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

Study identifier:D516AC00001

ClinicalTrials.gov identifier:NCT04351555

EudraCT identifier:2020-000058-89

CTIS identifier:N/A

Recruiting

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

Medical condition

Non-small Cell Lung Cancer

Phase

Phase 3

Healthy volunteers

Study drug

Osimertinib, Cisplatin, Carboplatin, Placebo, Pemetrexed

Sex

All

Estimated Enrollment

328

Study type

Interventional

Age

18 Years - 100 Years

Date

Study Start Date: 16 Dec 2020

Estimated Primary Completion Date: 05 Jul 2024

Estimated Study Completion Date: 13 Jun 2029

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2024 by AstraZeneca

Collaborators

Inclusion and exclusion 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)

Sort by status

No locations available

Arms	Assigned Interventions
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)	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
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)	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: Pemetrexed Pemetrexed (500 mg/m2) to be administered with cisplatin or carboplatin on Day 1 of every 3-week cycle for 3 cycles
Experimental: Arm 3: Osimertinib monotherapy Osimertinib 80 mg QD (Dose may be reduced to 40 mg QD at the discretion of the investigator)	Drug: Osimertinib Oral Other Name: AZD9291; TAGRISSO

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Contact Backup

AstraZeneca Cancer Study Locator

1-877-400-4656