Real World Treatment Study of AZD9291 for Advanced/Metastatic EGFR T790M Mutation NSCLC

Lung Cancer Clinical Trial

— ASTRIS  

Official title:

Open Label, Multinational, Multicenter, Real World Treatment Study of Single Agent AZD9291 for Patients With Advanced/Metastatic Epidermal Growth Factor Receptor (EGFR) T790M Mutation-Positive Non-Small Cell Lung Cancer (NSCLC) Who Have Received Prior Therapy With an EGFR Tyrosine Kinase Inhibitor (EGFR-TKI)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02474355
• Other study ID #: D5160C00022
• Status: Completed
• Phase: Phase 3
• Start date: September 18, 2015
• Est. completion date: April 18, 2019

Study information

• Verified date: November 2021
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to assess the efficacy and safety of single agent AZD9291 in a real world setting in adult patients with advanced or metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive Non-Small Cell Lung Cancer (NSCLC), who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy.

Description:

Objective: The primary objective of this study is to assess the efficacy and safety of single agent AZD9291 in a real world setting in adult patients with advanced or metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive Non-Small Cell Lung Cancer (NSCLC), who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy.

Study site(s) and number of patients planned: Approximately 1500 patients will be recruited in Europe. The recruitment will be increased beyond that as the study will expand in other regions of the world (America, Asia).

Study Design This will be an open-label, single-arm, multinational, multicenter, real world treatment study.

Target patient population: Adult patients (fulfilling the definition of "age of majority" per local regulations) with locally advanced (stage IIIB) or metastatic (stage IV) NSCLC with confirmed T790M mutation, who have received prior EGFR-TKI therapy.

Investigational product (IP), dosage, and mode of administration: AZD9291 is an oral, potent, selective, irreversible inhibitor of both EGFR-TKI sensitising and resistance mutations in NSCLC with a significant selectivity margin over wild-type EGFR. AZD9291 will be administered orally as one 80 mg tablet once a day.

Duration of IP administration: Patients may continue to receive AZD9291 as long as they continue to show clinical benefit, as judged by the investigator, and in the absence of discontinuation criteria). The study will be closed in each participating country as soon as possible following national reimbursement of AZD9291 in that country (up to a max of 90 days post reimbursement). Enrolment will be closed within 6 months after market license approval in that country or at national reimbursement, whichever is sooner. Patients withdrawing from the treatment prior to national reimbursement will be followed up as part of this study. Patients on treatment will receive commercial supply until documented disease progression as per investigator assessment.

In the event that national reimbursement should not be granted following a reasonable time after market license approval in the country, the study will be closed in a maximum period of 18 months after the last patient is enrolled in that country. If applicable, timelines for conversion to commercial drug will be agreed with local bodies which may include regulatory agencies, ethics committees, and institutions. Patient will be followed until death or lost to follow-up.

Study measures: Data collected will include patient demographics, information needed to determine patient eligibility (including medical history, past and current disease characteristics, and tumor EGFR mutational status), AZD9291 exposure, investigator-reported efficacy (including tumor response and disease progression), overall survival (OS), and safety (including serious adverse events [SAEs], adverse events leading to dose modification, and adverse events of special interest [interstitial lung disease/pneumonitis-like events, and QTc prolongation events]).

Statistical methods: All data will be presented for the overall full analysis/evaluable set, and also by cohorts defined by number and type of previous treatment lines for the advanced disease. Descriptive statistics will be used for all variables, as appropriate. Continuous variables will be summarised by the number of observations, mean, standard deviation, median, minimum, and maximum. Categorical variables will be summarised by frequency counts and percentages for each category. OS and PFS will be summarized using Kaplan-Meier estimates of the median time to death or censoring and quartiles together with their 95% confidence intervals.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3017
• Est. completion date: April 18, 2019
• Est. primary completion date: April 18, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

1. Provision of signed and dated written informed consent by the patient or legally acceptable representative prior to any study-specific procedures

2. Adults (according to each country regulations for age of majority)

3. Locally advanced (stage IIIB) or metastatic (stage IV) EGFRm NSCLC, not amenable to curative surgery or radiotherapy, with confirmation of the presence of the T790M mutation

