Randomized, Open-label, Multicenter,Phase 3 Trial of Repotrectinib VersusCrizotinib in Participants with Locally Advanced or Metastatic Tyrosine Kinase Inhibitor (TKI)-naïve ROS1-positive Non-Small Cell Lung Cancer (NSCLC) (TRIDENT-3)
概览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 230
- 试验地点
- 13
- 主要终点
- To compare the PFS per BICR of repotrectinib and crizotinib in all randomized participants with locally advanced or metastatic TKI-naïve ROS1-positive NSCLC
概览
简要总结
The data collected during this study are confidential and proprietary to the Sponsor or designee. Any publications or abstractsarising from this study must adhere to the publication requirements set forth in the Clinical Trial Agreement (CTAg) governing [study site or investigator] participation in the study. These requirements include, but are not limited to, submitting proposedpublications to the Sponsor or designee at the earliest practicable time prior to submission or presentation and otherwise within the period set forth in the CTAg.Scientific publications (such as abstracts, congress podium presentations and posters, and manuscripts) of the study results will be a collaborative effort between the study Sponsor and the external authors. No public presentation or publication of any interim results may be made by any Principal Investigator, sub-investigator,or any other member of the study staff without the prior written consent of the Sponsor.Authorship of publications at the Sponsor is aligned with the criteria of the International Committee of Medical Journal Editors (ICMJE;www.icmje.org). Authorship selection is based on significant contributions to the study (ie, ICMJE criterion #1). Authors must meet all 4 ICMJE criteria for authorship:
1)Substantial intellectual contribution to the conception or design of the work; or the acquisition of data (ie, evaluable participants with quality data), analysis, or interpretation of data for the work(eg, problem solving, advice, evaluation, insights,and conclusion)2)Drafting the work or revising it critically for important intellectual content3)Final approval of the version to be published4)Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolvedThose who make the most significant contributions, as defined above, will be considered by the Sponsor for authorship of the primary publication. Sub-investigators will generally not be considered for authorship in the primary publication. Geographic representation will also be considered.Authors will be listed by order of significant contributions (highest to lowest), with the exception of the last author. Authors in first and last position have provided the most significant contributions to the work. For secondary analyses and related publications, author list and author order may vary from primary to reflect additional contributions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Participant has histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC (Stage IIIB, IIIC, IVA, or IVB per 8th edition American Joint Committee on Cancer classification).
- •Participant has a ROS1 gene rearrangement or fusion as detected by a local test.
- •(Central testing is required if local test is not acceptable by Sponsor-required criteria.)
- •At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), as assessed by the investigator.
- •Participants must not be exposed previously with TKIs that demonstrated activities in ROS1-positive NSCLC (eg, crizotinib, ceritinib, lorlatinib, brigatinib, entrectinib, ensartinib, DS605 1 b, NVL-520, taletrectinib, foretinib, and cabozantinib).
- •Up to 1 prior line of systemic treatment for NSCLC is permitted (chemotherapy-based, immunotherapy-based, chemotherapy + immunotherapy combination regimens, non-ROS1 TKI regimens, or concurrent chemoradiation regimens [when administered in the context of definitive thoracic radiotherapy]).
- •Prior (neo)-adjuvant treatment for resectable NSCLC does not count as a prior line of therapy if no disease recurrence within 6 months of the completion of the (neo)-adjuvant therapy.
- •Eastern Cooperative Oncology Group Performance Status less than equal to 2.
排除标准
- •Symptomatic brain metastases or symptomatic leptomeningeal involvement.
- •History of previous cancer requiring therapy within the previous 2 years, except for NSCLC under study, squamous cell or basal-cell carcinoma of the skin, or any in situ carcinoma that has been completely resected.
- •Known tumor targetable co-mutations or rearrangements (ie, epidermal growth factor receptor [EGFR] or anaplastic lymphoma kinase [ALK]).
- •Clinically significant cardiovascular disease (either active or within 6 months prior to enrollment): myocardial infarction, unstable angina, coronary or peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association Classification Class more than II), cerebrovascular accident or transient ischemic attack, symptomatic bradycardia, requirement for anti-arrhythmic medication.
- •Ongoing cardiac dysrhythmias of Common Terminology Criteria of Adverse Events version 5.0 Grade more than equal to 2.
结局指标
主要结局
To compare the PFS per BICR of repotrectinib and crizotinib in all randomized participants with locally advanced or metastatic TKI-naïve ROS1-positive NSCLC
时间窗: Until disease progression,death, or end of study (up to 5 years or time of final OS analysis[approximately 130events]), whichever occurs earlier.
次要结局
- To compare the OS of repotrectinib & crizotinib in all randomized participants with locally advanced or metastatic TKI-naïve ROS1-positive NSCLC(Up to 5 years from last participants randomized, or until the time of final OS analysis(approximately 130events), whichever occurs later.)
- To assess the tumor response of repotrectinib & crizotinib in all randomized participants with locally advanced or metastatic TKI-naïve ROS1-positive NSCLC(Until disease progression, death, or end of study (up to 5 years or time of final OS analysis[approximately 130events]), whichever occurs earlier.)
- To assess the PFS per investigator of repotrectinib & crizotinib in all randomized participants with locally advanced or metastatic TKI-naïve ROS1-positive NSCLC(Until disease progression, death, or end of study (up to 5 years or time of final OS analysis[approximately 130events]), whichever occurs earlier.)
- To assess time to intracranial progression of repotrectinib & crizotinib in all randomized participants with locally advanced or metastatic TKI-naïve ROS1-positive NSCLC(Until disease progression, death, or end of study (up to 5 years or time of final OS analysis[approximately 130events]), whichever occurs earlier.)
- To assess the safety of repotrectinib and crizotinib in all treated participants with locally advanced or metastatic TKI-naïve ROS1-positive NSCLC(Incidence of AEs, SAEs, AEs leading to study intervention discontinuation, drug-related AEs, and deaths)
- To assess disease-related symptoms for repotrectinib and crizotinib in all randomized participants with locally advanced or metastatic TKI-naïve ROS1-positive NSCLC(Proportion of participants without meaningful symptom deterioration (at least 3-point change) as measured by the NSCLC-SAQ total score)
研究者
Shilpi Sinha
Bristol Myers Squibb India Pvt. Ltd.