A Global Study to Assess the Effects of Osimertinib in Participants With EGFRm Stage IA2-IA3 NSCLC Following Complete Tumour Resection

Non-Small Cell Lung Cancer Clinical Trial

— ADAURA2  

Official title:

A Phase III, Double-blind, Randomised, Placebo-Controlled, International Study to Assess the Efficacy and Safety of Adjuvant Osimertinib Versus Placebo in Participants With EGFR Mutation-positive Stage IA2-IA3 Non-small Cell Lung Cancer, Following Complete Tumour Resection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05120349
• Other study ID #: D516FC00001
• Secondary ID: 2021-004135-89
• Status: Recruiting
• Phase: Phase 3
• Start date: February 21, 2022
• Est. completion date: November 1, 2032

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a global study to assess the effects of osimertinib in participants with EGFRm stage IA2-IA3 non-small cell lung cancer following complete tumour resection.

Description:

This is a Phase III, double-blind, randomised, placebo-controlled, 2-arm, international study assessing the efficacy and safety of adjuvant osimertinib versus placebo in participants with stage IA2-IA3 EGFRm Non-Small Cell Lung Cancer, who have previously undergone complete tumour resection. All participants must have had a tumour which harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R). Eligible participants will be randomised in a 1:1 ratio to one of the 2 intervention arms: osimertinib 80 mg or matching placebo, once daily for 3 years unless discontinuation criteria is met.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 380
• Est. completion date: November 1, 2032
• Est. primary completion date: August 2, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

1. Male or female, at least = 18 years.

2. NSCLC, of non-squamous histology.

3. Stage IA2 or IA3 disease, based on TNM8 classification.

4. Complete surgical resection (R0) of the primary NSCLC by lobectomy, segmentectomy or sleeve resection.

5. Complete recovery from surgery at the time of randomisation. Study intervention cannot commence within 4 weeks following surgery. No more than 12 weeks may have elapsed between surgery and randomisation for participants.

6. World Health Organization performance status of 0 or 1.

7. Provision of tumour sample for central pathology assessment of pathologic risk factors and to assess EGFR mutation status prior to randomisation.

8. A tumour which harbours one of the 2 EGFR mutations (Ex19del, L858R) by cobas® EGFR Mutation Test v2 (Roche Diagnostics) or FoundationOne® test.

9. Minimum life expectancy of > 6 months.

10. Females must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of child-bearing potential, or must have evidence of non-child-bearing potential. Male subjects must be willing to use barrier contraception. Exclusion Criteria

1. Mixed small cell and non-small cell cancer history.

2. Participants with incomplete (R1/R2) resection, or who have undergone pneumonectomy, bilobectomy or only wedge resection.

3. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C and HIV.

4. History of another primary malignancy except for malignancy treated with curative intent with no known active disease = 5 years before the first dose of study intervention and of low potential risk for recurrence.

5. Any of the following cardiac criteria:

• Mean resting QTc interval > 470 ms, obtained from triplicate ECGs performed at screening.
• Any abnormalities in rhythm, conduction, or morphology of resting ECG,
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events.

6. History of interstitial lung disease.

7. Inadequate bone marrow reserve or organ function.

8. Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study intervention.

9. Prior treatment with any anticancer therapy for NSCLC (including chemotherapy, radiotherapy, immunotherapy, and EGFR-TKIs).

10. Major surgery or significant traumatic injury within 4 weeks of the first dose of study intervention.

11. Participants currently receiving medications or herbal supplements known to be strong inducers of CYP3A4.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Osimertinib
The initial dose of Osimertinib 80mg once daily can be reduced to 40mg once daily. Treatment can continue until disease recurrence, unacceptable toxicity or other discontinuation criteria are met.
• Placebo
Matching placebo. Initial dose of 80mg once daily can be reduced to 40mg once daily.

