A late stage clinical trial to investigate the efficacy and safety of Osimertinib versus Placebo in patients with stage IA2-IA3 non-small cell lung cancer, following complete tumour resection.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 May 2022 → ongoing

Decision date (initial)

2024-09-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2023-509943-28-00

EudraCT number

2021-004135-89

ClinicalTrials.gov

NCT05120349

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess the efficacy of osimertinib compared to placebo as measured by disease-free survival in participants in the high-risk stratum.

Secondary objectives 6

1. To demonstrate the effectiveness of osimertinib versus placebo by assessment of disease-free survival (DFS) in the overall population.
2. To demonstrate the effectiveness of osimertinib versus placebo by assessment of overall survival (OS) in participants in both the high-risk stratum and the overall population.
3. To assess the impact of osimertinib versus placebo on physical functioning in both the high-risk stratum and overall population.
4. To assess the effectiveness of osimertinib versus placebo by assessment of central nervous system disease free survival (DFS) in both the high-risk stratum and the overall population.
5. To characterise the pharmacokinetics of osimertinib and its metabolites (AZ13575104 [AZ5104]) in the overall population.
6. To assess the safety and tolerability profile of osimertinib versus placebo in the overall population.

Conditions and MedDRA coding

Stage IA2-IA3 non-small cell lung carcinoma, with EGFR mutation type (Ex19del, L858R), following complete tumour resection.

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Male or female, at least ≥ 18 years.
2. NSCLC, of non-squamous histology.
3. Stage IA2 or IA3 disease, based on TNM8 classification.
4. Complete surgical resection (R0) of the primary NSCLC by lobectomy, bilobectomy, segmentectomy or sleeve resection.
5. Complete recovery from surgery at the time of randomisation. Study intervention cannot commence within 4 weeks following surgery. No more than 12 weeks may have elapsed between surgery and randomisation for participants.
6. World Health Organization performance status of 0 or 1.
7. Provision of tumour sample for central pathology assessment of pathologic risk factors and to assess EGFR mutation status prior to randomisation.
8. A tumour which harbours one of the 2 EGFR mutations (Ex19del, L858R).
9. Minimum life expectancy of > 6 months.
10. 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. Male subjects must be willing to use barrier contraception.

Exclusion criteria 11

1. Mixed small cell and non-small cell cancer history.
2. Participants with incomplete (R1/R2) resection, or who have undergone pneumonectomy or only wedge resection.
3. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including HCV and HIV or active uncontrolled HBV infection.
4. History of another primary malignancy, including any known or suspected synchronous primary lung cancer, except for malignancy treated with curative intent with no known active disease ≥ 5 years before the first dose of study intervention and of low potential risk for recurrence.
5. Any of the following cardiac criteria: Mean resting QTcF interval > 470 ms, obtained from triplicate ECGs performed at screening / Any abnormalities in rhythm, conduction, or morphology of resting ECG / Any factors that increase the risk of QTcF prolongation or risk of arrhythmic events.
6. History of interstitial lung disease.
7. Inadequate bone marrow reserve or organ function.
8. Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study intervention.
9. Prior treatment with any anticancer therapy for NSCLC (including chemotherapy, radiotherapy, immunotherapy, and EGFR-TKIs).
10. Major surgery or significant traumatic injury within 4 weeks of the first dose of study intervention.
11. Participants currently receiving medications or herbal supplements known to be strong inducers of CYP3A4.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease free survival (DFS) in the high-risk stratum by investigators' assessment.

Secondary endpoints 7

1. Disease free survival (DFS) in the overall population by investigator's assessment.
2. Disease free survival (DFS) in both the high-risk stratum and overall population.
3. Overall survival (OS) in participants in both the high-risk stratum and overall population.
4. Impact of osimertinib versus placebo on physical functioning in both the high-risk stratum and overall population.
5. Effectiveness of osimertinib versus placebo by assessment of central nervous system disease free survival (DFS) in both the high-risk stratum and the overall population.
6. Characterise the pharmacokinetics of osimertinib and its metabolites (AZ13575104 [AZ5104]) in the overall population.
7. Safety and tolerability profile of osimertinib versus placebo in the overall population.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

5 EU/EEA countries · 29 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 25 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications