A Phase 3, Randomized, Open-label Trial Comparing VT3989 Versus Gemcitabine or Vinorelbine in Participants With Advanced Epithelioid Mesothelioma, Who Previously Received Platinum-Based Systemic Chemotherapy and Immunotherapy
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 350
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
This randomized, open-label, multicenter Phase 3 trial will compare VT3989 with Investigator's choice of gemcitabine or vinorelbine in adults with advanced epithelioid pleural mesothelioma whose disease progressed after prior platinum-based systemic chemotherapy and immunotherapy.
详细描述
Approximately 350 participants will be randomized 1:1 to VT3989 (Arm A) or Investigator's choice chemotherapy with gemcitabine or vinorelbine (Arm B).
VT3989 will be administered orally at 100 mg once daily for 2 weeks on treatment followed by 2 weeks off treatment in each 4-week cycle. Comparator treatment will be gemcitabine or vinorelbine using the protocol-specified regimen or local prescribing/institutional practice.
The trial includes screening, treatment, safety follow-up, and survival follow-up periods. A QTc Sub-Study will evaluate cardiac repolarization using time-matched pharmacokinetic samples and ECGs in approximately 25 Arm A participants. Overall survival is the primary endpoint; BICR-assessed progression-free survival is the key secondary endpoint.
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
- •Male or female, age 18 years or older at informed consent.
- •Pathologically confirmed advanced epithelioid pleural mesothelioma previously treated with platinum-based systemic chemotherapy and immunotherapy, given sequentially or concurrently.
- •Radiologically measurable disease by modified RECIST v1.1 or RECIST v1.
- •Adequate organ functions, including the liver, kidneys, and hematopoietic system.
排除标准
- •Active brain metastases or primary CNS (central nervous system) tumors.
- •History of leptomeningeal metastases
- •Active or chronic, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
- •Known HIV positive or active Hepatitis B or Hepatitis C
- •Clinically significant cardiovascular disease and prior exposure to cardiotoxic agents
- •Corrected QT (QTcF) interval > 470 msec (using Fridericia's correction formula).
- •Women who are pregnant or breastfeeding
- •Non-pleural mesothelioma at initial diagnosis or an aggressive histologic type such as sarcomatoid or biphasic mesothelioma.
- •Prior treatment with a TEAD inhibitor, including VT3989 or another agent targeting the same molecular pathway.
- •Prior receipt of both comparator treatments, gemcitabine and vinorelbine, alone or in combination, or known hypersensitivity to both. A participant who received only one comparator may enroll but must not be assigned to that same comparator.
研究组 & 干预措施
Arm A - VT3989
VT3989 monotherapy in 28-day cycles until BICR-verified progression, unacceptable toxicity, withdrawal, or another protocol-specified reason.
干预措施: VT3989 (Drug)
Arm B - Investigator's Choice Chemotherapy
The Investigator selects 21-day cycle of gemcitabine or vinorelbine. Administration and dose modification may follow the protocol, local prescribing information, or institutional practice.
干预措施: Vinorelbine (Drug)
Arm B - Investigator's Choice Chemotherapy
The Investigator selects 21-day cycle of gemcitabine or vinorelbine. Administration and dose modification may follow the protocol, local prescribing information, or institutional practice.
干预措施: gemcitabine (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: Approximately 32-35 months after first randomization
Time from randomization to death from any cause. Participants without an observed death will be censored at the last date known alive or the analysis cut-off date, whichever is earlier.
次要结局
- Progression-Free Survival by BICR(From randomization through radiologic progression, death, up to approximately 3 years or more)
- Treatment-Emergent Adverse Events and Serious Adverse Events(From first dose through the safety follow-up visit, (28 days after the last dose), up to approximately 3 years or more.)
- Disease-related symptoms and health-related quality of life outcomes(Baseline through treatment and protocol-specified follow-up; up to approximately 3 years or more)
- Overall Response Rate by BICR(Tumor assessments during treatment and applicable follow-up; up to approximately 3 years or more)
- Duration of Response(From first documented response through progression, death, or analysis cut-off; up to approximately 3 years or more)
- Disease Control Rate by BICR(Tumor assessments during treatment and applicable follow-up; up to approximately 3 years or more)
- Time to Response(From randomization to first documented response; up to approximately 3 years or more)
- EORTC QLQ-LC13(Baseline through treatment and protocol-specified follow-up; up to approximately 3 years or more)
- EQ-5D-5L(Baseline through treatment and protocol-specified follow-up; up to approximately 3 years or more)
- Time to Deterioration(From baseline/randomization through protocol-defined deterioration; up to approximately 3 years or more)