Clinical trial NCT05120349: A Global Study to Assess the Effects of Osimertinib in Participants With EGFRm Stage IA2-IA3 NSCLC Following Complete Tumour Resection
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer
Keywords: Osimertinib
Tagrisso
NSCLC
Non-small Cell Lung Cancer
Resectable
EGFRm Positive
Adjuvant
Stage IA2-IA3
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2021-11-15
Enrollment: 390
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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, bilobectomy, 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 or only wedge resection.
3. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including HCV and HIV or active uncontrolled HBV infection.
4. History of another primary malignancy, including any known or suspected synchronous primary lung cancer 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 QTcF 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 QTcF 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.

Primary outcomes:
measure: Disease-Free Survival (DFS) in high-risk stratum
timeFrame: From date of randomisation up to approximately 10 years
Secondary outcomes:
measure: Disease-Free Survival (DFS) in overall population
timeFrame: From date of randomisation up to approximately 10 years
measure: Overall Survival (OS) in high-risk stratum and the overall population
timeFrame: From date of randomization up to approximately 10 years
measure: PK plasma concentrations of osimertinib and of metabolite AZ5104 in overall population
timeFrame: From date of randomisation up to approximately 10 years
measure: Impact of osimertinib versus placebo on physical functioning
timeFrame: From date of randomisation up to approximately 10 years
measure: Central Nervous System (CNS) Disease-Free Survival (DFS) in both the high-risk stratum and the overall population
timeFrame: From date of randomisation up to approximately 10 years
measure: Safety and tolerability in overall population
timeFrame: From date of randomisation up to approximately 10 years
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Research Site
state: Alaska
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: Grand Junction
country: United States
facility: Research Site
state: Colorado
city: Newark
country: United States
facility: Research Site
state: Delaware
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Frederick
country: United States
facility: Research Site
state: Maryland
city: Morristown
country: United States
facility: Research Site
state: New Jersey
city: Flushing
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: White Plains
country: United States
facility: Research Site
state: New York
city: Houston
country: United States
facility: Research Site
state: Texas
city: Fort Belvoir
country: United States
facility: Research Site
state: Virginia
city: Buenos Aires
country: Argentina
facility: Research Site
city: Caba
country: Argentina
facility: Research Site
city: Cipolletti
country: Argentina
facility: Research Site
city: La Plata
country: Argentina
facility: Research Site
city: Rosario
country: Argentina
facility: Research Site
city: Rosario
country: Argentina
facility: Research Site
city: S.C. De Bariloche
country: Argentina
facility: Research Site
city: Barretos
country: Brazil
facility: Research Site
city: Belo Horizonte
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Recife
country: Brazil
facility: Research Site
city: Rio de Janeiro
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Toronto
country: Canada
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Fuzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Harbin
country: China
facility: Research Site
city: Jinan
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenzhen
country: China
facility: Research Site
city: Suzhou
country: China
facility: Research Site
city: Taiyuan
country: China
facility: Research Site
city: Xi'an
country: China
facility: Research Site
city: Xintai
country: China
facility: Research Site
city: Yangzhou
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Esslingen
country: Germany
facility: Research Site
city: Georgsmarienhuette
country: Germany
facility: Research Site
city: Lübeck
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Würzburg
country: Germany
facility: Research Site
city: Bari
country: Italy
facility: Research Site
city: Catania
country: Italy
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Milan
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Parma
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Chiba-shi
country: Japan
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Hiroshima-shi
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
facility: Research Site
city: Kyoto-shi
country: Japan
facility: Research Site
city: Niigata-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Osakasayama-shi
country: Japan
facility: Research Site
city: Sendai-shi
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Sunto-gun
country: Japan
facility: Research Site
city: Wakayama-shi
country: Japan
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Jinju-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon
country: Korea, Republic of
facility: Research Site
city: Suwon
country: Korea, Republic of
facility: Research Site
city: Kuala Lumpur
country: Malaysia
facility: Research Site
city: Kuching
country: Malaysia
facility: Research Site
city: Pulau Pinang
country: Malaysia
facility: Research Site
city: Selangor
country: Malaysia
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Bucharest
country: Romania
facility: Research Site
city: Bucuresti
country: Romania
facility: Research Site
city: Perm
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Vigo
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Hat Yai
country: Thailand
facility: Research Site
city: Khon Kaen
country: Thailand
facility: Research Site
city: Muang
country: Thailand
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Bursa
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Kadıkoy/Istanbul
country: Turkey
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: Blackpool
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
city: Wythenshawe
country: United Kingdom
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh city
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
Study officials:
affiliation: University of California, Los Angeles
name: Jonathan Goldman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kindai University Facility of Medicine
name: Yasuhiro Tsutani, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS)
name: Jie He, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: