A Global Study to Assess the Effects of Osimertinib in Participants With EGFRm Stage IA2-IA3 NSCLC Following Complete Tumour Resection (ADAURA2)

• ClinicalTrials.gov Identifier: NCT05120349
• Recruitment Status: Recruiting
• First Posted: November 15, 2021
• Last Update Posted: April 24, 2024
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: November 3, 2021
• First Posted Date: November 15, 2021
• Last Update Posted Date: April 24, 2024
• Actual Study Start Date: February 21, 2022
• Estimated Primary Completion Date: August 2, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 3, 2021)

Disease-Free Survival (DFS) in high-risk stratum [ Time Frame: From date of randomisation up to approximately 10 years ]

DFS is defined as the time from the date of randomisation until the date of disease recurrence or date of death (by any cause in the absence of recurrence), whichever occurs first. Stratification to the high risk stratum will be based on pathologic features assessed by central pathology review during screening.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 3, 2021)

• Disease-Free Survival (DFS) in overall population [ Time Frame: From date of randomisation up to approximately 10 years ]
  DFS is defined as the time from the date of randomisation until the date of disease recurrence or date of death (by any cause in the absence of recurrence), whichever occurs first.
• Overall Survival (OS) in high-risk stratum and the overall population [ Time Frame: From date of randomization up to approximately 10 years ]
  OS is defined as the time from the date of randomisation until death due to any cause.
• PK plasma concentrations of osimertinib and of metabolite AZ5104 in overall population [ Time Frame: From date of randomisation up to approximately 10 years ]
  Ratio of metabolite-to-osimertinib to be calculated at predose, and at 0.5-2 hours postdose.
• Impact of osimertinib versus placebo on physical functioning [ Time Frame: From date of randomisation up to approximately 10 years ]
  Assess the impact of osimertinib versus placebo on physical functioning in both the high-risk stratum and the overall population as measured by SF-36 V2 health survey
• Central Nervous System (CNS) Disease-Free Survival (DFS) in both the high-risk stratum and the overall population [ Time Frame: From date of randomisation up to approximately 10 years ]
  CNS DFS is defined as the time from randomisation to the time of a CNS lesion (as assessed by investigator) or death due to any cause, regardless of whether the participant withdraws from study intervention or receives other anti-cancer therapy.
• Safety and tolerability in overall population [ Time Frame: From date of randomisation up to approximately 10 years ]
  AEs graded by CTCAE version 5.0

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Global Study to Assess the Effects of Osimertinib in Participants With EGFRm Stage IA2-IA3 NSCLC Following Complete Tumour Resection
• Official Title: A Phase III, Double-blind, Randomised, Placebo-Controlled, International Study to Assess the Efficacy and Safety of Adjuvant Osimertinib Versus Placebo in Participants With EGFR Mutation-positive Stage IA2-IA3 Non-small Cell Lung Cancer, Following Complete Tumour Resection
• Brief Summary: This is a global study to assess the effects of osimertinib in participants with EGFRm stage IA2-IA3 non-small cell lung cancer following complete tumour resection.

Detailed Description

This is a Phase III, double-blind, randomised, placebo-controlled, 2-arm, international study assessing the efficacy and safety of adjuvant osimertinib versus placebo in participants with stage IA2-IA3 EGFRm Non-Small Cell Lung Cancer, who have previously undergone complete tumour resection. All participants must have had a tumour which harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R).

Eligible participants will be randomised in a 1:1 ratio to one of the 2 intervention arms: osimertinib 80 mg or matching placebo, once daily for 3 years unless discontinuation criteria is met.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer

Intervention

• Drug: Osimertinib
  The initial dose of Osimertinib 80mg once daily can be reduced to 40mg once daily. Treatment can continue until disease recurrence, unacceptable toxicity or other discontinuation criteria are met.
  Other Name: AZD9291; TAGRISSO
• Drug: Placebo
  Matching placebo. Initial dose of 80mg once daily can be reduced to 40mg once daily.

Study Arms

• Experimental: Osimertinib
  Osimertinib 80mg, orally, once daily (Dose may be reduced to 40 mg once daily if required at the discretion of the investigator)
  Intervention: Drug: Osimertinib
• Placebo Comparator: Placebo
  Matching placebo for osimertinib, orally, once daily
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 3, 2021): 380
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 1, 2032
• Estimated Primary Completion Date: August 2, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria

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) by cobas® EGFR Mutation Test v2 (Roche Diagnostics) or FoundationOne® test.
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

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: AstraZeneca Clinical Study Information Center; 1-877-240-9479; information.center@astrazeneca.com

• Listed Location Countries: Argentina, Brazil, Canada, China, Germany, Italy, Japan, Korea, Republic of, Malaysia, Poland, Romania, Russian Federation, Singapore, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States, Vietnam
• Removed Location Countries: Ireland

Administrative Information

• NCT Number: NCT05120349
• Other Study ID Numbers: D516FC00001; 2023-509943-28 ( Other Identifier: EU CT Number ); 2021-004135-89 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved, AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Current Responsible Party: AstraZeneca
• Original Responsible Party: Same as current
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jonathan Goldman, MD; UCLA Department of Medicine
• Principal Investigator: Yasuhiro Tsutani, MD, PhD; Kindai University Facility of Medicine
• Principal Investigator: Jie He, MD, PhD; The Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS)

• PRS Account: AstraZeneca
• Verification Date: April 2024