Phase I/II, Multi-Center, Open-Label Study of VT3989, Alone or in Combination, in Patients With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 336
- 试验地点
- 12
- 主要终点
- Occurrence of Dose Limiting Toxicity
研究概览
简要总结
This is an open-label, dose escalation and expansion study to evaluate the safety, tolerability, PK, and biological activity of VT3989 administered, alone or in combination, once daily in patients with mesothelioma and/or metastatic solid tumors that are resistant to standard therapy or for which no effective standard therapy is available.
详细描述
Dose escalation (Part 1) will employ a traditional 3 + 3 design to assess safety of VT3989 in patients with metastatic solid tumors or mesothelioma. The 3 + 3 design will be implemented until the MTD or recommended phase 2 dose(s) and schedule(s) are determined. The MTD is defined as the highest dose level at which < 33% of patients experience a dose limiting toxicity (DLT) during the first cycle of the study (Cycle 1).
Dose Expansion (Part 2) will further evaluate the safety and assess preliminary antitumor activity at the recommended phase 2 dose(s) and schedule(s) with up to 6 cohorts. Expansion cohorts 1 and 2 will enroll patients with mesothelioma of any site origin with or without NF2 mutations. Expansion cohort 3 will enroll non-pleural mesothelioma patients. Expansion cohort 4 will enroll solid tumor patients with clearly inactivating NF2 mutations/alterations or YAP/TAZ gene rearrangements. Cohort 5 will enroll pleural mesothelioma patients.
Combination part (Part 3) includes two cohorts. Cohort A will enroll mesothelioma patients who will receive VT3989 in combination with immunotherapy (nivolumab plus ipilimumab). Cohort B will enroll NSCLC patients whose tumors have exon 19 deletion or exon 21 L858R mutation and will receive VT3989 in combination with targeted therapy (Osimertinib).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Part 3 Combination Cohort A: Patients with pathologically diagnosed, metastatic or unresectable malignant mesothelioma (including both pleural and non-pleural) who have not received systemic therapy.
- •Part 3 Combination Cohort B: Patients with pathologically diagnosed incurable locally advanced (inoperable or recurrent), or metastatic NSCLC with exon 19 deletions or exon 21 L858R mutations, with or without prior treatment with Osimertinib.
- •Measurable disease per RECIST v1.1 for non-pleural mesothelioma or other solid tumors or modified RECIST v1.1 for malignant pleural mesothelioma. mRECIST may be used for pleural extension of non-pleural mesothelioma or for mixed pleural and peritoneal (or other) mesothelioma.
- •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
- •Corrected QT (QTcF) interval > 470 msec (using Fridericia's correction formula); except for Part 2 Expansion Cohort 3, the QTcF interval criteria is > 450 msec).
- •Additional active malignancy that may confound the assessment of the study endpoints
- •Women who are pregnant or breastfeeding
- •Prior treatment with TEAD inhibitor, except for EHE patients.
研究组 & 干预措施
VT3989 Dose Escalation [Not Recruiting]
VT3989 dosed orally in 21 or 28 day cycles. Patients will be enrolled into escalating dose levels during the Dose Escalation Phase
干预措施: VT3989 (Drug)
Dose Expansion [Not Recruiting]
VT3989 dosed in 21 or 28 day cycles in patients with refractory metastatic solid tumors or mesothelioma.
干预措施: VT3989 (Drug)
Combination [Recruiting]
VT3989 dosed in 28 day cycles in patients with metastatic solid tumors or mesothelioma, in combination with immunotherapy (nivolumab/ipilimumab) or targeted therapy (osimertinib)
干预措施: VT3989 (Drug)
Combination [Recruiting]
VT3989 dosed in 28 day cycles in patients with metastatic solid tumors or mesothelioma, in combination with immunotherapy (nivolumab/ipilimumab) or targeted therapy (osimertinib)
干预措施: Nivolumab & Ipilimumab (Drug)
Combination [Recruiting]
VT3989 dosed in 28 day cycles in patients with metastatic solid tumors or mesothelioma, in combination with immunotherapy (nivolumab/ipilimumab) or targeted therapy (osimertinib)
干预措施: Osimertinib (Drug)
结局指标
主要结局
Occurrence of Dose Limiting Toxicity
时间窗: over the first 21 days of dosing
Incidence of Adverse and Serious Adverse Events
Occurrence of General Toxicity
时间窗: through study completion, an average of 30 months
Incidence of Adverse and Serious Adverse Events, Discontinuations due to Adverse Events and general safety evaluations
次要结局
- Tumor Response(through study completion, an average of 30 months)
- Pharmacokinetic Evaluation - Cmax(for first 6 cycles)
- Pharmacokinetic Evaluation - Tmax(for first 6 cycles)
- Pharmacokinetic Evaluation - Half-life(for first 6 cycles)
- Overall survival (Part 2, expansion cohort 3, 4, and 5)(Through study completion, an average of 30 months)
- Quality of life assessment (Part 2, expansion cohort 3, 4, and 5)(Through study completion, an average of 30 months)
- Progression free survival (Part 2, expansion cohort 3, 4, and 5)(Through study completion, an average of 30 months)