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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT07128199




Registration number
NCT07128199
Ethics application status
Date submitted
11/08/2025
Date registered
17/08/2025
Date last updated
16/09/2025

Titles & IDs
Public title
A Study to Assess the Efficacy and Safety of Zipalertinib Versus Placebo for Adjuvant Treatment in Participants With Stage IB-IIIA NSCLC With Uncommon EGFR Mutations, Following Complete Tumor Resection
Scientific title
A Randomized, Placebo-Controlled, Double-Blind, Multi-Center Phase 3 Study of Zipalertinib Plus Adjuvant Chemotherapy Versus Placebo Plus Adjuvant Chemotherapy in Stage IB-IIIA NSCLC Patients With Uncommon EGFR Mutations Following Complete Tumor Resection (REZILIENT4)
Secondary ID [1] 0 0
2025-521775-31-00
Secondary ID [2] 0 0
TAS6417-302
Universal Trial Number (UTN)
Trial acronym
REZILIENT4
Linked study record

Health condition
Health condition(s) or problem(s) studied:
NSCLC, Stage IB-IIIA 0 0
Lung Cancer 0 0
Adjuvant 0 0
Post-surgical 0 0
EGFR 0 0
Exon 20 0 0
Early Stage Lung Cancer 0 0
Uncommon EGFR Mutations 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cisplatin
Treatment: Drugs - Carboplatin
Treatment: Drugs - Pemetrexed
Treatment: Drugs - TAS6417
Treatment: Drugs - Zipalertinib Matching-placebo

Experimental: Zipalertinib - Participants will receive adjuvant platinum-based chemotherapy consisting of cisplatin 75 milligrams per square meter (mg/m\^2) or carboplatin (area under concentration \[AUC\] 5 milligrams per milliliter per minute mg/mL/min) plus pemetrexed 500 mg/m\^2, administered via intravenous (IV) infusion, on 21-day cycle, in combination with zipalertinib 100 mg, orally, twice daily (BID).

After completion of chemotherapy, participants will continue on zipalertinib monotherapy 100 mg, orally, BID on 21-day cycle, until the participant meets any of the treatment discontinuation criteria.

Placebo comparator: Placebo - Participants will receive adjuvant platinum-based chemotherapy consisting of cisplatin 75 mg/m\^2 or carboplatin AUC 5 mg/mL/min plus pemetrexed 500 mg/m\^2, administered via IV infusion, on 21-day cycle, in combination with zipalertinib matching-placebo 100 mg, orally, BID.

After completion of chemotherapy, participants will continue on zipalertinib matching-placebo monotherapy 100mg, orally, BID on 21-day cycle, until the participant meets any of the treatment discontinuation criteria.


Treatment: Drugs: Cisplatin
IV infusion.

Treatment: Drugs: Carboplatin
IV infusion.

Treatment: Drugs: Pemetrexed
IV infusion.

Treatment: Drugs: TAS6417
Oral tablets.

Treatment: Drugs: Zipalertinib Matching-placebo
Oral tablets.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Disease-free Survival (DFS) as Assessed by the Investigator
Timepoint [1] 0 0
Up to 5 years
Secondary outcome [1] 0 0
Disease-free Survival Rate
Timepoint [1] 0 0
At 2, 3 and 5 years
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [3] 0 0
Overall Survival Rate
Timepoint [3] 0 0
At 2, 3 and 5 years
Secondary outcome [4] 0 0
DFS of Central Nervous System (cDFS)
Timepoint [4] 0 0
Up to 5 years
Secondary outcome [5] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0)
Timepoint [5] 0 0
Up to 5 years
Secondary outcome [6] 0 0
Number of Participants with Clinically Significant Changes in Clinical Laboratory Parameters
Timepoint [6] 0 0
Up to 5 years
Secondary outcome [7] 0 0
Number of Participants with Clinically Significant Changes in Vital Signs
Timepoint [7] 0 0
Up to 5 years
Secondary outcome [8] 0 0
Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Parameters
Timepoint [8] 0 0
Up to 5 years
Secondary outcome [9] 0 0
Number of Participants With Change in Left Ventricular Ejection Fraction (LVEF) Evaluated Using Electrocardiography (ECHO) and Multigated Acquisition (MUGA) Scan
Timepoint [9] 0 0
Up to 5 years
Secondary outcome [10] 0 0
Change in EuroQuality of Life-5 Dimensional 3-Level (EQ-5D-3L)
Timepoint [10] 0 0
Baseline, up to 5 years
Secondary outcome [11] 0 0
Change From Baseline in European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) Scores
Timepoint [11] 0 0
Up to 5 years

