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

NCT02094261 | Completed Phase 2 Results

• 2 other identifiers: D5160C000022014-000531-17
• Study Type: interventional
• Target: 210
• Locations: 8 countries
• Sites: 44

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

Conditions

Non Small Cell Lung Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Duration of Response (DoR)

  RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis)

• Disease Control Rate (DCR)

  RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis)

• Progression-Free Survival (PFS)

  RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis)

Study Arms (1)

AZD9291

EXPERIMENTAL

Once daily tablet 80 mg

Drug: AZD9291

Interventions

AZD9291 DRUG

Once daily tablet 80 mg

AZD9291

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (44)

Research Site

La Jolla, California, 92093, United States

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Orange, California, 92868, United States

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New Haven, Connecticut, 06510, United States

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Norwalk, Connecticut, 06850, United States

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Indianapolis, Indiana, 46202, United States

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Boston, Massachusetts, 02215, United States

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Lebanon, New Hampshire, 03756, United States

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New York, New York, 10032, United States

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Durham, North Carolina, 27710, United States

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Edmonton, Alberta, T6G 1Z2, Canada

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Ottawa, Ontario, K1H 8L6, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Hong Kong, Hong Kong

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Shatin, 00000, Hong Kong

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Milan, 20141, Italy

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Milan, 20132, Italy

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Napoli, 80131, Italy

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Perugia, 06132, Italy

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Verona, 37134, Italy

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Akashi-shi, 673-8558, Japan

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Chūōku, 104-0045, Japan

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Kitaadachi-gun, 362-0806, Japan

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Kitakyushu-shi, 802-0077, Japan

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Kōtoku, 135-8550, Japan

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Nagoya, 460-0001, Japan

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Nagoya, 464-8681, Japan

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Niigata, 951-8566, Japan

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Osaka, 534-0021, Japan

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Osaka, 541-8567, Japan

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Sakaishi, 591-8555, Japan

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Sayama, 589-8511, Japan

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Wakayama, 641-8510, Japan

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Yokohama, 236-0051, Japan

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Goyang-si, 10408, South Korea

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Seongnam-si, 13620, South Korea

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Seoul, 06591, South Korea

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A Coruña, 15006, Spain

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Barcelona, 08025, Spain

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Madrid, 28007, Spain

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Majadahonda, 28222, Spain

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Málaga, 29010, Spain

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Valencia, 46026, Spain

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Taichung, 40705, Taiwan

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Taipei, 112, Taiwan

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Related Publications (5)

• Murat-Onana ML, Ramalingam SS, Janne PA, Gray JE, Ahn MJ, John T, Yatabe Y, Huang X, Rukazenkov Y, Javey M, Brown H, Li-Sucholeiki X. EGFR mutation testing across the osimertinib clinical program. Lung Cancer. 2025 Jun;204:108549. doi: 10.1016/j.lungcan.2025.108549. Epub 2025 Apr 18.

  PMID: 40311309 DERIVED

• 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.

  PMID: 31345012 DERIVED

• 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.

  PMID: 30512189 DERIVED

• 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.

  PMID: 29293889 DERIVED

• 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.

  PMID: 27751847 DERIVED

Related Links

• D5160C00002\_12\_1\_01csp\_andamendments\_Redacted1
• CSR synopsis

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Senior Medical Director, Tagrisso
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• Glenwood Goss, MD

  501 Smyth Road, Ottawa, Canada

  PRINCIPAL INVESTIGATOR

• Tetsuya Mitsudomi, MD

  Kinki University Hospital, Faculty of Medicine, Osaka, Japan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2014
• First Posted: March 21, 2014
• Study Start: May 20, 2014
• Primary Completion: May 1, 2015
• Study Completion: November 7, 2023
• Last Updated: November 6, 2024
• Results First Posted: June 7, 2016

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, 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

Locations

JP (14); HK (2); KR (3); CA (3); IT (5); TW (2); ES (6); US (9)