A Study of Osimertinib With or Without Chemotherapy Versus Chemotherapy Alone as Neoadjuvant Therapy for Patients With EGFRm Positive Resectable Non-Small Cell Lung Cancer (NeoADAURA)

• ClinicalTrials.gov Identifier: NCT04351555
• Recruitment Status: Recruiting
• First Posted: April 17, 2020
• Last Update Posted: March 25, 2024
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: April 1, 2020
• First Posted Date: April 17, 2020
• Last Update Posted Date: March 25, 2024
• Actual Study Start Date: December 16, 2020
• Estimated Primary Completion Date: July 5, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 15, 2020)

Major Pathological Response (MPR) [ Time Frame: From date of randomization to an average of 12 weeks after the first dose ]

Defined as ≤10% residual cancer cells in the main tumour, as assessed per central pathology laboratory post-surgery

Original Primary Outcome Measures (submitted: April 15, 2020)

Major Pathological Response (MPR) [ Time Frame: From date of randomization to an average of 12 weeks after the first dose ]

Defined as ≤10% residual cancer cells in the surgical specimen, as assessed per central pathology laboratory post-surgery

Current Secondary Outcome Measures (submitted: November 13, 2023)

• Pathological complete response (pCR) [ Time Frame: From date of randomization to an average of 12 weeks after the first dose ]
  Defined as absence of any viable cancer cells in the dissected tumour samples, including the main tumour, lymph nodes, and margins as assessed per central pathology laboratory post-surgery
• Event-free survival (EFS) [ Time Frame: From date of randomization up to approximately 5.5 years after the last patient is randomized ]
  An event is defined as documented disease progression that precludes surgery or prevents completion of definitive surgery; recurrence or a new lesion, local or distant (a new primary malignancy, confirmed by pathology if clinically feasible, is not considered to be an EFS event); death due to any cause
• Overall Survival (OS) [ Time Frame: From date of randomization up to approximately 5.5 years after the last patient is randomized ]
  OS will be defined as the time from the date of randomisation until death due to any cause
• Disease free survival (DFS) [ Time Frame: From date of randomization up to approximately 5.5 years after the last patient is randomized ]
  DFS is defined as the time from the date of surgery until the first date of disease recurrence (local or distant) or date of death due to any cause, whichever occurs first.
• Downstaging [ Time Frame: From date of randomization to an average of 12 weeks after the first dose ]
  Measured using pathologic mediastinal lymph node evaluation
• Difference between treatment arms in change from baseline in EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 items) [ Time Frame: From date of randomization up to approximately 5.5 years after the last patient is randomized ]
  Assess disease-related symptoms, functioning, and global health status/quality-of-life in patients
• Concordance of EGFRm status between tumour tissue DNA and patient-matched plasma-derived ctDNA [ Time Frame: Baseline ]
• Corcordance of EGFR mutation status between the local and central cobas EGFR mutation test results from baseline tumour samples [ Time Frame: Baseline ]
• PK plasma concentrations of osimertinib [ Time Frame: From the pre-dose of Cycle 2 to post-dose of Cycle 3 (each cycle is 21 days) ]
• Difference between treatment arms in change from baseline in EORTC QLQ-LC13 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 items) [ Time Frame: From date of randomization up to approximately 5.5 years after the last patient is randomized ]
  Assess lung cancer-associated symptoms and side effects from conventional chemotherapy and radiotherapy

Original Secondary Outcome Measures (submitted: April 15, 2020)

• Pathological complete response (pCR) [ Time Frame: From date of randomization to an average of 12 weeks after the first dose ]
  Defined as absence of any residual cancer cells in the surgical specimen assessed post-surgery
• Event-free survival (EFS) [ Time Frame: Up to approximately 21 months after the last patient is randomized ]
  An event is defined as documented disease progression that precludes surgery or requires non-protocol therapy; recurrence or a new lesion, local or distant (a new primary malignancy confirmed by pathology is not considered to be an EFS event.); death due to any cause
• Overall Survival (OS) [ Time Frame: Up to approximately 5.5 years after the last patient is randomized ]
  Patients will be followed up to approximately 5.5 years after they are randomized.
• Disease free survival (DFS) [ Time Frame: From date of randomization up to approximately 15 months after date of resection ]
  DFS is defined as the time from the date of surgery until the first date of disease recurrence (local or distant) or date of death due to any cause, whichever occurs first. If there is residual disease after surgery (eg. positive margins), the DFS event is the date of surgery.
• Downstaging [ Time Frame: From date of randomization to an average of 12 weeks after the first dose ]
  Measured using lymph node staging
• Difference between treatment arms in change from baseline in EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 items) [ Time Frame: From randomization to 24 weeks post-surgery ]
  Assess disease-related symptoms, functioning, and global health status/quality-of-life in patients
• Concordance of EGFRm status between tumour tissue DNA and patient-matched plasma-derived ctDNA [ Time Frame: Baseline ]
• Corcordance of EGFR mutation status between the local and central cobas EGFR mutation test results from baseline tumour samples [ Time Frame: Baseline ]
• PK plasma concentrations of osimertinib [ Time Frame: From the pre-dose of Cycle 2 to post-dose of Cycle 3 (each cycle is 21 days) ]
• Difference between treatment arms in change from baseline in EORTC QLQ-LC13 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 items) [ Time Frame: From randomization to 24 weeks post-surgery ]
  Assess lung cancer-associated symptoms and side effects from conventional chemotherapy and radiotherapy

