A Randomized, Placebo-Controlled, Double-Blind, Multi-Center Phase 3 Study of Zipalertinib Versus Placebo in Early Stage NSCLC Patients With Uncommon EGFR Mutations Following Complete Tumor Resection (REZILIENT4)
A Randomized, Placebo-Controlled, Double-Blind, Multi-Center Phase 3 Study of Zipalertinib Versus Placebo in Early Stage NSCLC Patients With Uncommon EGFR Mutations Following Complete Tumor Resection (REZILIENT4)
The purpose of this study is to compare the efficacy of zipalertinib versus placebo in participants with early stage resected non-small cell lung cancer (NSCLC) harboring uncommon epidermal growth factor receptor mutation (EGFRmt).
This study will evaluate zipalertinib, a novel EGFR tyrosine kinase inhibitor (TKI) versus placebo in participants with resected early stage NSCLC harboring uncommon EGFRmt.
Approximately 360 participants will be randomized to:
Arm A: Zipalertinib twice daily (BID) monotherapy OR
Arm B: Placebo BID monotherapy.
An independent data monitoring committee (IDMC) will be established to monitor interim safety data.
Inclusion Criteria:
Histologically confirmed diagnosis of primary NSCLC on predominantly non-squamous histology.
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:
Baseline imaging assessment of the brain (MRI [preferred modality] or CT scan) performed within 8 weeks prior to randomization must show no evidence of brain metastasis
Complete surgical resection of the primary NSCLC is mandatory with negative surgical margins and systematic lymph node sampling or dissection.
Complete recovery from surgery, including post-operative wound healing, and prior adjuvant chemotherapy (if applicable) at the time of randomization. Randomization timing is defined as follows:
Eastern cooperative oncology group performance status (ECOG PS) of 0 or 1.
Pathologic (post-operative) Stage IB, IIA, IIB, or IIIA according to the AJCC 9th tumor nodes metastasis (TNM) staging system for lung cancer. In addition, participants with stage IIIB are eligible when regional lymph node involvement is N2.
Archival tumor tissue available for submission, with minimum quantity sufficient to evaluate EGFRmt status and, where possible, other biomarkers.
Exclusion Criteria:
Is currently receiving an investigational drug in a clinical trial or participating in any other type of medical research.
Treatment with any of the following within the time frame specified:
Has received only wedge resections (complete anatomic segmentectomy is acceptable).
Past medical history of interstitial lung disease (ILD)/pneumonitis, drug-induced ILD/pneumonitis or any evidence of clinically active ILD/pneumonitis.
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).
Has a history of any other cancer except for any of the following:
Known history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) that is unstable or not controlled with treatment.
Active bleeding disorders.
Known hypersensitivity to the ingredients in zipalertinib/placebo or any drugs similar in structure or class.
Irvine, California 92618, United States
Dearborn, Michigan 48126, United States
Basking Ridge, New Jersey 07920, United States
East White Plains, New York 10604, United States
Charlotte, North Carolina 28204, United States
Spartanburg, South Carolina 29303, United States
Ciudad Autónoma de Buenos Aires, Buenos Aires C1122, Argentina
Córdoba, Córdoba Province X5008HHW, Argentina
Cachoeiro de Itapemirim, Espírito Santo 29308-065, Brazil
Centro Santa Maria, Rio Grande do Sul 97015-450, Brazil
Porto Alegre, Rio Grande do Sul 90050-170, Brazil
Porto Alegre, Rio Grande do Sul 90440-010, Brazil
Porto Alegre, Rio Grande do Sul 91210-250, Brazil
Joinville, Santa Catarina 89201-260, Brazil
Barretos, São Paulo 14784-400, Brazil
Saint-Herblain, Loire-Atlantique 44800, France
Athens, Central Macedonia 54622, Greece
Alessandria, Alessandria 15121, Italy
Bologna, Bologna 40138, Italy
Catania, Catania 95125, Italy
Milan, Milan 20132, Italy
Milan, Milan 20141, Italy
Milan, Milan 20162, Italy
Siena, Siena 53100, Italy
Kurume-Shi, Fukuoka 830-0011, Japan
Osaka, Osaka 541-8567, Japan
Osakasayama-Shi, Osaka 589-8511, Japan
Hidaka-Shi, Saltama 350-1298, Japan
Sunto-gun, Sizuoka [Shizuoka] 411-8777, Japan
Kashiwa-shi, Tiba [Chiba] 277-8577, Japan
Koto, Tokyo 135-8550, Japan
Shinjuku-ku, Tokyo 160-0023, Japan
Pulau Pinang, Pulau Pinang 10450, Malaysia
Selangor Darul Ehsan, 47500, Malaysia
Mirador, Puebla 72530, Mexico
San Isidro, Lima region 15036, Peru
Olsztyn, Warmian-Masurian Voivodeship 10-357, Poland
Bucharest, Bucharest 022328, Romania
Daegu, Daegu Gwang'Yeogsi [Taegu-Kwangyokshi] 41404, South Korea
Hwasun-gun, Jeollanam-do 58128, South Korea
Seoul, Seoul 07061, South Korea
Seoul, Seoul Teugbyeolsi [Seoul-T'Ukpyolshi] 06591, South Korea
Las Palmas de Gran Canaria, Las Palmas 35016, Spain
Bangkoknoi, Bangkok 10700, Thailand
Muang, Changwat Lampang 10400, Thailand
Bangkok, Khet Dusit 10300, Thailand
Yüreğir, Adana 01250, Turkey (Türkiye)
Etlik, Ankara 06010, Turkey (Türkiye)
Şehitkamil, Gaziantep 27310, Turkey (Türkiye)
Istanbul, Istanbul 34722, Turkey (Türkiye)
Atakum, Samsun 55200, Turkey (Türkiye)