A Study of Osimertinib with or without Chemotherapy versus Chemotherapy alone as neoadjuvant therapy for Patients with Epidermal Growth Factor Receptor mutation positive resectable Non-Small Cell Lung Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical,Diagnostic,Therapeutic Techniques and Equipment [E]-Surgical Procedures, Operative [E04], Diseases [C] - Hemic and Lymphatic Diseases [C15], Psychiatry and Psychology [F] - Behavioral Disciplines and Activities [F04], Diseases [C] - Neoplasms [C04]

Trial duration

26 Feb 2021 → ongoing

Decision date (initial)

2024-06-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2022-502606-33-00

EudraCT number

2020-000058-89

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacogenetic, Efficacy, Therapy, Diagnosis, Safety, Pharmacoeconomic

To determine the efficacy of osimertinib as monotherapy or in combination with chemotherapy compared to chemotherapy alone, as neoadjuvant treatment

Secondary objectives 6

1. To assess the efficacy of osimertinib as monotherapy or in combination with chemotherapy compared to chemotherapy alone as neoadjuvant treatment, by assessment of pCR, EFS, DFS, downstaging and OS
2. To assess impact of treatment on patients' disease-related symptoms and health-related quality of life
3. To assess the efficacy of osimertinib as monotherapy or in combination with chemotherapy as compared to chemotherapy alone as neoadjuvant treatment, in patients with or without EGFRm detectable at screening in plasma-derived ctDNA
4. To compare the baseline tumour EGFR mutation status in screened patients with evaluable results from baseline plasma samples
5. To compare the local cobas® EGFR Mutation Test v2 and FoundationOne® CDx results used for patient selection with the retrospective central cobas® EGFR Mutation Test v2 results from baseline tumour samples.
6. To characterise the PK of osimertinib and its metabolites

Conditions and MedDRA coding

Patients with histologically or cytologically documented non-squamous NSCLC with completely resectable (Stage II - IIIB N2) disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 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.
2. 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]).
3. Complete surgical resection of the primary NSCLC must be deemed achievable, as assessed by a Mulit-disciplinary Team (MDT) evaluation (which should include a thoracic surgeon, specialised in oncologic procedures).
4. 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.
5. 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 (ie, T790M, G719X, Exon20 insertions, S7681 and L861Q).

Exclusion criteria 10

1. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
2. 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.
3. Patients who have pre-operative radiotherapy treatment as part of their care plan
4. Mixed small cell and NSCLC histology
5. Stages I, IIIB N3, IIIC, IVA, and IVB NSCLC
6. 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.
7. Patients who are candidates to undergo only segmentectomies or wedge resections
8. Prior treatment with any systemic anti-cancer therapy for NSCLC including chemotherapy, biologic therapy, immunotherapy, or any investigational drug
9. Prior treatment with EGFR-TKI therapy
10. 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)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Major Pathological Response (MPR) (≤10% residual cancer cells in the main tumour, as assessed per central pathology laboratory post surgery)

Secondary endpoints 5

1. Complete pathological Response (pCR) (absence of any residual cancer cells in the dissected tumour samples, including the main tumour and lymph nodes, assessed post-surgery); EFS; DFS; Downstaging; Overall Survival (OS)
2. Change from baseline in Patient reported outcomes (ePRO)
3. Concordance of EGFRm status between tumour tissue DNA and patientmatched plasma-derived ctDNA
4. Concordance of EGFR mutation status between the local and central cobas EGFR mutation test results from baseline tumour samples.
5. PK plasma concentrations of osimertinib

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

7 EU/EEA countries · 19 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 54 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications