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NCT Number: NCT04351555

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

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

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Non-small Cell Lung Cancer Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year–100 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Research Site, Graz, Austria

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Osimertinib

Drug

Oral

Other names: AZD9291; TAGRISSO

Cisplatin

Drug

Cisplatin (75mg/m2) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles.

carboplatin

Drug

Carboplatin (AUC5) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles

Placebo

Drug

Oral

Pemetrexed

Drug

Pemetrexed (500 mg/m2) to be administered with cisplatin or carboplatin on Day 1 of every 3-week cycle for 3 cycles

Primary outcomes

  1. Major Pathological Response (MPR) - IASLC Method

    Time frame: From date of randomization to an average of 12 weeks after the first dose

    Defined as ≤10% viable cancer cells in the surgical specimen, as assessed per central pathology laboratory post-surgery (IASLC method). Patients will only be considered to have an MPR if they also have an R0 margin result.

  2. Major Pathological Response (MPR) - Chemotherapy Method

    Time frame: From date of randomization to an average of 12 weeks after the first dose

    Defined as ≤10% viable cancer cells in the surgical specimen, as assessed per central pathology laboratory post-surgery (chemotherapy method). Patients will only be considered to have an MPR if they also have an R0 margin result.

Secondary outcomes

  1. Pathological Complete Response (pCR) - IASLC Method

    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 using IASLC method. Patients will only be considered to have pCR if they also have an R0 margin result based on site assessment.

  2. Pathological Complete Response (pCR) - Chemotherapy Method

    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 using chemotherapy method. Patients will only be considered to have pCR if they also have an R0 margin result based on site assessment.

  3. Downstaging

    Time frame: From date of randomization to an average of 12 weeks after the first dose.

    Measured using pathologic mediastinal lymph node evaluation. Pathological downstaging is defined as baseline N2 patients becoming N1/N0 or N1 to N0 at the time of surgery. Only patients with pathological staging at both baseline and surgery are included in this analysis.

  4. Concordance of EGFRm Status Between Tumor Tissue DNA and Patient-matched Plasma-derived ctDNA (Mutation Ex19Del or L858R)

    Time frame: Screening/Baseline

    Comparing the baseline central cobas® EGFR Mutation Test V2 between tumor tissue DNA and matched plasma ctDNA results (excluding invalid results). Since this endpoint uses pre-randomization data, treatment arms were combined for the analysis.

  5. Concordance of EGFR Mutation Status Between the Local and Central Test Results From Baseline Tumor Samples (Mutation Ex19Del or L858R)

    Time frame: Screening/Baseline

    Comparing the local EGFR mutation test result used for patient selection with the retrospective baseline central cobas® EGFR Mutation Test V2 results (excluding invalid results). Since this endpoint uses pre-randomization data, treatment arms were combined for the analysis.

  6. Change From Baseline in EORTC QLQ-C30 Primary Subscale Scores (Neoadjuvant Period)

    Time frame: Assessed at baseline, Cycle 2 Day1, Cycle 3 Day1, and Pre-surgical assessment (on D64, -1 to +21 days ).

    Average change from baseline across all visits are reported. The analysis was performed using a MMRM analysis on the change from baseline in the score at each visit, including subject (random effect), treatment, visit (fixed effect & repeated measure) and treatment by visit interaction as explanatory variables, with the baseline score as a covariate along with the baseline score by assessment interaction. EORTC QLQ-C30 has 30 questions and questions are combined to produce symptom scales, individual symptom items, functional scales, and global health status (GHS)/quality of life (QoL). Each of the scale/items range from 0-100 after a linear transformation. Positive change from baseline scores on the GHS/QoL and functioning scales indicate improvement on health status/function, and negative change scores on symptom scales/items represent less symptom severity/improvement on symptom status.

  7. Change From Baseline in EORTC QLQ-LC13 Primary Subscale Scores (Neoadjuvant Period)

    Time frame: Assessed at baseline, Cycle 2 Day1, Cycle 3 Day1, and Pre-surgical assessment (on D64, -1 to +21 days).

    Average change from baseline across all visits are reported. The analysis was performed using a MMRM analysis on the change from baseline in the score at each visit, including subject (as a random effect), treatment, visit (as fixed effect and repeated measure) and treatment by visit interaction as explanatory variables, with the baseline score as a covariate along with the baseline score by assessment interaction. EORTC QLQ-LC13 has 13 questions and scores range from 0-100 after a linear transformation. Questions assess cough, hemoptysis, dyspnea, site specific pain, sore mouth, dysphagia, peripheral neuropathy, and alopecia and pain medication. While the QLQ-LC13 includes more scales, only the Coughing, Pain in chest, and Dyspnea subscale scores were analyzed for this endpoint.

    Negative change from baseline scores indicates less symptom severity, and thus improvement on health status.

  8. 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)

    Summary of plasma concentrations (nM) of Osimertinib

  9. PK Plasma Concentrations of AZ5104

    Time frame: From the pre-dose of Cycle 2 to post-dose of Cycle 3 (each cycle is 21 days)

    Summary of plasma concentrations (nM) of AZ5104

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study 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

Acronym: NeoADAURA

Important dates

Study start
2020
Primary completion
2024
Study completion
2029
First posted
Apr 17, 2020
Registry last updated
Jun 5, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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