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).
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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) exons 18-21 of the EGFR tyrosine kinase domain
3. 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
4. Complete surgical resection of the primary NSCLC is mandatory with negative surgical margins and systematic lymph node sampling or dissection.
5. 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:
1. For participants without prior adjuvant chemotherapy: 4 weeks and 12 weeks following surgery.
2. For participants with prior adjuvant chemotherapy: 4 weeks and 8 weeks after the last dose of adjuvant chemotherapy.
6. Eastern cooperative oncology group performance status (ECOG PS) of 0 or 1.
7. 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.
8. Archival tumor tissue available for submission, with minimum quantity sufficient to evaluate EGFRmt status and, where possible, other biomarkers.
Exclusion Criteria:
1. Is currently receiving an investigational drug in a clinical trial or participating in any other type of medical research.
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 for NSCLC, including preoperative (neoadjuvant) chemotherapy, immunotherapy, or investigational therapy. (Exception: Participants who have received postoperative adjuvant platinum-based chemotherapy up to 4 cycles are permitted)
4. Major surgery (including primary tumor surgery, excluding placement of vascular access) within 4 weeks prior to the first dose of study treatment.
5. Treatment with an investigational drug within five half-lives of the compound or any of its related material, if known.
3. Has received only wedge resections (complete anatomic segmentectomy is acceptable).
4. Past medical history of interstitial lung disease (ILD)/pneumonitis, drug-induced ILD/pneumonitis or any evidence of clinically active ILD/pneumonitis.
5. 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).
6. Has a history of any other cancer except for any of the following:
1. Non-melanoma skin cancer treated with curative intent
2. Carcinoma in situ treated with curative intent
3. Other curatively treated cancer, with no evidence of disease for \>3 years following the end of treatment and, in the opinion of the treating physician, has no substantial risk of recurrence.
4. Concurrent malignancy of which natural history does not have the potential to interfere with the safety or efficacy assessment (eg, Gleason 6 prostate cancer)
7. Known history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) that is unstable or not controlled with treatment.
8. Active bleeding disorders.
9. Known hypersensitivity to the ingredients in zipalertinib/placebo or any drugs similar in structure or class.
Primary outcome measure(s)
Disease-free Survival (DFS) as Assessed by the Investigator — Up to 5 years
Trial sites (252)
Facility
City
Region
Status
Alaska Oncology and Hematology
Anchorage
Alaska
City of Hope Comprehensive Cancer Center - Duarte
Duarte
California
City of Hope Comprehensive Cancer Center Orange County Lennar Foundation Cancer Center
Irvine
California
Scripps Clinic Torrey Pines
La Jolla
California
Kaiser Permanente - Vallejo Medical Center
Vallejo
California
Georgetown University School of Medicine
Washington D.C.
District of Columbia
D&H Cancer Research Center - Margate
Margate
Florida
Alpha Oncology Research
Orange City
Florida
City of Hope - Atlanta
Newnan
Georgia
University of Illinois Medical Center
Chicago
Illinois
Profound Research LLC at Michigan Hematology and Oncology Consultants
Dearborn
Michigan
Henry Ford Health System
Detroit
Michigan
Memorial Sloan Kettering Cancer Center - Basking Ridge
Basking Ridge
New Jersey
Memorial Sloan Kettering Cancer Center - Monmouth
Middletown
New Jersey
Memorial Sloan Kettering Cancer Center - Bergen
Montvale
New Jersey
Memorial Sloan Kettering Cancer Center - Commack
Commack
New York
Memorial Sloan Kettering Cancer Center - Westchester
East White Plains
New York
Long Island Jewish Medical Center
Lake Success
New York
Perlmutter Cancer Center - 34th Street
New York
New York
Memorial Sloan Kettering Cancer Center - New York
New York
New York
Memorial Sloan Kettering Cancer Center - Nassau
Uniondale
New York
Atrium Health Wake Forest Baptist - Comprehensive Cancer Center
Charlotte
North Carolina
Durham Veterans Affairs Health Care System
Durham
North Carolina
Gabrail Cancer and Research Center
Canton
Ohio
Gibbs Cancer Center and Research Institute Spartanburg
Spartanburg
South Carolina
Virginia Cancer Specialists - Arlington Office
Arlington
Virginia
Virginia Cancer Specialists - Fairfax Office
Fairfax
Virginia
Virginia Cancer Specialists - Bristow Office
Manassas
Virginia
Virginia Cancer Specialists - Reston
Reston
Virginia
Virginia Cancer Specialists - Woodbridge Office
Woodbridge
Virginia
Instituto Argentino de Diagnóstico y Tratamiento
Ciudad Autónoma de Buenos Aires
Buenos Aires
Centro de Investigación Pergamino SA
Pergamino
Buenos Aires
Hospital Universitario Austral
Pilar
Buenos Aires
CEMAIC - Centro de Especialidades Médicas Ambulatorias e Investigación Clínica
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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