4. Prior therapy with an EGFR-TKI. Patients may have also received additional lines of treatment

5. World Health Organization (WHO) performance status 0-2

6. Adequate bone marrow reserve and organ function as demonstrated by complete blood count, biochemistry in blood and urine at baseline (please refer to IB for guidance)

7. ECG recording at baseline showing absence of any cardiac abnormality as per exclusion criterion #6

8. Female patients of childbearing potential must be using adequate contraceptive measures, must not be breast feeding, and must have a negative pregnancy test prior to start of dosing. Otherwise, they must have evidence of nonchildbearing potential

9. Male patients must be willing to use barrier contraception, i.e., condoms

Exclusion Criteria:

1. Previous (within 6 months) or current treatment with AZD9291

2. Patients currently receiving (or unable to stop use at least 1 week prior to receiving the first dose of AZD9291) any treatment known to be potent inhibitors or inducers of cytochrome P450 (CYP) 3A4

3. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, active infection including hepatitis B, hepatitis C, and human immunodeficiency virus, or significantly impaired bone marrow reserve or organ function, including hepatic and renal impairment, which in the investigator's opinion would significantly alter the risk/benefit balance.

4. Patient with symptomatic central nervous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids to manage CNS symptoms within the 2 weeks prior to start AZD9291 administration;

5. Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD

6. Any of the following cardiac criteria:

1. Mean resting corrected QT interval (QTcF) > 470 ms using Fredericia's formula :

2. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block)

3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events

7. Any unresolved toxicity from prior therapy CTCAE > grade 3 at the time of starting treatment

8. History of hypersensitivity to excipients of AZD9291 or to drugs with a similar chemical structure or class to AZD9291

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms

Intervention

Procedure:
• T790M+ Testing
If a previous lab report is unavailable, the patient will need to have T790M+ testing.
• Baseline Visit Blood & Urine Testing
Blood count and standard chemistry testing to ensure patient meets inclusion/exclusion criteria
• Baseline ECG
ECG to ensure absence of any cardiac abnormality
• Visual Slit-Lamp Testing
Slit-lamp testing performed to ensure patients do not have any eye abnormalities or symptoms

Drug:
• AZD9291 Dosing
Patients to be provided with AZD9291 every 6 weeks (+/- 7 days)