Current Other Pre-specified Outcome Measures (submitted: November 13, 2023)

• Cure rate [ Time Frame: From the surgery until 5 years after surgery ]
  The cure rate is defined as the percentage of people in this study who are still alive and disease free for a certain period of time after they finished the surgery. Here 5-year landmark cure rate will be calculated in the same time as OS analysis.
• Number of adverse events as assessed by CTCAE 5.0 and other clinical variables for safety and tolerability profile of neoadjuvant osimertinib as monotherapy or in combination with chemotherapy prior to surgery compared with chemotherapy alone [ Time Frame: From the time of enrollment to either 28-days after the last dose of last study treatment for patients who do not undergo surgery, or 90-days post-surgery ]
  Other clinical variables include deaths, laboratory data, vital signs (pulse and BP), ECG, LVEF, ECOG performance status, and ophthalmologic assessment
• MPR using plasma-derived circulating-free tumour DNA (ctDNA) [ Time Frame: From date of randomization to an average of 12 weeks after the first dose ]

Original Other Pre-specified Outcome Measures (submitted: April 15, 2020)

• Cure rate [ Time Frame: From the surgery until five years after surgery ]
  The cure rate is defined as the percentage of people in this study who are still alive and disease free for a certain period of time after they finished the surgery. Here five-year landmark cure rate will be calculated in the same time as OS analysis.
• Number of adverse events as assessed by CTCAE 5.0 and other clinical variables for safety and tolerability profile of neoadjuvant osimertinib as monotherapy or in combination with chemotherapy prior to surgery compared with chemotherapy alone [ Time Frame: From the time of enrollment to either 28-days after the last dose of last study treatment for patients who do not undergo surgery, or 90-days post-surgery ]
  Other clinical variables include deaths, laboratory data, vital signs (pulse and BP), ECG, LVEF, ECOG performance status, and ophthalmologic assessment
• MPR using plasma-derived circulating-free tumour DNA (ctDNA) [ Time Frame: From randomization to week 264 post-surgery ]

Descriptive Information

• Brief Title: A Study of Osimertinib With or Without Chemotherapy Versus Chemotherapy Alone as Neoadjuvant Therapy for Patients With EGFRm Positive Resectable Non-Small Cell Lung Cancer
• Official Title: A Phase III, Randomised, Controlled, Multi-center, 3-Arm Study of Neoadjuvant Osimertinib as Monotherapy or in Combination With Chemotherapy Versus Standard of Care Chemotherapy Alone for the Treatment of Patients With Epidermal Growth Factor Receptor Mutation Positive, Resectable Non-small Cell Lung Cancer
• Brief Summary: This is a Phase III, randomised, controlled, 3-arm, multi-centre study of neoadjuvant osimertinib as monotherapy or in combination with chemotherapy, versus SoC chemotherapy alone, for the treatment of patients with resectable EGFRm Non-Small Cell Lung Cancer
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:

The two arms with SoC chemotherapy (placebo plus chemotherapy versus osimertinib plus chemotherapy) will be double-blinded and placebo-controlled.

Osimertinib monotherapy arm will be open label, sponsor-blind.

