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ADAURA2: A Global Study to Assess the Effects of Osimertinib in Participants With EGFRm Stage IA2-IA3 NSCLC Following Complete Tumour Resection

Sponsor
AstraZeneca (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05120349
Collaborator
(none)
380
Enrollment
159
Locations
2
Arms
128.3
Anticipated Duration (Months)
2.4
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
380 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Feb 21, 2022
Anticipated Primary Completion Date :
Aug 2, 2027
Anticipated Study Completion Date :
Nov 1, 2032

Arms and Interventions

Arm Intervention/Treatment
Experimental: Osimertinib

Osimertinib 80mg, orally, once daily (Dose may be reduced to 40 mg once daily if required at the discretion of the investigator)

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.
Other Names:
  • AZD9291; TAGRISSO

    		•
    Placebo Comparator: Placebo

    Matching placebo for osimertinib, orally, once daily

    Drug: Placebo
    Matching placebo. Initial dose of 80mg once daily can be reduced to 40mg once daily.

    Outcome Measures

    Primary Outcome Measures

    1. Disease-Free Survival (DFS) in high-risk stratum [From date of randomisation up to approximately 10 years]

      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.

    Secondary Outcome Measures

    1. Disease-Free Survival (DFS) in overall population [From date of randomisation up to approximately 10 years]

      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.

    2. Overall Survival (OS) in high-risk stratum and the overall population [From date of randomization up to approximately 10 years]

      OS is defined as the time from the date of randomisation until death due to any cause.

    3. PK plasma concentrations of osimertinib and of metabolite AZ5104 in overall population [From date of randomisation up to approximately 10 years]

      Ratio of metabolite-to-osimertinib to be calculated at predose, and at 0.5-2 hours postdose.

    4. Impact of osimertinib versus placebo on physical functioning [From date of randomisation up to approximately 10 years]

      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

    5. Central Nervous System (CNS) Disease-Free Survival (DFS) in both the high-risk stratum and the overall population [From date of randomisation up to approximately 10 years]

      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.

    6. Safety and tolerability in overall population [From date of randomisation up to approximately 10 years]

      AEs graded by CTCAE version 5.0

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    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.

