A Phase 2, Open-Label, Randomized, Global Study of Three Telisotuzumab Vedotin Regimens in Subjects With Previously Treated c-Met Overexpressing, EGFR Wildtype, Locally Advanced/Metastatic Non-Squamous Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 140
- 主要终点
- Percentage of Participants with Treatment-Emergent Adverse Events (AE)s (Any-grade and Grade >= 2)
研究概览
简要总结
Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. Non-small cell lung cancer (NSCLC) is a solid tumor, a disease in which cancer cells form in the tissues of the lung. The purpose of this study is to assess how safe telisotuzumab vedotin is in adult participants with NSCLC. Change in disease activity and adverse events will be assessed.
Telisotuzumab vedotin is an investigational drug being developed for the treatment of NSCLC. Participants will be randomly assigned a treatment of telisotuzumab vedotin in 1 of 3 arms at an 1:1:1 ratio. Each group receives intravenous (IV) infusion of telisotuzumab vedotin at different doses. Approximately 150 adult participants with c-Met overexpressing NSCLC will be enrolled in the study at approximately 80 to 90 sites worldwide.
Participants will receive IV telisotuzumab vedotin at 1 of 3 dose regimens as part of a 3 year study duration.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
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
- 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
- •Projected life expectancy of at least 12 weeks.
- •Must have c-Met overexpressing non-small cell lung cancer (NSCLC) (defined as >= 25% tumor cells with 3+ staining (high [>= 50% 3+]; intermediate [>= 25% - < 50%]) as assessed by a Sponsor designated immunohistochemistry (IHC) laboratory
- •Must have histologically or cytologically documented NSCLC that is locally advanced or metastatic.
- •Must have a known epidermal growth factor receptor (EGFR) activating mutation status.
- •Actionable alterations in genes other than EGFR are permitted.
- •Must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.
- •Must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to
- •Must have received no more than 1 line of prior systemic cytotoxic chemotherapy in the locally advanced or metastatic setting, as stated in the protocol.
- •Must have progressed on at least 1 line of prior therapy for locally advanced/metastatic NSCLC, as stated in the protocol.
排除标准
- •Adenosquamous or neuroendocrine histology, or sarcomatoid features.
- •EGFR activating mutations (e.g., EGFR Exon 19 deletions, T790M, Exon 21 L858R, or Exon 20 insertion mutations).
- •Received prior c-Met-targeted antibodies, prior telisotuzumab vedotin, or prior antibody-drug conjugates either targeting c-Met or consisting of monomethylauristatin E.
- •Received prior docetaxel therapy.
- •Metastases to the central nervous system (CNS). Participants with CNS metastases are eligible only after adequate treatment (such as surgery or, radiotherapy, or drug therapy) is provided, as stated on the protocol.
- •History of other malignancies except those stated in the protocol.
- •History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan, as noted in the protocol.
- •Unresolved clinically significant adverse event (AE) >= Grade 2 from prior anticancer therapy, except for alopecia or anemia. Participants with hormone deficiencies caused by prior anticancer therapy who are asymptomatic and on a stable dose of replacement hormone are eligible for study.
- •Major surgery within 21 days prior to randomization.
- •Clinically significant condition(s) including but not limited to those listed in the protocol.
- •Clinically significant liver disease, including hepatitis, current alcohol abuse, or cirrhosis.
- •Grade >= 2 edema or lymphedema.
- •Grade >= 2 ascites or pleural effusion.
- •Grade >= 2 neuropathy.
- •Active uncontrolled bacterial or viral infection.
- •Active corneal disorder.
研究组 & 干预措施
Telisotuzumab Vedotin Dose A
Participants will receive telisotuzumab vedotin dose A, as part of the 3 year study duration.
干预措施: Telisotuzumab Vedotin (Drug)
Telisotuzumab Vedotin Dose B
Participants will receive telisotuzumab vedotin dose B, as part of the 3 year study duration.
干预措施: Telisotuzumab Vedotin (Drug)
Telisotuzumab Vedotin Dose C
Participants will receive telisotuzumab vedotin dose C, as part of the 3 year study duration.
干预措施: Telisotuzumab Vedotin (Drug)
结局指标
主要结局
Percentage of Participants with Treatment-Emergent Adverse Events (AE)s (Any-grade and Grade >= 2)
时间窗: Up to Approximately 3 Years
An AE is defined as any untoward medical occurrence, inappropriate participant management decision, unintended disease or injury or any untoward clinical signs (including an abnormal laboratory finding) in participants, users or other persons whether or not related to the investigational medical device.
Percentage of Participants with Treatment-Emergent Interstitial Lung Disease (ILD)
时间窗: Up to Approximately 3 Years
ILD is defined by ILD standardized MedDRA query (SMQ) (broad) per investigator and determined per adjudication (any-grade and Grade \>= 2).
Objective Response (OR) by Blinded Independent Central Review (BICR)
时间窗: Up to Approximately 3 Years
OR will be defined as achieving confirmed complete response (CR) or confirmed partial response (PR) based on response evaluation criteria in solid tumors (RECIST), version 1.1.
Percentage of Participants with Treatment-Emergent Ocular Surface Disorders
时间窗: Up to Approximately 3 Years
Treatment-emergent ocular surface disorders defined by corneal epitheliopathy company MedDRA query (CMQ) (any-grade and Grade \>= 2).
Percentage of Participants with Treatment-Emergent AEs Leading to Study Drug Discontinuation
时间窗: Up to Approximately 3 Years
An AE is defined as any untoward medical occurrence, inappropriate participant management decision, unintended disease or injury or any untoward clinical signs (including an abnormal laboratory finding) in participants, users or other persons whether or not related to the investigational medical device.
Percentage of Participants with Grade 5 Treatment-Emergent AEs
时间窗: Up to Approximately 3 Years
An AE is defined as any untoward medical occurrence, inappropriate participant management decision, unintended disease or injury or any untoward clinical signs (including an abnormal laboratory finding) in participants, users or other persons whether or not related to the investigational medical device.
Percentage of Participants with Treatment-Emergent Peripheral Neuropathy
时间窗: Up to Approximately 3 Years
Peripheral neuropathy is defined by peripheral neuropathy SMQ (narrow) (any-grade and Grade \>= 2)
次要结局
- Progression-Free Survival (PFS) by BICR(Up to Approximately 3 Years)
- Concentrations of Telisotuzumab Vedotin Conjugate in Serum(Up to 26 Weeks)
- Concentrations of Monomethylauristatin E (MMAE) Payload in Plasma(Up to 26 Weeks)
- Percentage of Participants with Antidrug Antibodies (ADAs) of Telisotuzumab Vedotin(Up to 26 Weeks)
- Change in GP5 item of the Functional Assessment of Cancer Therapy-General (FACT-G)(Cycle 1: Day 1, Day 8, Cycle 2 D1 and D1 of Every Even Cycle Thereafter, Through 3 Years)
- Duration of Response (DoR) by BICR(Up to Approximately 3 Years)
- Percentage of Participants with Neutralizing Antidrug Antibodies (nADAs) of Telisotuzumab Vedotin(Up to 26 Weeks)
- Change in Selected items of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)(Cycle 1: Day 1, Day 8, Cycle 2 D1 and D1 of Every Even Cycle Thereafter, Through 3 Years)
- Overall Survival (OS)(Up to Approximately 3 Years)