Eligibility
Key inclusion criteria
1. Histologically confirmed diagnosis of primary NSCLC on predominantly non-squamous histology.
2. Documented EGFRmt status as determined by local testing performed at a clinical laboratory improvement amendment (CLIA) certified (United States [US]) or accredited (outside of the US) local laboratory, defined as either one of the following EGFRmt:

1. exon20 insertion mutations (ex20ins) or
2. other uncommon, non-ex20ins EGFRmt (eg, G719X, L861Q, or S768I)
3. Magnetic resonance imaging (MRI) or computed tomography (CT) scan of the brain done prior to surgery. Participants in whom this was not done prior to surgery may still be enrolled if appropriate imaging (i.e., MRI or CT of the brain) is performed prior to randomization.
4. Complete surgical resection of the primary NSCLC is mandatory. All gross disease must have been removed at the end of surgery. All surgical margins of resection must be negative for tumor. Resection may be accomplished by open thoracotomy or video associated thoracic surgery (VATS) techniques.
5. Classified post-operatively as either Stage IB, IIA, IIB, or IIIA according to the tumor nodes metastasis (TNM) staging system for lung cancer (American Joint Committee on Cancer [AJCC] 9th edition).
6. Complete recovery from surgery at the time of randomization.
7. Eastern cooperative oncology group performance status (ECOG PS) of 0 or 1.
8. Archival tumor tissue available for submission, with minimum quantity sufficient to evaluate EGFRmt status and, where possible, other biomarkers.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Is currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged not to be scientifically or medically compatible with this study.
2. Treatment with any of the following within the time frame specified:

1. Zipalertinib (TAS6417/CLN-081) or any other EGFR inhibitor at any time.
2. Pre-operative or post-operative or planned radiation therapy for the current lung cancer.
3. Any prior systemic anticancer therapy (e.g., neoadjuvant chemotherapy), including investigational therapy, for treatment of NSCLC.
4. Major surgery (including primary tumor surgery, excluding placement of vascular access) within 4 weeks of the first dose of study treatment.
5. All prescribed medication, over-the-counter medication, vitamin preparations and other food supplements, or herbal medications that are strong or moderate cytochrome p450 (CYP) 3A4 inducers or inhibitors within 7 days prior to first dose.
6. Treatment with an investigational drug within five half-lives of the compound or any of its related material, if known.
3. Has received only segmentectomies or wedge resections.
4. Past medical history of interstitial lung disease (ILD)/pneumonitis, drug-induced ILD/pneumonitis or any evidence of clinically active ILD/pneumonitis.
5. Impaired cardiac function or clinically significant cardiac disease.
6. Unable to swallow tablets or has any disease or condition that may significantly affect gastrointestinal (GI) absorption of zipalertinib (such as inflammatory bowel disease, malabsorption syndrome, or prior significant bowel resection).
7. Participants with a history of any other cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, other cancers curatively treated with no evidence of disease for >5 years following the end of treatment and which, in the opinion of the treating physician, do not have a substantial risk of recurrence of the prior malignancy.
8. Known history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) that is unstable or not controlled with treatment. Screening not required.
9. Active bleeding disorders.
10. Known:

