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

• Status: Recruiting
• Trial end date: 2024-12-30
• Target enrollment: 0
• Participant gender: All

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 who have progressed extracranially following first-line osimertinib treatment.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AstraZeneca
• Collaborator: Parexel
• Treatments: Carboplatin; Cisplatin; Osimertinib; Pemetrexed

Criteria

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 response with first-line osimertinib treatment but who have not received further, subsequent treatment.

5. World Health Organization performance status of 0 to 1 at screening with no clinically significant deterioration in the previous 2 weeks.

6. Life expectancy >12 weeks at Day 1.

7. At least 1 lesion, not previously irradiated.

8. Females must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of child-bearing potential, or must have evidence of non-child-bearing potential by fulfilling criteria at screening.

9. 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 ILD (interstitial lung disease)/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 extracranial 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 extracranial 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.