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Active, not recruiting Phase 3

A Study to Evaluate Chemotherapy Plus Osimertinib Against Chemotherapy Plus Placebo in Patients With Non-small Cell Lung Cancer (NSCLC)

NCT04765059 · tracked via the Priya Life Science USA tracker
Phase
Phase 3
Started
2021-09-12
Last updated
2026-07-07

Condition(s) studied

Non-small Cell Lung Cancer

Investigational drug(s) / intervention(s)

Osimertinib (AZD9291) pemetrexed cisplatin or carboplatin →Placebo for osimertinib (AZD9291) pemetrexed cisplatin or carboplatin

Osimertinib (AZD9291) pemetrexed cisplatin or carboplatin: Randomized patients will receive oral dose of osimertinib with intravenous (IV) pemetrexed plus either IV cisplatin or IV carboplatin

Placebo for osimertinib (AZD9291) pemetrexed cisplatin or carboplatin: Randomized patients will receive oral dose of placebo matching osimertinib with IV pemetrexed plus either IV cisplatin or IV carboplatin

Study summary

The study will evaluate the efficacy and safety of treatment with chemotherapy in combination with osimertinib compared to chemotherapy in combination with placebo in patients whose disease has progressed extracranially following first-line osimertinib treatment.

Eligibility

Sex
ALL
Min age
18 Years
Max age
130 Years
Healthy volunteers
No
Inclusion Criteria: 1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol. 2. Pathologically confirmed non-squamous NSCLC. 3. Locally advanced (clinical stage IIIB or IIIC) or metastatic NSCLC (clinical stage IVA or IVB) or recurrent NSCLC, not amenable to curative surgery or radiotherapy. 4. Evidence of radiological extracranial disease progression following (Investigator-assessed) response or SD for ≥ 6 months during first-line osimertinib treatment, but who have not received further, subsequent treatment. 5. Tumor known to harbor 1 of the 2 or both common epidermal growth factor receptor (EGFR) mutations known to be associated with EGFR tyrosine kinase inhibitor (TKI) sensitivity (Ex19del or L858R), either alone or in combination with other EGFR mutations, which may include T790M. 6. World Health Organization performance status of 0 to 1 at screening with no clinically significant deterioration in the previous 2 weeks. 7. Life expectancy \>12 weeks at Day 1. 8. At least 1 lesion, not previously irradiated, that can be accurately measured. 9. Females must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of childbearing potential, or must have evidence of non-childbearing potential by fulfilling criteria at screening. 10. Male patients must be willing to use barrier contraception Exclusion Criteria: 1. Clinical or radiological evidence of CNS progression on first-line osimertinib. 2. Past medical history of interstitial lung disease (ILD)/pneumonitis, drug-induced ILD/pneumonitis, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD/pneumonitis. 3. Any evidence of severe or uncontrolled systemic diseases. 4. Any of the following cardiac criteria: i) Mean resting QTc \>470 msec ii) Any clinically important abnormalities in rhythm, conduction, or morphology of resting electrocardiogram iii) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events 5. Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of investigational product (IP). 6. Any unresolved toxicities from prior therapy. 7. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of osimertinib. 8. More than 4 weeks elapsed since last dose of osimertinib by date of randomization. 9. Unable to tolerate osimertinib 80 mg first-line therapy. 10. Prior treatment with any systemic anti-cancer therapy. 11. Major surgery within 4 weeks of the first dose of IP. 12. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of IP. 13. Current use of medications or herbal supplements known to be strong inducers of cytochrome P450 (CYP) 3A4. 14. Participation in another clinical study with an IP other than first-line osimertinib during the 4 weeks prior to Day 1.

Primary outcome measure(s)

  • Progression Free Survival (PFS) — From date of first dose (Day 1) until date of progression at local site or death due to any cause or data cut-off date whichever occurred first (up to 3 years 1 month)
    Progression free survival is defined as time from randomization until progression (intracranial or extracranial, whichever occurs first) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (for extracranial progression) and Central nervous system (CNS) RECIST 1.1 (for intracranial progression) as assessed by the Investigator at local site or death due to any cause.

Trial sites (40)

FacilityCityRegionStatus
Research Site Silver Spring Maryland
Research Site Boston Massachusetts
Research Site Beijing China
Research Site Beijing China
Research Site Ganzhou China
Research Site Guangzhou China
Research Site Jinan China
Research Site Shenyang China
Research Site Tianjin China
Research Site Zhengzhou China
Research Site Berlin Germany
Research Site Cologne Germany
Research Site Cologne Germany
Research Site Hanover Germany
Research Site München Germany
Research Site Beersheba Israel
Research Site Jerusalem Israel
Research Site Jerusalem Israel
Research Site Kfar Saba Israel
Research Site Tel Aviv Israel
Research Site Tel HaShomer Israel
Research Site Florence Italy
Research Site Meldola Italy
Research Site Messina Italy
Research Site Naples Italy
Research Site Padova Italy
Research Site Roma Italy
Research Site Terni Italy
Research Site Verona Italy
Research Site Alicante Spain
Research Site Barcelona Spain
Research Site Córdoba Spain
Research Site León Spain
Research Site Madrid Spain
Research Site Málaga Spain
Research Site Murcia Spain
Research Site Oviedo Spain
Research Site Palma de Mallorca Spain
Research Site Seville Spain
Research Site Valencia Spain
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT04765059 on ClinicalTrials.gov ↗ ← All trials in the USA