Phase II Single Arm Study of AZD9291 to Treat NSCLC Patients in Asia Pacific (AURA17)

A Phase II, Open Label, Single-arm Study to Assess the Safety and Efficacy of AZD9291 in Asia Pacific 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 Harbour a T790M Mutation Within the Epidermal Growth Factor Receptor Gene.

A Phase II, Open Label, Single-arm Study to Assess the Safety and Efficacy of AZD9291 in Asia Pacific 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 harbour a T790M mutation within the Epidermal Growth Factor Receptor Gene

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: AZD9291

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 Asia Pacific patients with a confirmed diagnosis of Epidermal Growth Factor Receptor (EGFR) sensitising mutation positive (ie, G719X, exon 19 deletion, L858R, L861Q) and T790M mutation positive (hereafter referred to as EGFRm+ and T790M+) un-resectable, locally advanced or metastatic NSCLC (Stage IIIB-IV), who have progressed on an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor(EGFR-TKI), either as first line treatment or following one line of EGFR-TKI and one line of platinum containing doublet chemotherapy. 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 Type: Interventional
• Enrollment (Actual): 171
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Kogarah, Australia, 2217
    • Research Site
  • Nedlands, Australia, 6009
    • Research Site
  • Woolloongabba, Australia, 4102
    • Research Site
• China
  • Beijing, China, 100142
    • Research Site
  • Beijing, China, 100021
    • Research Site
  • Beijing, China, 100730
    • Research Site
  • Changchun, China, 130000
    • Research Site
  • Chengdu, China, 610041
    • Research Site
  • Chongqing, China, 400038
    • Research Site
  • Chongqing, China, 400042
    • Research Site
  • Fuzhou, China, 350014
    • Research Site
  • Haikou, China, 570311
    • Research Site
  • Hangzhou, China, 310006
    • Research Site
  • Hangzhou, China, 310022
    • Research Site
  • Hangzhou, China, 310003
    • Research Site
  • Harbin, China, 150049
    • Research Site
  • Jinan, China, 2501117
    • Research Site
  • Nanjing, China, 210009
    • Research Site
  • Shanghai, China, 200032
    • Research Site
  • Shanghai, China, 200030
    • Research Site
  • Shanghai, China, CN-200433
    • Research Site
  • Wuhan, China, 430022
    • Research Site
  • Wuhan, China, 430030
    • Research Site
  • Xi'an, China, 710032
    • Research Site
  • Xi'an, China, 710038
    • Research Site
  • Zhengzhou, China, 450008
    • Research Site
• Korea, Republic of
  • Goyang-si, Korea, Republic of, 10408
    • Research Site
  • Seongnam-si, Korea, Republic of, 13620
    • Research Site
  • Seoul, Korea, Republic of, 05505
    • Research Site
  • Seoul, Korea, Republic of, 135-710
    • Research Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Aged at least 18 years. Patient from Asia Pacific will be enrolled only.
• Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy.
• Radiological documentation of disease progression on the last treatment administered prior to enrolling in the study: 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 may have also received additional lines of treatment.
• Documented EGFR mutation (at any time since the initial diagnosis of NSCLC) 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 and must have a negative pregnancy test.

Exclusion Criteria:

• Treatment with an EGFR-TKI (eg, erlotinib, gefitinib, icotinib or afatinib) within 8 days or approximately 5x half-life of study entry; any cytotoxic chemotherapy, investigational agents or other anticancer drugs within 14 days of study entry; previous treatment with AZD9291 or a 3rd generation EGFR TKIs; Major surgery within 4 weeks of study entry; radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of study entry; currently receiving treatment with potent inhibitors or inducers of CYP3A4.
• Any unresolved toxicities from prior therapy.
• Unstable spinal cord compression or brain metastases.
• Severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses or infection.
• Refractory nausea and vomiting, chronic gastrointestinal diseases or bowel resection.
• Cardiac disease.
• Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
• Inadequate bone marrow reserve or organ function.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD9291; Once daily tablet 80 mg	Drug: AZD9291; Once daily tablet 80 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) According to RECIST 1.1	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.	RECIST tumour assessments every 6 weeks from time of first dose until objective disease progression, for an average of approximately 12 months. Results are based on the data cut off of 04 March 2016 (about 18 weeks after LSFD).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR) According to RECIST 1.1	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.	RECIST tumour assessments every 6 weeks from time first dose until date of progression, for an average of approximately 12 months. Results are based on the data cut off of 04 March 2016 (about 18 weeks after LSFD).

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• Redacted CSP

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2015
• Primary Completion (Actual): March 4, 2016
• Study Completion (Anticipated): December 30, 2022

Study Registration Dates

• First Submitted: May 11, 2015
• First Submitted That Met QC Criteria: May 11, 2015
• First Posted (Estimate): May 13, 2015

Study Record Updates

• Last Update Posted (Actual): October 21, 2022
• Last Update Submitted That Met QC Criteria: October 20, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Phase II, Open Label, Single-arm study, Safety and Efficacy of AZD9291, Asia Pacific, NSCLC with T790M mutation within the Epidermal Growth Factor Receptor Gene
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Osimertinib
• Other Study ID Numbers: D5160C00017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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
• IPD Sharing 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
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)