A Phase 2b, Open-Label, Two-cohort Study of Subcutaneous Amivantamab in Combination With Lazertinib as First-Line Treatment, or Subcutaneous Amivantamab in Combination With Platinum-Based Chemotherapy as Second-line Treatment, for Common EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 480
- 试验地点
- 210
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
The primary purpose of the study is to assess how well amivantamab in combination with lazertinib or in combination with chemotherapy works (antitumor activity) in participants with epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (NSCLC; that is one of the major types of lung cancer).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- •Have histologically or cytologically confirmed advanced or metastatic non-small cell lung cancer (NSCLC) that is not amenable to curative intent therapy
- •Epidermal growth factor resistance-mutation (EGFRm) must be an Ex19del or Ex21 L858R substitution, as detected by food and drug administration (FDA)-approved or other validated test in a clinical laboratory improvement amendments (CLIA)-certified laboratory (sites in the US), or an accredited local laboratory (sites outside of the US) in accordance with site standard of care. In the European union (EU), the local test must be Conformité Européenne (CE)-marked or an in-house laboratory-developed test from health institutions in the EU in accordance with Article 5(5) of the in vitro diagnostic regulations (IVDR ) 2071/746, as amended
- •Have at least 1 measurable lesion, according to RECIST version (v)1.1, that has not been previously irradiated
- •Any toxicities from prior systemic anticancer therapy must have resolved to national cancer institute common terminology criteria for adverse events (NCI-CTCAE) version 5.0 grade 1 or baseline level (except for alopecia [any grade], grade <=2 peripheral neuropathy, or grade <=2 hypothyroidism stable on hormone replacement)
- •Have an eastern cooperative oncology group (ECOG) performance status of 0 to 1
排除标准
- •Medical history of active interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis. Participants with medical history of radiation pneumonitis, including radiation pneumonitis which required steroid treatment, should consult with the medical monitor and eligibility be assessed on a case-by-case basis
- •Had major surgery excluding placement of vascular access or tumor biopsy or had significant traumatic injury within 4 weeks before the first dose of anticancer treatments or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study
- •Participant has uncontrolled tumor-related pain (symptomatic lesions amenable to palliative radiotherapy should be treated prior to first dosing)
- •Received an investigational treatment that has not been cleared (based on at least 5 half lives of any pharmaceutical treatment) before the planned first dose of study treatment or is currently enrolled in an investigational study
- •Has a prior or concurrent second malignancy (other than the disease under study) which natural history or treatment could likely interfere with any study endpoints of safety or the efficacy of the study treatment(s)
研究组 & 干预措施
Cohort 2: Amivantamab and Chemotherapy
Participants will receive Amivantamab in combination with chemotherapy (carboplatin and pemetrexed) intravenous (IV) infusion in 21-day cycles until disease progression, withdrawal of consent, death, or the investigator decides to discontinue treatment, whichever comes first.
干预措施: Chemotherapy: Pemetrexed (Drug)
Cohort 2: Amivantamab and Chemotherapy
Participants will receive Amivantamab in combination with chemotherapy (carboplatin and pemetrexed) intravenous (IV) infusion in 21-day cycles until disease progression, withdrawal of consent, death, or the investigator decides to discontinue treatment, whichever comes first.
干预措施: Chemotherapy: Carboplatin (Drug)
Cohort 1: Amivantamab and Lazertinib
Participants will receive Amivantamab in combination with Lazertinib orally in 28-day cycles until disease progression, withdrawal of consent, death, or the investigator decides to discontinue treatment, whichever comes first.
干预措施: Amivantamab (Drug)
Cohort 2: Amivantamab and Chemotherapy
Participants will receive Amivantamab in combination with chemotherapy (carboplatin and pemetrexed) intravenous (IV) infusion in 21-day cycles until disease progression, withdrawal of consent, death, or the investigator decides to discontinue treatment, whichever comes first.
干预措施: Amivantamab (Drug)
Cohort 1: Amivantamab and Lazertinib
Participants will receive Amivantamab in combination with Lazertinib orally in 28-day cycles until disease progression, withdrawal of consent, death, or the investigator decides to discontinue treatment, whichever comes first.
干预措施: Lazertinib (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Up to 4 Years and 6 months
PFS is defined as the time from the date of first dose of any study treatment until the date of objective disease progression or death, whichever occurs first according to response evaluation criteria in solid tumors (RECIST) version (v) 1.1 as assessed by the investigator.
Progression Free Survival (PFS)
时间窗: Up to 4 Years and 6 months
PFS is defined as the time from the date of first dose of any study treatment until the date of objective disease progression or death, whichever occurs first according to response evaluation criteria in solid tumors (RECIST) version (v) 1.1 as assessed by the investigator.
次要结局
- Number of Participants Reporting Dose Reductions, Interruptions, and Discontinuations(Up to 4 Years and 6 months)
- Number of Participants With Venous Thromboembolic Events (VTEs)(Up to 4 Years and 6 months)
- Number of Participants With Dermatologic Adverse Events (AEs)(Up to 4 Years and 6 months)
- Number of Participants with AEs by Severity(Up to 4 Years and 6 months)
- Overall Survival (OS)(Up to 4 Years and 6 months)
- Overall Response Rate (ORR)(Up to 4 Years and 6 months)
- Clinical Benefit Rate (CBR)(Up to 4 Years and 6 months)
- Time to Subsequent Therapy (TTST)(Up to 4 Years and 6 months)
- Time to Symptomatic Progression (TTSP)(Up to 4 Years and 6 months)
- Number of Participants Reporting Dose Reductions, Interruptions, and Discontinuations(Up to 4 Years and 6 months)
- Number of Participants With Venous Thromboembolic Events (VTEs)(Up to 4 Years and 6 months)
- Number of Participants With Dermatologic Adverse Events (AEs)(Up to 4 Years and 6 months)
- Number of Participants with AEs by Severity(Up to 4 Years and 6 months)
- Overall Survival (OS)(Up to 4 Years and 6 months)
- Overall Response Rate (ORR)(Up to 4 Years and 6 months)
- Clinical Benefit Rate (CBR)(Up to 4 Years and 6 months)
- Duration of Response (DOR)(Up to 4 Years and 6 months)
- Time to Treatment Discontinuation (TTTD)(Up to 4 Years and 6 months)
- Time to Subsequent Therapy (TTST)(Up to 4 Years and 6 months)
- Time to Symptomatic Progression (TTSP)(Up to 4 Years and 6 months)