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

Non Small Cell Lung Cancer Clinical Trial

— AURA2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02094261
• Other study ID #: D5160C00002
• Secondary ID: 2014-000531-17
• Status: Completed
• Phase: Phase 2
• Start date: May 20, 2014
• Est. completion date: November 7, 2023

Study information

• Verified date: December 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 210
• Est. completion date: November 7, 2023
• Est. primary completion date: May 1, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non Small Cell Lung Cancer

Intervention

Drug:
• AZD9291
Once daily tablet 80 mg

Locations

Country	Name	City	State
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Toronto	Ontario
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	Shatin
Italy	Research Site	Milan
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Perugia
Italy	Research Site	Verona
Japan	Research Site	Akashi-shi
Japan	Research Site	Chuo-ku
Japan	Research Site	Kitaadachi-gun
Japan	Research Site	Kitakyushu-shi
Japan	Research Site	Koto-ku
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Niigata-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osakasayama
Japan	Research Site	Sakai-shi
Japan	Research Site	Wakayama-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Spain	Research Site	A Coruña
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Majadahonda
Spain	Research Site	Málaga
Spain	Research Site	Valencia
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
United States	Research Site	Boston	Massachusetts
United States	Research Site	Durham	North Carolina
United States	Research Site	Indianapolis	Indiana
United States	Research Site	La Jolla	California
United States	Research Site	Lebanon	New Hampshire
United States	Research Site	New Haven	Connecticut
United States	Research Site	New York	New York
United States	Research Site	Norwalk	Connecticut
United States	Research Site	Orange	California

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Canada,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)	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 first dose until objective disease progression, up to approximately 11 months (at the time of analysis)
Secondary	Duration of Response (DoR)	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).	RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis)
Secondary	Disease Control Rate (DCR)	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 first dose until objective disease progression, up to approximately 11 months (at the time of analysis)
Secondary	Progression-Free Survival (PFS)	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.	RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis)

External Links

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