Phase II AZD9291 Open Label Study in NSCLC After Previous EGFR TKI Therapy in EGFR and T790M Mutation Positive Tumours (AURA2)

• ClinicalTrials.gov Identifier: NCT02094261
• Recruitment Status: Completed
• First Posted: March 21, 2014
• Results First Posted: June 7, 2016
• Last Update Posted: December 11, 2023
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

A Phase II, Open Label, Single-arm Study to Assess the Safety and Efficacy of AZD9291 in Patients with Locally Advanced/Metastatic Non Small Cell Lung Cancer whose Disease has Progressed with Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and whose Tumours are Epidermal Growth Factor Receptor Mutation and T790M Mutation Positive

Condition or disease	Intervention/treatment	Phase
Non Small Cell Lung Cancer	Drug: AZD9291	Phase 2

Detailed Description:

This is a phase II, open label, single arm study assessing the safety and efficacy of AZD9291 (80 mg, orally, once daily) in patients with a confirmed diagnosis of Epidermal Growth Factor Receptor mutation positive and T790M mutation positive NSCLC,who have progressed following prior therapy with an approved Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) agent. Patients must agree to provide a biopsy for central confirmation of T790M mutation status following confirmed disease progression on the most recent treatment regimen. The primary objective of the study is to assess the efficacy of AZD9291 by assessment of Objective Response Rate according to RECIST 1.1 by an Independent Central Review.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 210 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II, Open Label, Single-arm Study to Assess Safety and Efficacy of AZD9291 in Patients With Locally Advanced/Metastatic NSCLC Whose Disease Has Progressed With Previous EGFR TKI and Whose Tumours Are EGFR and T790M Mutation Positive
• Actual Study Start Date: May 20, 2014
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: November 7, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: AZD9291; Once daily tablet 80 mg	Drug: AZD9291; Once daily tablet 80 mg

Outcome Measures

Primary Outcome Measures :

1. Objective Response Rate (ORR) [ Time Frame: RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis) ]
   Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. ORR is the percentage of patients with at least 1 visit response of CR or PR (according to independent review) that was confirmed at least 4 weeks later, prior to progression or further anti-cancer therapy.

Secondary Outcome Measures :

1. Duration of Response (DoR) [ Time Frame: RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis) ]
   Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. DoR was defined as the time from the date of first documented response (CR or PR that was subsequently confirmed) until the date of documented progression (PD) or death in the absence of disease progression (by investigator assessment).
2. Disease Control Rate (DCR) [ Time Frame: RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis) ]
   Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions; Stable disease (SD): Neither sufficient shrinkage to qualify as a response nor sufficient growth to qualify as progression; Progressive Disease (PD): >= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. DCR is the percentage of patients with best response of CR, PR or SD (according to independent review), prior to progression (PD) or further anti-cancer therapy.
3. Progression-Free Survival (PFS) [ Time Frame: RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis) ]
   Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Progressive Disease (PD): >= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. PFS is the time from date of first dose until the date of PD (by independent review) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from AZD9291 therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST 1.1 assessment.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 130 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion:

• Aged at least 18 years. Japan patients aged at least 20 years.
• Locally advanced/metastatic NSCLC not amenable to curative surgery or radiotherapy
• Radiological documentation of disease progression:

following 1st line EGFR TKI treatment but who have not received further treatment OR following prior therapy with an EGFR TKI and a platinum-based doublet chemotherapy. Patients who received prior EGFR TKI and platinum-based doublet chemotherapy may have also received additional lines of treatment. All patients must have documented radiological progression on the last treatment administered prior to enrolling in the study.

• Disease progression following 1st line EGFR TKI treatment or following prior EGFR TKI and platinum-containing doublet chemotherapy.
• Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q). Patients must have central confirmation of tumour T790M mutation positive status from a biopsy sample taken after confirmation of disease progression on the most recent treatment regimen.
• World Health Organisation (WHO) performance status 0-1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks.
• At least one lesion, not previously irradiated and not chosen for biopsy during the study screening period, that can be accurately measured at baseline as ≥ 10mm in the longest diameter (except lymph nodes which must have short axis ≥ 15mm) with computerised tomography (CT) or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements.
• Females of child-bearing potential using contraception; negative pregnancy test.

Exclusion:

• Treatment with an EGFR-TKI within 8 days of study entry; any cytotoxic chemotherapy, investigational agents or other anticancer drugs within 14 days of study entry; previous treatment with AZD9291 (or 3rd generation TKIs); major surgery within 4 weeks; radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks; current treatment with potent inhibitors of CYP2C8 and potent inhibitors/inducers of CYP3A4.
• Unresolved toxicities from prior therapy.
• Unstable spinal cord compression/brain metastases.
• Severe/uncontrolled systemic diseases, including uncontrolled hypertension, bleeding diatheses or infection.
• Refractory nausea/vomiting, chronic gastrointestinal diseases or bowel resection.
• Cardiac disease.
• Past history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
• Inadequate bone marrow reserve or organ function.

