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)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 360
- 试验地点
- 425
- 主要终点
- Disease-free Survival (DFS) as Assessed by the Investigator
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •exon20 insertion mutations (ex20ins) or
- •other uncommon, non-ex20ins EGFRmt (eg, G719X, L861Q, or S768I) exons 18-21 of the EGFR tyrosine kinase domain
- •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:
- •For participants without prior adjuvant chemotherapy: 4 weeks and 12 weeks following surgery.
- •For participants with prior adjuvant chemotherapy: 4 weeks and 8 weeks after the last dose of adjuvant chemotherapy.
- •Eastern cooperative oncology group performance status (ECOG PS) of 0 or
- •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 N
- •Archival tumor tissue available for submission, with minimum quantity sufficient to evaluate EGFRmt status and, where possible, other biomarkers.
排除标准
- •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:
- •Zipalertinib (TAS6417/CLN-081) or any other EGFR inhibitor at any time.
- •Pre-operative or post-operative or planned radiation therapy for the current lung cancer.
- •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)
- •Major surgery (including primary tumor surgery, excluding placement of vascular access) within 4 weeks prior to the first dose of study treatment.
- •Treatment with an investigational drug within five half-lives of the compound or any of its related material, if known.
- •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:
- •Non-melanoma skin cancer treated with curative intent
- •Carcinoma in situ treated with curative intent
- •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.
- •Concurrent malignancy of which natural history does not have the potential to interfere with the safety or efficacy assessment (eg, Gleason 6 prostate cancer)
- •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.
研究组 & 干预措施
Placebo
Participants will receive adjuvant platinum-based chemotherapy consisting of cisplatin or carboplatin plus pemetrexed, administered via IV infusion, in combination with zipalertinib matching-placebo.
After completion of chemotherapy, participants will continue on zipalertinib matching-placebo, until the participant meets any of the treatment discontinuation criteria.
干预措施: Zipalertinib Matching-placebo (Drug)
Zipalertinib
Participants will receive adjuvant platinum-based chemotherapy consisting of cisplatin or carboplatin plus pemetrexed, administered via intravenous (IV) infusion, in combination with zipalertinib.
After completion of chemotherapy, participants will continue on zipalertinib monotherapy, orally, until the participant meets any of the treatment discontinuation criteria.
干预措施: Carboplatin (Drug)
Zipalertinib
Participants will receive adjuvant platinum-based chemotherapy consisting of cisplatin or carboplatin plus pemetrexed, administered via intravenous (IV) infusion, in combination with zipalertinib.
After completion of chemotherapy, participants will continue on zipalertinib monotherapy, orally, until the participant meets any of the treatment discontinuation criteria.
干预措施: TAS6417 (Drug)
Placebo
Participants will receive adjuvant platinum-based chemotherapy consisting of cisplatin or carboplatin plus pemetrexed, administered via IV infusion, in combination with zipalertinib matching-placebo.
After completion of chemotherapy, participants will continue on zipalertinib matching-placebo, until the participant meets any of the treatment discontinuation criteria.
干预措施: Cisplatin (Drug)
Zipalertinib
Participants will receive adjuvant platinum-based chemotherapy consisting of cisplatin or carboplatin plus pemetrexed, administered via intravenous (IV) infusion, in combination with zipalertinib.
After completion of chemotherapy, participants will continue on zipalertinib monotherapy, orally, until the participant meets any of the treatment discontinuation criteria.
干预措施: Pemetrexed (Drug)
Zipalertinib
Participants will receive adjuvant platinum-based chemotherapy consisting of cisplatin or carboplatin plus pemetrexed, administered via intravenous (IV) infusion, in combination with zipalertinib.
After completion of chemotherapy, participants will continue on zipalertinib monotherapy, orally, until the participant meets any of the treatment discontinuation criteria.
干预措施: Cisplatin (Drug)
Placebo
Participants will receive adjuvant platinum-based chemotherapy consisting of cisplatin or carboplatin plus pemetrexed, administered via IV infusion, in combination with zipalertinib matching-placebo.
After completion of chemotherapy, participants will continue on zipalertinib matching-placebo, until the participant meets any of the treatment discontinuation criteria.
干预措施: Carboplatin (Drug)
Placebo
Participants will receive adjuvant platinum-based chemotherapy consisting of cisplatin or carboplatin plus pemetrexed, administered via IV infusion, in combination with zipalertinib matching-placebo.
After completion of chemotherapy, participants will continue on zipalertinib matching-placebo, until the participant meets any of the treatment discontinuation criteria.
干预措施: Pemetrexed (Drug)
结局指标
主要结局
Disease-free Survival (DFS) as Assessed by the Investigator
时间窗: Up to 5 years
次要结局
- Change From Baseline in European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) Scores(Up to 5 years)
- Disease-free Survival Rate(Up to 5 years)
- Overall Survival Rate(Up to 5 years)
- Disease-free Survival Rate(At 2, 3 and 5 years)
- Overall Survival (OS)(Up to 5 years)
- Overall Survival Rate(At 2, 3 and 5 years)
- DFS of Central Nervous System (cDFS)(Up to 5 years)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0)(Up to 5 years)
- Number of Participants with Clinically Significant Changes in Clinical Laboratory Parameters(Up to 5 years)
- Number of Participants with Clinically Significant Changes in Vital Signs(Up to 5 years)
- Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Parameters(Up to 5 years)
- Number of Participants With Change in Left Ventricular Ejection Fraction (LVEF) Evaluated Using Electrocardiography (ECHO) and Multigated Acquisition (MUGA) Scan(Up to 5 years)
- Change in EuroQuality of Life-5 Dimensional 3-Level (EQ-5D-3L)(Baseline, up to 5 years)
- Change From Baseline in European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) Scores(Up to 5 years)