a. Hypersensitivity: i. To the ingredients in zipalertinib/placebo or any drugs similar in structure or class. ii. To platinum-containing drugs (i.e., cisplatin, carboplatin), pemetrexed, or any known excipients of these drugs. b. Contraindications to platinum-containing drugs (i.e., cisplatin, carboplatin) or pemetrexed according to the respective local labels.
11. Is unable or unwilling to take dexamethasone, folic acid, and/or vitamin B12 supplementation during treatment with pemetrexed.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/08/2025
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2032
Actual
Sample size
Target
360
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Bankstown-Lidcombe Hospital - Bankstown
Recruitment hospital [2] 0 0
GenesisCare - North Shore - St Leonards
Recruitment hospital [3] 0 0
Saint John of God - Subiaco Hospital - Subiaco
Recruitment postcode(s) [1] 0 0
2200 - Bankstown
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alaska
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Virginia
Country [11] 0 0
Argentina
State/province [11] 0 0
Buenos Aires
Country [12] 0 0
Argentina
State/province [12] 0 0
Córdoba
Country [13] 0 0
Belgium
State/province [13] 0 0
Antwerpen
Country [14] 0 0
Belgium
State/province [14] 0 0
Flemish Brabant
Country [15] 0 0
Brazil
State/province [15] 0 0
Ceará
Country [16] 0 0
Brazil
State/province [16] 0 0
Espírito Santo
Country [17] 0 0
Brazil
State/province [17] 0 0
Estado de Bahia
Country [18] 0 0
Brazil
State/province [18] 0 0
Federal District
Country [19] 0 0
Brazil
State/province [19] 0 0
Minas Gerais
Country [20] 0 0
Brazil
State/province [20] 0 0
Paraná
Country [21] 0 0
Brazil
State/province [21] 0 0
Pernambuco
Country [22] 0 0
Brazil
State/province [22] 0 0
Piauí
Country [23] 0 0
Brazil
State/province [23] 0 0
Rio de Janeiro
Country [24] 0 0
Brazil
State/province [24] 0 0
Rio Grande do Norte
Country [25] 0 0
Brazil
State/province [25] 0 0
Rio Grande do Sul
Country [26] 0 0
Brazil
State/province [26] 0 0
Santa Catarina
Country [27] 0 0
Brazil
State/province [27] 0 0
São Paulo
Country [28] 0 0
Canada
State/province [28] 0 0
Ontario
Country [29] 0 0
Canada
State/province [29] 0 0
Quebec
Country [30] 0 0
France
State/province [30] 0 0
Aquitane
Country [31] 0 0
France
State/province [31] 0 0
Aveyron
Country [32] 0 0
France
State/province [32] 0 0
Basse-Normandie
Country [33] 0 0
France
State/province [33] 0 0
Gard
Country [34] 0 0
France
State/province [34] 0 0
Grand Est
Country [35] 0 0
France
State/province [35] 0 0
Ille-et-Vilaine
Country [36] 0 0
France
State/province [36] 0 0
Loire-Atlantique
Country [37] 0 0
France
State/province [37] 0 0
Maine-et-Loire
Country [38] 0 0
France
State/province [38] 0 0
Pays de la Loire Region
Country [39] 0 0
France
State/province [39] 0 0
Rhone-Alpes
Country [40] 0 0
France
State/province [40] 0 0
Villejuif
Country [41] 0 0
France
State/province [41] 0 0
Île-de-France Region
Country [42] 0 0
Germany
State/province [42] 0 0
Baden-Wurttemberg
Country [43] 0 0
Germany
State/province [43] 0 0
Hesse
Country [44] 0 0
Germany
State/province [44] 0 0
North Rhine-Westphalia