Contacts and Locations

Locations

United States, California

Research Site

La Jolla, California, United States, 92093

Research Site

Orange, California, United States, 92868

United States, Connecticut

Research Site

New Haven, Connecticut, United States, 06510

Research Site

Norwalk, Connecticut, United States, 06850

United States, Indiana

Research Site

Indianapolis, Indiana, United States, 46202

United States, Massachusetts

Research Site

Boston, Massachusetts, United States, 02215

United States, New Hampshire

Research Site

Lebanon, New Hampshire, United States, 03756

United States, New York

Research Site

New York, New York, United States, 10032

United States, North Carolina

Research Site

Durham, North Carolina, United States, 27710

Canada, Alberta

Research Site

Edmonton, Alberta, Canada, T6G 1Z2

Canada, Ontario

Research Site

Ottawa, Ontario, Canada, K1H 8L6

Research Site

Toronto, Ontario, Canada, M5G 2M9

Hong Kong

Research Site

Hong Kong, Hong Kong

Research Site

Shatin, Hong Kong, 00000

Italy

Research Site

Milano, Italy, 20132

Research Site

Milan, Italy, 20141

Research Site

Napoli, Italy, 80131

Research Site

Perugia, Italy, 06132

Research Site

Verona, Italy, 37134

Japan

Research Site

Akashi-shi, Japan, 673-8558

Research Site

Chuo-ku, Japan, 104-0045

Research Site

Kitaadachi-gun, Japan, 362-0806

Research Site

Kitakyushu-shi, Japan, 802-0077

Research Site

Koto-ku, Japan, 135-8550

Research Site

Nagoya-shi, Japan, 460-0001

Research Site

Nagoya-shi, Japan, 464-8681

Research Site

Niigata-shi, Japan, 951-8566

Research Site

Osaka-shi, Japan, 534-0021

Research Site

Osaka-shi, Japan, 541-8567

Research Site

Osakasayama, Japan, 589-8511

Research Site

Sakai-shi, Japan, 591-8555

Research Site

Wakayama-shi, Japan, 641-8510

Research Site

Yokohama-shi, Japan, 236-0051

Korea, Republic of

Research Site

Goyang-si, Korea, Republic of, 10408

Research Site

Seongnam-si, Korea, Republic of, 13620

Research Site

Seoul, Korea, Republic of, 06591

Spain

Research Site

A Coruña, Spain, 15006

Research Site

Barcelona, Spain, 08025

Research Site

Madrid, Spain, 28007

Research Site

Majadahonda, Spain, 28222

Research Site

Málaga, Spain, 29010

Research Site

Valencia, Spain, 46026

Taiwan

Research Site

Taichung, Taiwan, 40705

Research Site

Taipei, Taiwan, 112

Sponsors and Collaborators

AstraZeneca

Investigators

• Principal Investigator: Glenwood Goss, MD; 501 Smyth Road, Ottawa, Canada
• Principal Investigator: Tetsuya Mitsudomi, MD; Kinki University Hospital, Faculty of Medicine, Osaka, Japan

More Information

Additional Information:

D5160C00002_12_1_01csp_andamendments-redaction_proposal_Redacted1 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ahn MJ, Han JY, Kim DW, Cho BC, Kang JH, Kim SW, Yang JC, Mitsudomi T, Lee JS. Osimertinib in Patients with T790M-Positive Advanced Non-small Cell Lung Cancer: Korean Subgroup Analysis from Phase II Studies. Cancer Res Treat. 2020 Jan;52(1):284-291. doi: 10.4143/crt.2019.200. Epub 2019 Jul 23.

Ahn MJ, Tsai CM, Shepherd FA, Bazhenova L, Sequist LV, Hida T, Yang JCH, Ramalingam SS, Mitsudomi T, Janne PA, Mann H, Cantarini M, Goss G. Osimertinib in patients with T790M mutation-positive, advanced non-small cell lung cancer: Long-term follow-up from a pooled analysis of 2 phase 2 studies. Cancer. 2019 Mar 15;125(6):892-901. doi: 10.1002/cncr.31891. Epub 2018 Dec 4.

Goss G, Tsai CM, Shepherd FA, Ahn MJ, Bazhenova L, Crino L, de Marinis F, Felip E, Morabito A, Hodge R, Cantarini M, Johnson M, Mitsudomi T, Janne PA, Yang JC. CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials. Ann Oncol. 2018 Mar 1;29(3):687-693. doi: 10.1093/annonc/mdx820.

Goss G, Tsai CM, Shepherd FA, Bazhenova L, Lee JS, Chang GC, Crino L, Satouchi M, Chu Q, Hida T, Han JY, Juan O, Dunphy F, Nishio M, Kang JH, Majem M, Mann H, Cantarini M, Ghiorghiu S, Mitsudomi T. Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2016 Dec;17(12):1643-1652. doi: 10.1016/S1470-2045(16)30508-3. Epub 2016 Oct 14.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT02094261
• Other Study ID Numbers: D5160C00002; 2014-000531-17 ( EudraCT Number )
• First Posted: March 21, 2014
• Results First Posted: June 7, 2016
• Last Update Posted: December 11, 2023
• Last Verified: December 2023

Individual Participant Data (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; 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

Keywords provided by AstraZeneca:

Phase II, open label study; safety and efficacy of AZD9291; diagnosis of Epidermal Growth Factor Receptor mutation positive and T790M mutation positive NSCLC

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Osimertinib; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents