RecruitingPhase 3

A Study to Assess Zipalertinib Versus Placebo in Participants With Early Stage NSCLC With Uncommon EGFR Mutations, Following Complete Tumor Resection

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)

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study compares zipalertinib with a placebo, a pill with no active drug. It is for people with early-stage non-small cell lung cancer (NSCLC) with uncommon changes in the EGFR gene who have had their tumor fully removed by surgery.

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).

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • A tissue test confirms NSCLC that is mostly the non-squamous type.
  • Testing at a certified or accredited lab shows an EGFR exon 20 insertion or another uncommon EGFR change in exons 18–21.
  • A brain MRI or CT scan within 8 weeks before study group assignment shows no cancer spread to the brain.
  • Surgery removed all of the tumor, with no cancer at the edges of the removed tissue. Nearby lymph nodes were sampled or removed.
  • You have fully healed from surgery and recovered from any chemotherapy after surgery. Study group assignment must be 4–12 weeks after surgery if you had no chemotherapy, or 4–8 weeks after your last chemotherapy dose.
  • You can do all normal activities or have limits only with hard physical activity.
  • The cancer stage after surgery is IB, IIA, IIB, or IIIA. Stage IIIB also qualifies if nearby lymph node spread is classed as N2.
  • Stored tumor tissue is available in an amount large enough to test for EGFR changes.

Who can't join

  • You are taking part in other medical research or receiving an experimental drug. Recent experimental drug use may also exclude you, depending on how long the drug stays in the body.
  • You have ever taken zipalertinib or another EGFR-blocking drug; had or plan radiation for this lung cancer; or had other whole-body cancer treatment for NSCLC. Up to 4 cycles of platinum-based chemotherapy after surgery are allowed.
  • You had major surgery within 4 weeks before the first study dose, except surgery to place a line into a blood vessel. You had only wedge surgery, which removes a small wedge of lung; removal of a full lung segment is allowed.
  • You have or have had interstitial lung disease or pneumonitis, conditions that cause lung scarring or inflammation.
  • You cannot swallow tablets or have a condition or past bowel surgery that may keep your body from absorbing zipalertinib well.
  • You have a history of another cancer, with exceptions: certain treated skin cancers; treated cancers that stayed where they started; cancers treated to cure with no disease for over 3 years and low risk of returning; or a current cancer that would not affect study safety or results.
  • You have hepatitis B, hepatitis C, or HIV that is unstable or not controlled with treatment, or you have an active bleeding disorder.
  • You have a known allergy to ingredients in zipalertinib or the placebo, or to similar drugs.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

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.

Study sites (30)

AK

CA

DC

FL

GA

IL

MI

NC

NJ

NY

OH

SC

VA