    1. History of interstitial lung disease.

    2. Inadequate bone marrow reserve or organ function.

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

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

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

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Anchorage Alaska United States 99508
    2 Research Site Los Angeles California United States 90024
    3 Research Site Orange California United States 92868
    4 Research Site San Francisco California United States 94143
    5 Research Site Atlanta Georgia United States 30322
    6 Research Site Chicago Illinois United States 60612
    7 Research Site Lexington Kentucky United States 40508
    8 Research Site Louisville Kentucky United States 40217
    9 Research Site Frederick Maryland United States 21702
    10 Research Site Morristown New Jersey United States 07960
    11 Research Site New York New York United States 10029
    12 Research Site Greensboro North Carolina United States 27403
    13 Research Site Winston-Salem North Carolina United States 27157
    14 Research Site Fort Belvoir Virginia United States 22060
    15 Research Site Seattle Washington United States 98101
    16 Research Site Walla Walla Washington United States 99362
    17 Research Site Caba Argentina 1426
    18 Research Site Caba Argentina C1012AAR
    19 Research Site Rosario Argentina S2000DEJ
    20 Research Site Barretos Brazil 14784-400
    21 Research Site Blumenau Brazil 89030-101
    22 Research Site Ibirapuera Brazil 04501-000
    23 Research Site Porto Alegre Brazil 90610-000
    24 Research Site Recife Brazil 52010-075
    25 Research Site Rio de Janeiro Brazil 22271-110
    26 Research Site Sao Paulo Brazil 01327-001
    27 Research Site Montreal Quebec Canada H2X 3J4
    28 Research Site Montreal Quebec Canada H4A 3J1
    29 Research Site Toronto Canada M5G 2M9
    30 Research Site Beijing China 100029
    31 Research Site Beijing China 100142
    32 Research Site Beijing China 100191
    33 Research Site Beijing China 100210
    34 Research Site Beijing China 100730
    35 Research Site Beijing China 102218
    36 Research Site Changchun China 130012
    37 Research Site Changchun China
    38 Research Site Changsha China 410013
    39 Research Site Changsha China 430033
    40 Research Site Chengdu China 610000
    41 Research Site Fuzhou China 350014
    42 Research Site Guangzhou China 510060
    43 Research Site Guangzhou China 510100
    44 Research Site Guiyang China 550002
    45 Research Site Hangzhou China 310003
    46 Research Site Hangzhou China 310022
    47 Research Site Harbin China 150049
    48 Research Site Jinan China 2501117
    49 Research Site Nanjing China 210029
    50 Research Site Shanghai China 200030
    51 Research Site Shanghai China 200032
    52 Research Site Shanghai China 200433
    53 Research Site Shenyang China 110001
    54 Research Site Shenzhen China 518116
    55 Research Site Suzhou China 215006
    56 Research Site Taiyuan China 030000
    57 Research Site Wuhan China 430060
    58 Research Site Xi'an China 710061
    59 Research Site Xintai China 54031
    60 Research Site Xuhui District China 200032
    61 Research Site Yangzhou China 225001
    62 Research Site Zhengzhou China 450008
    63 Research Site Berlin Germany 13125
    64 Research Site Esslingen Germany 73730
    65 Research Site Georgsmarienhuette Germany 49124
    66 Research Site Hannover Germany 30625
    67 Research Site Homburg Germany 66421
    68 Research Site Lübeck Germany 23538
    69 Research Site München Germany 81377
    70 Research Site Oldenburg Germany 26121
    71 Research Site Würzburg Germany 97067
    72 Research Site Bari Italy 70124
    73 Research Site Catania Italy 95100
    74 Research Site Firenze Italy 50134
    75 Research Site Genova Italy 16132
    76 Research Site Milan Italy 20141
    77 Research Site Napoli Italy 80131
    78 Research Site Padova Italy 35128
    79 Research Site Parma Italy 43100
    80 Research Site Roma Italy 00144
    81 Research Site Torino Italy 10122
    82 Research Site Chiba-shi Japan 260-0877
    83 Research Site Fukuoka-shi Japan 812-8582
    84 Research Site Hiroshima-shi Japan 734-8551
    85 Research Site Kashiwa Japan 227-8577
    86 Research Site Koto-ku Japan 135-8550
    87 Research Site Kyoto-shi Japan 606-8507
    88 Research Site Nagoya-shi Japan 464-8681
    89 Research Site Niigata-shi Japan 951-8566
    90 Research Site Osaka-shi Japan 541-8567
    91 Research Site Osakasayama-shi Japan 589-8511
    92 Research Site Sendai-shi Japan 980-0873
    93 Research Site Shinjuku-ku Japan 160-0023
    94 Research Site Sunto-gun Japan 411-8777
    95 Research Site Busan Korea, Republic of 48108
    96 Research Site Cheongju-si Korea, Republic of 28644
    97 Research Site Daegu Korea, Republic of 42415
    98 Research Site Gyeongsangnam-do Korea, Republic of 52727
    99 Research Site Seoul Korea, Republic of 03080
    100 Research Site Seoul Korea, Republic of 07061
    101 Research Site Seoul Korea, Republic of 138-736
    102 Research Site Suwon Korea, Republic of 16247
    103 Research Site Suwon Korea, Republic of 16499
    104 Research Site Kuala Lumpur Malaysia 59100
    105 Research Site Kuching Malaysia 93586
    106 Research Site Pulau Pinang Malaysia 10450
    107 Research Site Selangor Malaysia 46050
    108 Research Site Olsztyn Poland 10-357
    109 Research Site Poznań Poland 60-569
    110 Research Site Warszawa Poland 01-138
    111 Research Site Bucharest Romania 050098
    112 Research Site Galati Romania 6200
    113 Research Site Kazan Russian Federation 420029
    114 Research Site Moscow Russian Federation 125284
    115 Research Site Moscow Russian Federation 143423
    116 Research Site Nizhny Novgorod Russian Federation 603126
    117 Research Site Novosibirsk Russian Federation 630099
    118 Research Site Perm Russian Federation 614990
    119 Research Site Saint Petersburg Russian Federation 191036
    120 Research Site Saint Petersburg Russian Federation 197022
    121 Research Site Saint Petersburg Russian Federation 197758
    122 Research Site Singapore Singapore 169610
    123 Research Site Singapore Singapore 308433
    124 Research Site Barcelona Spain
    125 Research Site Málaga Spain 29010
    126 Research Site Valencia Spain 46010
    127 Research Site Vigo Spain 36312
    128 Research Site Zaragoza Spain 50009
    129 Research Site Taichung Taiwan 40201
    130 Research Site Taichung Taiwan 40705
    131 Research Site Tainan Taiwan 70403
    132 Research Site Taipei City Taiwan 114
    133 Research Site Taipei Taiwan 100
    134 Research Site Taipei Taiwan 11217
    135 Research Site Taipei Taiwan 235
    136 Research Site Taoyuan Taiwan 333
    137 Research Site Bangkok Thailand 10300
    138 Research Site Bangkok Thailand 10330
    139 Research Site Bangkok Thailand 10700
    140 Research Site Hat Yai Thailand 90110
    141 Research Site Khon Kaen Thailand 40002
    142 Research Site Muang Thailand 50200
    143 Research Site Ankara Turkey 06010
    144 Research Site Bursa Turkey 16059
    145 Research Site Istanbul Turkey
    146 Research Site Izmir Turkey 35040
    147 Research Site Kadıkoy/Istanbul Turkey 34722
    148 Research Site Birmingham United Kingdom B9 5SS
    149 Research Site Blackpool United Kingdom FY3 8NR
    150 Research Site Headington United Kingdom OX3 7LE
    151 Research Site London United Kingdom SE1 9RT
    152 Research Site London United Kingdom SW10 9NH
    153 Research Site London United Kingdom SW3 6NP
    154 Research Site Nottingham United Kingdom NG5 1PB
    155 Research Site Wythenshawe United Kingdom M23 9LT
    156 Research Site Hanoi Vietnam 100000
    157 Research Site Hanoi Vietnam 100000
    158 Research Site Ho Chi Minh city Vietnam 700000
    159 Research Site Ho Chi Minh Vietnam 700000

    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    • Principal Investigator: Jonathan Goldman, MD, UCLA Department of Medicine
    • Principal Investigator: Yasuhiro Tsutani, MD, PhD, Kindai University Facility of Medicine
    • Principal Investigator: Jie He, MD, PhD, The Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS)

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT05120349
    Other Study ID Numbers:
    • D516FC00001
    First Posted:
    Nov 15, 2021
    Last Update Posted:
    Jul 21, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by AstraZeneca
    Osimertinib
    Tagrisso
    NSCLC
    Non-small Cell Lung Cancer
    Resectable
    EGFRm Positive
    Adjuvant
    Stage IA2-IA3
    Additional relevant MeSH terms:
    Lung Neoplasms
    Carcinoma, Non-Small-Cell Lung
    Osimertinib

    Study Results

    No Results Posted as of Jul 21, 2022