Country [45] 0 0
Greece
State/province [45] 0 0
Attica
Country [46] 0 0
Greece
State/province [46] 0 0
Central Macedonia
Country [47] 0 0
Hong Kong
State/province [47] 0 0
Hong Kong
Country [48] 0 0
Hong Kong
State/province [48] 0 0
Kowloon
Country [49] 0 0
Italy
State/province [49] 0 0
Forlì-Cesena
Country [50] 0 0
Italy
State/province [50] 0 0
Milan
Country [51] 0 0
Italy
State/province [51] 0 0
Naples
Country [52] 0 0
Italy
State/province [52] 0 0
Ravenna
Country [53] 0 0
Italy
State/province [53] 0 0
Rome
Country [54] 0 0
Italy
State/province [54] 0 0
Torino
Country [55] 0 0
Italy
State/province [55] 0 0
Verona
Country [56] 0 0
Italy
State/province [56] 0 0
Alessandria
Country [57] 0 0
Italy
State/province [57] 0 0
Ancona
Country [58] 0 0
Italy
State/province [58] 0 0
Bergamo
Country [59] 0 0
Italy
State/province [59] 0 0
Bologna
Country [60] 0 0
Italy
State/province [60] 0 0
Catania
Country [61] 0 0
Italy
State/province [61] 0 0
Livorno
Country [62] 0 0
Italy
State/province [62] 0 0
Modena
Country [63] 0 0
Italy
State/province [63] 0 0
Pavia
Country [64] 0 0
Italy
State/province [64] 0 0
Siena
Country [65] 0 0
Japan
State/province [65] 0 0
Aiti [Aichi]
Country [66] 0 0
Japan
State/province [66] 0 0
Fukuoka
Country [67] 0 0
Japan
State/province [67] 0 0
Hirosima [Hiroshima]
Country [68] 0 0
Japan
State/province [68] 0 0
Hukuoka [Fukuoka]
Country [69] 0 0
Japan
State/province [69] 0 0
Hyogo
Country [70] 0 0
Japan
State/province [70] 0 0
Kanagawa
Country [71] 0 0
Japan
State/province [71] 0 0
Miyagi
Country [72] 0 0
Japan
State/province [72] 0 0
Nagasaki
Country [73] 0 0
Japan
State/province [73] 0 0
Osaka
Country [74] 0 0
Japan
State/province [74] 0 0
Sizuoka [Shizuoka]
Country [75] 0 0
Japan
State/province [75] 0 0
Tiba [Chiba]
Country [76] 0 0
Japan
State/province [76] 0 0
Tokyo
Country [77] 0 0
Japan
State/province [77] 0 0
Okayama
Country [78] 0 0
Malaysia
State/province [78] 0 0
Kelantan
Country [79] 0 0
Malaysia
State/province [79] 0 0
Pulau Pinang
Country [80] 0 0
Malaysia
State/province [80] 0 0
Selangor
Country [81] 0 0
Malaysia
State/province [81] 0 0
Kuala Lumpur
Country [82] 0 0
Malaysia
State/province [82] 0 0
Selangor Darul Ehsan
Country [83] 0 0
Mexico
State/province [83] 0 0
Guanajuato
Country [84] 0 0
Mexico
State/province [84] 0 0
Mexico City
Country [85] 0 0
Mexico
State/province [85] 0 0
Puebla
Country [86] 0 0
Netherlands
State/province [86] 0 0
Gelderland
Country [87] 0 0
Netherlands
State/province [87] 0 0
South Holland
Country [88] 0 0
Peru
State/province [88] 0 0
Lima region
Country [89] 0 0
Poland
State/province [89] 0 0
Greater Poland Voivodeship
Country [90] 0 0
Poland
State/province [90] 0 0
Lower Silesian Voivodeship
Country [91] 0 0
Poland
State/province [91] 0 0
Podkarpackie Voivodeship
Country [92] 0 0
Poland
State/province [92] 0 0
Warmian-Masurian Voivodeship
Country [93] 0 0
Poland
State/province [93] 0 0
Biala Podlaska
Country [94] 0 0
Romania
State/province [94] 0 0
Bucharest
Country [95] 0 0
Romania
State/province [95] 0 0
Bucure?ti
Country [96] 0 0
Romania
State/province [96] 0 0
Cluj
Country [97] 0 0
Romania
State/province [97] 0 0