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Cipolletti
Argentina	Research Site	La Plata
Argentina	Research Site	Rosario
Argentina	Research Site	Rosario
Argentina	Research Site	S.C. De Bariloche
Brazil	Research Site	Barretos
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Blumenau
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Recife
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Toronto
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	Changchun
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Fuzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guiyang
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Harbin
China	Research Site	Jinan
China	Research Site	Luoyang
China	Research Site	Nanjing
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	Suzhou
China	Research Site	Taiyuan
China	Research Site	Wuhan
China	Research Site	Xi'an
China	Research Site	Xintai
China	Research Site	Yangzhou
China	Research Site	Zhengzhou
Germany	Research Site	Berlin
Germany	Research Site	Esslingen
Germany	Research Site	Georgsmarienhuette
Germany	Research Site	Hannover
Germany	Research Site	Homburg
Germany	Research Site	Lübeck
Germany	Research Site	München
Germany	Research Site	Oldenburg
Germany	Research Site	Würzburg
Italy	Research Site	Bari
Italy	Research Site	Catania
Italy	Research Site	Firenze
Italy	Research Site	Genova
Italy	Research Site	Milan
Italy	Research Site	Napoli
Italy	Research Site	Padova
Italy	Research Site	Parma
Italy	Research Site	Roma
Italy	Research Site	Torino
Japan	Research Site	Chiba-shi
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Kashiwa
Japan	Research Site	Koto-ku
Japan	Research Site	Kyoto-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Niigata-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osakasayama-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Sunto-gun
Japan	Research Site	Wakayama-shi
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Cheongju-si
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Jinju-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon
Korea, Republic of	Research Site	Suwon
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Kuching
Malaysia	Research Site	Pulau Pinang
Malaysia	Research Site	Selangor
Poland	Research Site	Bystra
Poland	Research Site	Kraków
Poland	Research Site	Lublin
Poland	Research Site	Olsztyn
Poland	Research Site	Poznan
Poland	Research Site	Szczecin
Poland	Research Site	Warszawa
Romania	Research Site	Bucharest
Romania	Research Site	Bucuresti
Romania	Research Site	Craiova
Romania	Research Site	Floresti
Romania	Research Site	Galati
Romania	Research Site	Ovidiu
Russian Federation	Research Site	Kazan
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Nizhny Novgorod
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Perm
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Singapore	Research Site	Singapore
Singapore	Research Site	Singapore
Spain	Research Site	Barcelona
Spain	Research Site	Málaga
Spain	Research Site	Valencia
Spain	Research Site	Vigo
Spain	Research Site	Zaragoza
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taoyuan
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Hat Yai
Thailand	Research Site	Khon Kaen
Thailand	Research Site	Muang
Turkey	Research Site	Ankara
Turkey	Research Site	Bursa
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Turkey	Research Site	Kadikoy/Istanbul
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Blackpool
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Nottingham
United Kingdom	Research Site	Wythenshawe
United States	Research Site	Anchorage	Alaska
United States	Research Site	Atlanta	Georgia
United States	Research Site	Brooklyn	New York
United States	Research Site	Chicago	Illinois
United States	Research Site	Flushing	New York
United States	Research Site	Fort Belvoir	Virginia
United States	Research Site	Frederick	Maryland
United States	Research Site	Grand Junction	Colorado
United States	Research Site	Greensboro	North Carolina
United States	Research Site	Houston	Texas
United States	Research Site	Lexington	Kentucky
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Morristown	New Jersey
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Newark	Delaware
United States	Research Site	Orange	California
United States	Research Site	San Francisco	California
United States	Research Site	Seattle	Washington
United States	Research Site	Syracuse	New York
United States	Research Site	White Plains	New York
United States	Research Site	Winston-Salem	North Carolina
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh city

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Brazil,  Canada,  China,  Germany,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Poland,  Romania,  Russian Federation,  Singapore,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-Free Survival (DFS) in high-risk stratum	DFS is defined as the time from the date of randomisation until the date of disease recurrence or date of death (by any cause in the absence of recurrence), whichever occurs first.; Stratification to the high risk stratum will be based on pathologic features assessed by central pathology review during screening.	From date of randomisation up to approximately 10 years
Secondary	Disease-Free Survival (DFS) in overall population	DFS is defined as the time from the date of randomisation until the date of disease recurrence or date of death (by any cause in the absence of recurrence), whichever occurs first.	From date of randomisation up to approximately 10 years
Secondary	Overall Survival (OS) in high-risk stratum and the overall population	OS is defined as the time from the date of randomisation until death due to any cause.	From date of randomization up to approximately 10 years
Secondary	PK plasma concentrations of osimertinib and of metabolite AZ5104 in overall population	Ratio of metabolite-to-osimertinib to be calculated at predose, and at 0.5-2 hours postdose.	From date of randomisation up to approximately 10 years
Secondary	Impact of osimertinib versus placebo on physical functioning	Assess the impact of osimertinib versus placebo on physical functioning in both the high-risk stratum and the overall population as measured by SF-36 V2 health survey	From date of randomisation up to approximately 10 years
Secondary	Central Nervous System (CNS) Disease-Free Survival (DFS) in both the high-risk stratum and the overall population	CNS DFS is defined as the time from randomisation to the time of a CNS lesion (as assessed by investigator) or death due to any cause, regardless of whether the participant withdraws from study intervention or receives other anti-cancer therapy.	From date of randomisation up to approximately 10 years
Secondary	Safety and tolerability in overall population	AEs graded by CTCAE version 5.0	From date of randomisation up to approximately 10 years