NCT02094261 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2024-11-06

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

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Objective Response Rate (ORR)

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outcome · POSTED

Duration of Response (DoR)

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outcome · POSTED

Disease Control Rate (DCR)

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outcome · POSTED

Progression-Free Survival (PFS)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility 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.
healthy Volunteers: false
maximum Age: 130 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Once daily tablet 80 mg
intervention Names
Drug: AZD9291
label
AZD9291
type
EXPERIMENTAL

interventions

arm Group Labels
AZD9291
description
Once daily tablet 80 mg
name
AZD9291
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 210
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
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)

secondary Outcomes

description
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).
measure
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)
description
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.
measure
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)
description
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.
measure
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)

Full 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
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.

Source references

references

citation
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pmid
40311309
type
DERIVED
citation
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
type
DERIVED
citation
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
type
DERIVED
citation
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
type
DERIVED
citation
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
type
DERIVED