A Study of 5 Years of Adjuvant Osimertinib in Completely Resected Epidermal Growth Factor Receptor Mutation (EGFRm) Non-small Cell Lung Carcinoma (NSCLC) (TARGET)

• ClinicalTrials.gov Identifier: NCT05526755
• Recruitment Status: Recruiting
• First Posted: September 2, 2022
• Last Update Posted: May 16, 2024
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: September 1, 2022
• First Posted Date: September 2, 2022
• Last Update Posted Date: May 16, 2024
• Actual Study Start Date: March 6, 2023
• Estimated Primary Completion Date: April 5, 2029 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 1, 2022)

Assess the Efficacy of Osimertinib as Measured by Disease Free Survival (DFS) [Common EGFRm Cohort]. [ Time Frame: From date of first dose until date of disease recurrence or death (by any cause in the absence of recurrence), up to approximately 5 years. Assessed at 5 years. ]

Defined as time from date of first dose until disease recurrence, or death due to any cause in the absence of recurrence.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 1, 2022)

• Disease Free Survival Rate at 3, 4 and 5 Years (Uncommon EGFRm Cohort) [ Time Frame: From date of first dose until date of disease recurrence or death (by any cause in the absence of recurrence), up to approximately 5 years. Assessed at 3 years, 4 years, and 5 years. ]
  Defined as the proportion of participants alive and disease free at 3, 4, and 5 years.
• DFS Rate at 3 and 4 Years (Common EGFRm Cohort) [ Time Frame: From date of first dose until date of disease recurrence or death (by any cause in the absence of recurrence), up to approximately 5 years. Assessed at 3 years, and 4 years. ]
  Defined as the proportion of participants alive and disease free at 3, and 4 years.
• Overall Survival (OS) [Common EGFRm Cohort] [ Time Frame: From date of first dose until the date of death due to any cause, up to approximately 5 years. Assessed at 3 years, 4 years, and 5 years. ]
  Defined as time from date of first dose until the date of death due to any cause.
• Safety and tolerability in overall population (Common EGFRm Cohort and Uncommon EGFRm Cohort) [ Time Frame: From date of first dose up to approximately 5 years ]
  Adverse Events (AEs) graded by CTCAE version 5.0.
• Recurrence events in overall population (Common EGFRm Cohort and Uncommon EGFRm Cohort) [ Time Frame: From date of first dose up to approximately 5 years ]
  Local/regional, or distant recurrence events assessed.

• 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 Study of 5 Years of Adjuvant Osimertinib in Completely Resected Epidermal Growth Factor Receptor Mutation (EGFRm) Non-small Cell Lung Carcinoma (NSCLC)
• Official Title: An Open-label, Single-arm, Phase II, Multinational, Multicentre Study to Assess the Efficacy and Safety of 5 Years of Osimertinib in Participants With EGFRm-positive Stage II-IIIB NSCLC, Following Complete Tumour Resection With or Without Adjuvant Chemotherapy
• Brief Summary: To assess the efficacy and safety of osimertinib in participants with EGFRm positive stage II-IIIB NSCLC, following complete tumour resection with or without adjuvant chemotherapy.
• Detailed Description: This is a phase 2 open-label study to assess the efficacy and safety of osimertinib in participants with stage II-IIIB NSCLC with sensitising EGFR mutations. The study is designed to evaluate 5 years of adjuvant osimertinib therapy.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Stage II-IIIB Non-small Cell Lung Carcinoma

Intervention

Drug: Osimertinib 80 mg/40 mg

Participants will receive osimertinib (80 mg or 40 mg orally, once daily).

Other Name: AZD9291

Study Arms

Experimental: Osimertinib

Participants will receive osimertinib (AZD9291).

Intervention: Drug: Osimertinib 80 mg/40 mg

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 1, 2022): 180
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 5, 2029
• Estimated Primary Completion Date: April 5, 2029 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Male or female aged at least 18 years.
2. Histologically confirmed diagnosis of primary NSCLC on predominantly non-squamous histology.
3. Magnetic Resonance Imaging (MRI) or contrast computed tomography (CT) scan of the brain.
4. Participants must be classified post-operatively as Stage II, IIIA, or IIIB on the basis of surgical pathologic criteria.
5. Confirmation by the local laboratory that the tumour harbours one of the two common EGFR mutations (Ex19del, L858R), either alone or in combination with other EGFR mutations including de novo EGFR mutation resulting in substitution of threonine with methionine at amino acid position 790 in exon 20 of EGFR (T790M) or uncommon EGFR mutations G719X, S768I, and L861Q, either alone, in combination with each other, or in combination with other uncommon EGFR mutations (excluding all exon 20 insertions) (Uncommon EGFRm Cohort).
6. Complete surgical resection of the primary NSCLC is mandatory. All gross disease must have been removed at the end of surgery. All surgical margins of resection must be negative for tumour.
7. Complete recovery from surgery and standard post-operative therapy (if applicable) at start of study intervention.
8. World Health Organisation Performance Status of 0 to 1.
9. Female participants must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of childbearing potential.
10. Male participants must use effective barrier contraception.

Exclusion Criteria:

1. Major surgery (including primary tumour surgery, excluding placement of vascular access) within 4 weeks prior to the first dose of study drug.
2. Participants currently receiving medications or herbal supplements known to be potent inducers of CYP3A4 (at least 3 weeks prior to first dose).
3. Participants who have had only segmentectomies or wedge resections.
4. History of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer, or other solid tumours curatively treated with no evidence of disease for > 5 years following the end of study intervention.

5. Treatment with any of the following:

   • Pre-operative or post-operative or planned radiation therapy for the current lung cancer.
   • Pre-operative (neo-adjuvant) platinum-based or other chemotherapy.
   • Any prior anticancer or immunological therapy, including investigational therapy, for treatment of NSCLC other than standard platinum-based doublet post-operative adjuvant chemotherapy.
   • Prior treatment with neoadjuvant or adjuvant EGFR tyrosine kinase inhibitor (TKI).
6. 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.

7. Any of the following cardiac criteria:

   • Mean resting corrected QT (QTc) interval > 470 msec, obtained from 3 electrocardiograms (ECGs).
   • Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.
   • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events.
   • Heart failure, congenital long QT interval (QT) syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes (TdP).
8. Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD.
9. Inadequate bone marrow reserve or organ function.
10. Women who are breastfeeding.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 130 Years (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: Hong Kong, Italy, Korea, Republic of, Malaysia, Philippines, Singapore, Spain, Taiwan, Thailand, United Kingdom, United States

Administrative Information

• NCT Number: NCT05526755
• Other Study ID Numbers: D5162C00048; 2021-003024-33 ( EudraCT Number )
• Has Data Monitoring Committee: No

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 participant-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• 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 at 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: Not Provided
• PRS Account: AstraZeneca
• Verification Date: May 2024