Zipalertinib vs placebo after surgery for uncommon EGFR-mutant NSCLC

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

In this phase 3 trial, participants with resected non-small cell lung cancer carrying uncommon EGFR mutations are randomized to zipalertinib twice daily or placebo for a defined period. An independent data monitoring committee will review safety data during the study. Eligibility includes confirmed non-squamous NSCLC, specific uncommon EGFR mutations, no brain metastases, complete surgical resection with negative margins, and adequate recovery from surgery. The study aims to determine if the EGFR inhibitor can reduce the risk of cancer returning after surgery. Approximately 360 participants will be enrolled across multiple sites.

Why it matters

Who can join: the full rules

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.

Where it's running

• Alaska Oncology and Hematology
  Anchorage, Alaska, United States Recruiting
• Georgetown University School of Medicine
  Washington D.C., District of Columbia, United States Recruiting
• D&H Cancer Research Center - Margate
  Margate, Florida, United States Recruiting
• Alpha Oncology Research
  Orange City, Florida, United States Recruiting
• University of Illinois Medical Center
  Chicago, Illinois, United States Recruiting
• Profound Research LLC at Michigan Hematology and Oncology Consultants
  Dearborn, Michigan, United States Recruiting

+203 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: Taiho Oncology, Inc.
• Email: medicalinformation@taihooncology.com
• Phone: +1 844-878-2446

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Stereotactic Body Proton Therapy for Early-Stage Lung Cancer in Inoperable or Surgery-Refusing Patients

  This study tests whether high-precision proton therapy given in few sessions can treat early-stage non-small cell lung cancer in patients who cannot have surgery or won’t have it.

  Recruiting Guangzhou Concord Cancer Center · Guangzhou, Guangdong · NCT07412327

• ePRO in advanced lung cancer: emotional distress, brain metastasis, and symptom burden

  This study tests how patients with advanced lung cancer—some with brain metastases—report emotional distress and symptoms over time using electronic questionnaires.

  Recruiting Tongji Hospital · Hubei, Wuhan · NCT07912190

• Urine VOC Test to Detect Lung Cancer in Never Smokers

  A urine test that looks for volatile compounds is tested to see if it can help detect lung cancer in adults who have never smoked.

  Recruiting Thomas Jefferson University · Philadelphia, Pennsylvania · NCT07871656

• SI-B036 safety test in advanced and metastatic solid tumors

  This early-phase study checks whether SI-B036 is safe and tolerable in adults with advanced or metastatic solid cancers who have had prior therapy.

  Recruiting at 4 sites Phase 1 SystImmune Inc. · New Haven, Connecticut and 6 other locations · NCT07857616

• Guaraná Supplement for Cancer-Related Fatigue in People Undergoing Treatment

  This study tests whether taking guaraná capsules helps reduce cancer-related fatigue and improve quality of life in adults with breast, lung, colorectal, or gastric cancer who are actively receiving treatment.

  Recruiting Centro de Tratamiento e Investigación sobre Cáncer, Luis Carlos Sarmiento Angulo · Bogotá, Bogota D.C. · NCT07816263

• ENPP1/cGAS and FAP in Solid Tumors in Vietnamese Patients

  This Vietnam-based study will test ENPP1, cGAS, and FAP expression in archived tumor samples from Vietnamese adults with solid cancers using immunohistochemistry.

  Recruiting at 2 sites Tam Anh Research Institute · Hanoi, Hanoi and 1 other locations · NCT07808164

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.