Primary Purpose: Treatment

• Condition: Non-Small Cell Lung Cancer

Intervention

• Drug: Osimertinib
  Oral
  Other Name: AZD9291; TAGRISSO
• Drug: Cisplatin
  Cisplatin (75mg/m2) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles.
• Drug: Carboplatin
  Carboplatin (AUC5) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles
• Drug: Placebo
  Oral
• Drug: Pemetrexed
  Pemetrexed (500 mg/m2) to be administered with cisplatin or carboplatin on Day 1 of every 3-week cycle for 3 cycles

Study Arms

• Placebo Comparator: Arm 1: Placebo with platinum-based chemotherapy
  Placebo plus investigator's choice of platinum-based standard of care chemotherapy (pemetrexed/carboplatin or pemetrexed/cisplatin)
  Interventions:

  • Drug: Cisplatin
  • Drug: Carboplatin
  • Drug: Placebo
  • Drug: Pemetrexed
• Experimental: Arm 2: Osimertinib with platinum-based chemotherapy
  Osimertinib 80 mg QD (Dose may be reduced to 40 mg QD at the discretion of the investigator) plus investigator's choice of platinum-based standard of care chemotherapy (pemetrexed/carboplatin or pemetrexed/cisplatin)
  Interventions:

  • Drug: Osimertinib
  • Drug: Cisplatin
  • Drug: Carboplatin
  • Drug: Pemetrexed
• Experimental: Arm 3: Osimertinib monotherapy
  Osimertinib 80 mg QD (Dose may be reduced to 40 mg QD at the discretion of the investigator)
  Intervention: Drug: Osimertinib

• Publications *: Tsuboi M, Weder W, Escriu C, Blakely C, He J, Dacic S, Yatabe Y, Zeng L, Walding A, Chaft JE. Neoadjuvant osimertinib with/without chemotherapy versus chemotherapy alone for EGFR-mutated resectable non-small-cell lung cancer: NeoADAURA. Future Oncol. 2021 Nov;17(31):4045-4055. doi: 10.2217/fon-2021-0549. Epub 2021 Jul 19.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 15, 2020): 328
• Original Estimated Enrollment (submitted: April 15, 2020): 351
• Estimated Study Completion Date: June 13, 2029
• Estimated Primary Completion Date: July 5, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male or female, at least 18 years of age. For patients aged <20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative
• Histologically or cytologically documented non-squamous NSCLC with completely resectable (Stage II - IIIB N2) disease (according to Version 8 of the IASLC Cancer Staging Manual [IASLC Staging Manual in Thoracic Oncology 2016]).
• Complete surgical resection of the primary NSCLC must be deemed achievable, as assessed by a MDT evaluation (which should include a thoracic surgeon, specialised in oncologic procedures).
• Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1 at enrolment, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing
• A tumour which harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations (eg., T790M, G719X, Exon20 insertions, S7681 and L861Q).

Exclusion Criteria:

• Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
• History of another primary malignancy (including any known or suspected synchronous primary lung cancer), except for the following: Malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of investigational product (IP) and of low potential risk for recurrence; Adequately treated non-melanoma skin cancer or lentigo malignancy without evidence of disease; Adequately treated carcinoma in situ without evidence of disease; Any synchronous Stage IA primary lung cancer that is ≤2 cm and planned to be resected during surgery for the Stage II to IIIB N2 lung tumour.
• Patients who have pre-operative radiotherapy treatment as part of their care plan
• Mixed small cell and NSCLC histology
• Stages I, IIIB N3, IIIC, IVA, and IVB NSCLC
• T4 tumours infiltrating the great vessels, the carina, the trachea, the oesophagus, the heart, and/or the vertebral body; and/or any bulky N2 disease.
• Patients who are candidates to undergo only segmentectomies or wedge resections
• Prior treatment with any systemic anti-cancer therapy for NSCLC including chemotherapy, biologic therapy, immunotherapy, or any investigational drug
• Prior treatment with EGFR-TKI therapy
• Current use of (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of cytochrome P450 (CYP) 3A4 (at least 3 weeks prior)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 100 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

Contact: AstraZeneca Cancer Study Locator; 1-877-400-4656; astrazeneca@emergingmed.com

• Listed Location Countries: Austria, Brazil, Bulgaria, Canada, Chile, China, France, Germany, India, Israel, Italy, Japan, Korea, Republic of, Mexico, Peru, Poland, Russian Federation, Singapore, Spain, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States, Vietnam

Administrative Information

• NCT Number: NCT04351555
• Other Study ID Numbers: D516AC00001; 2020-000058-89 ( 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.
• 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 rerefer 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

• Principal Investigator: Jamie Chaft, MD; Memorial Sloan Kettering, USA
• Principal Investigator: Masahiro Tsuboi, MD; National Cancer Center Hospital East, Japan
• Principal Investigator: Walter Weder, MD; Thoraxchirurgie Bethanien, Switzerland

• PRS Account: AstraZeneca
• Verification Date: March 2024