 zlhuxi@163.com

Jinfang Zhai

CONTACT

0351-4866179 tyzlyyll@163.com

Magnetic Resonance Imaging of the Lung: Oncological Applications

NCT07486219

Lung Cancer (NSCLC)

View study

RECRUITINGPHASE3

Sacituzumab Tirumotecan (MK-2870) Versus Pemetrexed and Carboplatin Combination Therapy in Participants With Epidermal Growth Factor (EGFR)-Mutated, Advanced Nonsquamous Non-small Cell Lung Cancer (NSCLC) Who Have Progressed on Prior EGFR Tyrosine Kinase Inhibitors (MK-2870-009)

NCT06305754

Non-small Cell Lung Cancer (NSCLC)

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RECRUITINGNA

Practical Geriatric Assessment in Older Adults With Non-Small Cell Lung Cancer Undergoing Stereotactic Body Radiation Therapy

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 20, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

Magnetic Resonance Imaging of the Lung: Oncological Applications

Sacituzumab Tirumotecan (MK-2870) Versus Pemetrexed and Carboplatin Combination Therapy in Participants With Epidermal Growth Factor (EGFR)-Mutated, Advanced Nonsquamous Non-small Cell Lung Cancer (NSCLC) Who Have Progressed on Prior EGFR Tyrosine Kinase Inhibitors (MK-2870-009)

Practical Geriatric Assessment in Older Adults With Non-Small Cell Lung Cancer Undergoing Stereotactic Body Radiation Therapy

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