RECRUITING

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

Conditions

NSCLC, Stage IB-IIIA Lung Cancer Adjuvant Post-surgical EGFR Exon 20 Early Stage Lung Cancer Uncommon EGFR Mutations

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to compare the efficacy of zipalertinib combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in participants with early stage (stage IB-IIIA) resected non-small cell lung cancer (NSCLC) harboring uncommon epidermal growth factor receptor mutation (EGFRmt).

Official 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)

Quick Facts

Study Start:2025-08-28

Study Completion:2032-10

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT07128199

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	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: 11. Is unable or unwilling to take dexamethasone, folic acid, and/or vitamin B12 supplementation during treatment with pemetrexed.

Inclusion Criteria

Exclusion 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.

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:
11. Is unable or unwilling to take dexamethasone, folic acid, and/or vitamin B12 supplementation during treatment with pemetrexed.

Contacts and Locations

Study Contact

Taiho Oncology INC

CONTACT

+1 844-878-2446

medicalinformation@taihooncology.com

Study Locations (Sites)

Alaska Oncology and Hematology

Anchorage, Alaska, 99508

United States

City of Hope Comprehensive Cancer Center - Duarte

Duarte, California, 91010

United States

Georgetown University School of Medicine

Washington D.C., District of Columbia, 20007

United States

D&H Cancer Research Center - Margate

Margate, Florida, 33063

United States

Alpha Oncology Research

Orange City, Florida, 32763

United States

University of Illinois Medical Center

Chicago, Illinois, 60612

United States

Profound Research LLC at Michigan Hematology and Oncology Consultants

Dearborn, Michigan, 48126

United States

Henry Ford Health System

Detroit, Michigan, 48202

United States

Perlmutter Cancer Center - 34th Street

New York, New York, 10016

United States

Memorial Sloan Kettering Cancer Center - New York

New York, New York, 10065

United States

Atrium Health Wake Forest Baptist - Comprehensive Cancer Center

Charlotte, North Carolina, 28204

United States

Gabrail Cancer and Research Center

Canton, Ohio, 44718

United States

Virginia Cancer Specialists - Fairfax Office

Fairfax, Virginia, 22031

United States

Collaborators and Investigators

Sponsor: Taiho Oncology, Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-08-28

Study Completion Date2032-10

Study Record Updates

Study Start Date2025-08-28

Study Completion Date2032-10

Terms related to this study

Additional Relevant MeSH Terms

NSCLC, Stage IB-IIIA
Lung Cancer
Adjuvant
Post-surgical
EGFR
Exon 20
Early Stage Lung Cancer
Uncommon EGFR Mutations