Constan?a County
Country [98] 0 0
Romania
State/province [98] 0 0
Prahova
Country [99] 0 0
Romania
State/province [99] 0 0
Timi? County
Country [100] 0 0
Romania
State/province [100] 0 0
Satu Mare
Country [101] 0 0
Singapore
State/province [101] 0 0
North East
Country [102] 0 0
Singapore
State/province [102] 0 0
Singapore
Country [103] 0 0
South Korea
State/province [103] 0 0
Daegu Gwang'yeogsi [Taegu-Kwangyokshi]
Country [104] 0 0
South Korea
State/province [104] 0 0
Gyeonggi-do
Country [105] 0 0
South Korea
State/province [105] 0 0
Gyeonggido [Kyonggi-do]
Country [106] 0 0
South Korea
State/province [106] 0 0
Gyeongsangbugdo [Kyongsangbuk-do]
Country [107] 0 0
South Korea
State/province [107] 0 0
Gyeongsangnam-do
Country [108] 0 0
South Korea
State/province [108] 0 0
Gyeongsangnamdo [Kyongsangnam-do]
Country [109] 0 0
South Korea
State/province [109] 0 0
Incheon Gwang'yeogsi [Inch'on-Kwangyokshi]
Country [110] 0 0
South Korea
State/province [110] 0 0
Jeollanam-do
Country [111] 0 0
South Korea
State/province [111] 0 0
Jeonrabugdo [Chollabuk-do]
Country [112] 0 0
South Korea
State/province [112] 0 0
Seoul Teugbyeolsi [Seoul-T'ukpyolshi]
Country [113] 0 0
South Korea
State/province [113] 0 0
Seoul Teugbyeolsi
Country [114] 0 0
South Korea
State/province [114] 0 0
Seoul
Country [115] 0 0
Spain
State/province [115] 0 0
Balearic Islands
Country [116] 0 0
Spain
State/province [116] 0 0
Barcelona
Country [117] 0 0
Spain
State/province [117] 0 0
Las Palmas
Country [118] 0 0
Spain
State/province [118] 0 0
Madrid
Country [119] 0 0
Spain
State/province [119] 0 0
Tarragona
Country [120] 0 0
Spain
State/province [120] 0 0
Granada
Country [121] 0 0
Spain
State/province [121] 0 0
Lugo
Country [122] 0 0
Spain
State/province [122] 0 0
Málaga
Country [123] 0 0
Spain
State/province [123] 0 0
Seville
Country [124] 0 0
Spain
State/province [124] 0 0
Valencia
Country [125] 0 0
Thailand
State/province [125] 0 0
Bangkok
Country [126] 0 0
Thailand
State/province [126] 0 0
Changwat Lampang
Country [127] 0 0
Thailand
State/province [127] 0 0
Changwat Songkhla
Country [128] 0 0
Thailand
State/province [128] 0 0
Khet Dusit
Country [129] 0 0
Turkey (Türkiye)
State/province [129] 0 0
Adana
Country [130] 0 0
Turkey (Türkiye)
State/province [130] 0 0
Ankara
Country [131] 0 0
Turkey (Türkiye)
State/province [131] 0 0
Diyarbakir
Country [132] 0 0
Turkey (Türkiye)
State/province [132] 0 0
Gaziantep
Country [133] 0 0
Turkey (Türkiye)
State/province [133] 0 0
Istanbul
Country [134] 0 0
Turkey (Türkiye)
State/province [134] 0 0
Manisa
Country [135] 0 0
Turkey (Türkiye)
State/province [135] 0 0
Samsun
Country [136] 0 0
Turkey (Türkiye)
State/province [136] 0 0
Edirne
Country [137] 0 0
Turkey (Türkiye)
State/province [137] 0 0
Izmir
Country [138] 0 0
United Kingdom
State/province [138] 0 0
England
Country [139] 0 0
United Kingdom
State/province [139] 0 0
Wales

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Taiho Oncology, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Taiho Oncology INC
Address 0 0
Country 0 0
Phone 0 0
+1 844-878-2446
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT07128199