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Australia	Research Site	Bedford Park
Australia	Research Site	East Melbourne
Australia	Research Site	Kurralta Park
Australia	Research Site	Randwick
Australia	Research Site	Waratah
Austria	Research Site	Innsbruck
Austria	Research Site	Linz
Austria	Research Site	Salzburg
Austria	Research Site	Wien
Belgium	Research Site	Charleroi
Belgium	Research Site	Edegem
Belgium	Research Site	Leuven
Brazil	Research Site	Barretos
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Florianópolis
Brazil	Research Site	Ijui
Brazil	Research Site	Itajai
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Salvador
Brazil	Research Site	Salvador
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Canada	Research Site	Burnaby	British Columbia
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	North York	Ontario
Canada	Research Site	Oshawa	Ontario
Canada	Research Site	Quebec
Canada	Research Site	Regina, Saskatchewan
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Chongqing
China	Research Site	ChongQing
China	Research Site	Chongqing
China	Research Site	Dalian
China	Research Site	Fuzhou
China	Research Site	Fuzhou
China	Research Site	Fuzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	GuangZhou
China	Research Site	Haikou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Harbin
China	Research Site	Hefei
China	Research Site	Hohhot
China	Research Site	Ji Nan
China	Research Site	Kunming
China	Research Site	Linhai
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Nanjing
China	Research Site	Nanjing
China	Research Site	Nanjing
China	Research Site	Nanjing
China	Research Site	Nanning
China	Research Site	Nantong
China	Research Site	Qingdao
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Shenyang
China	Research Site	Shenzhen
China	Research Site	Shijiahzhuang
China	Research Site	Tianjin
China	Research Site	Urumqi
China	Research Site	Urumqi
China	Research Site	Urumqi
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Wuxi
China	Research Site	Xi'an
China	Research Site	Xi'an
China	Research Site	Yancheng
China	Research Site	Yangzhou
China	Research Site	Yantai
China	Research Site	Zhengzhou
Denmark	Research Site	Vejle
Ireland	Research Site	Dublin
Italy	Research Site	Ancona
Italy	Research Site	Avellino
Italy	Research Site	Bari
Italy	Research Site	Bologna
Italy	Research Site	Brescia
Italy	Research Site	Cagliari
Italy	Research Site	Catania
Italy	Research Site	Firenze
Italy	Research Site	Genova
Italy	Research Site	Lecce
Italy	Research Site	Livorno
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Novara
Italy	Research Site	Palermo
Italy	Research Site	Parma
Italy	Research Site	Perugia
Italy	Research Site	Pisa
Italy	Research Site	Reggio Emilia
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Udine
Italy	Research Site	Verona
Korea, Republic of	Research Site	Anyang
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Cheongju-si
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Daejeon
Korea, Republic of	Research Site	Gangneung-si
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Jeonju-si
Korea, Republic of	Research Site	Jeonnam
Korea, Republic of	Research Site	JinJoo
Korea, Republic of	Research Site	Seo-gu
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon-si
Korea, Republic of	Research Site	Ulsan
Saudi Arabia	Research Site	Dammam
Saudi Arabia	Research Site	Riyadh
Spain	Research Site	A Coruña
Spain	Research Site	Alicante
Spain	Research Site	Badalona
Spain	Research Site	Barcelona
Spain	Research Site	Castellón de la Plana
Spain	Research Site	Jaén
Spain	Research Site	Las Palmas de Gran Canaria
Spain	Research Site	León
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Majadahonda
Spain	Research Site	Oviedo
Spain	Research Site	Palma de Mallorca
Spain	Research Site	San Sebastian
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Spain	Research Site	Valencia
Spain	Research Site	Zaragoza
Sweden	Research Site	Orebro
Sweden	Research Site	Uppsala
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan
United Kingdom	Research Site	Antrim
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Norwich
United Kingdom	Research Site	Poole
United Kingdom	Research Site	Wolverhampton

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Parexel

Countries where clinical trial is conducted

Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  China,  Denmark,  Ireland,  Italy,  Korea, Republic of,  Saudi Arabia,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	OS was defined as the time, in months from the date of first dose of Osimertinib until death due to any cause, or at last documented contact with participant status "alive" (in this study any participants alive at study discontinuation, or lost to follow-up was considered being censored at study discontinuation date or at the last known date participant was alive). OS was summarized using a Kaplan-Meier (KM) estimate of the median time to death or censoring together with their 95% confidence intervals.	From the date of first dose of Osimertinib until the date of death (due to any cause) or last participant contact [up to 43 months]
Primary	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Safety assessment of Osimertinib was analyzed by evaluating AEs and SAEs.	From screening to progression follow-up [every 6 weeks +/- 1 week] relative to the date of enrolment until the end of study [up to 43 months]
Secondary	Progression Free Survival	PFS was defined as the time, in months from first dose of AZD9291/ost/study drug/ study treatment until the date of disease progression or death in the absence of progression. Participants who had not progressed or died at study discontinuation were censored at the time of the latest date of disease assessment. PFS was summarized using KM estimates of the median time to progression or death with their 95% confidence intervals.	From the date of first dose of Osimertinib until disease progression or death in the absence of progression [up to 43 months]
Secondary	Time to Treatment Discontinuation (TTD)	TTD or death was assessed as a supportive summary to PFS and defined as the time from the date of the first dose of osimertinib in the study until the date of osimertinib discontinuation or death, regardless of the reason for discontinuation. TTD was summarized using KM estimates of the median times to progression or death or treatment discontinuation.	From the date of first dose of Osimertinib until disease progression or death in the absence of progression [up to 43 months]
Secondary	Response Rate (RR)	RR was defined as the number (%) of participants with a best response (by Investigator assessment) of 'responding', regardless of the method of evaluation, and was based on a subset of the full analysis set consisting of subjects with at least one documented response assessment. RR was summarised together with the 95% CI.	From the date of first dose of Osimertinib until disease progression or death in the absence of progression [up to 43 months]

External Links

•   D5160C00022 Clinical Study Protocol
•   D5160C00022 Statistical Analysis Plan