A Phase 1, Open-Label, 2-Part, Multicenter, First-in-Human Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-Tumor Activity of the STAT3 Inhibitor VVD-130850 as Single Agent and in Combination With Checkpoint Inhibition in Participants With Advanced Solid and Hematologic Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 132
- 试验地点
- 29
- 主要终点
- Dose Escalation: Incidence and Severity of Dose-limiting Toxicities (DLTs) During DLT Observation Period
研究概览
简要总结
A FIH study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of VVD-130850, as single agent and in combination with checkpoint inhibition, in participants with advanced solid and hematologic tumors.
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
- •Histologically or cytologically confirmed metastatic or unresectable solid tumor or advanced non-Hodgkin's lymphoma (NHL).
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Adequate organ and bone marrow function as defined in the protocol.
- •For Combination Therapy Expansion:
- •Serine/threonine kinase 11/ liver kinase B1 (STK11/LKB1) mutated non-small cell lung cancer (NSCLC) as assessed by historical (local) test.
- •Must be refractory to or have progressed on or after a platinum-based doublet regimen and an immune checkpoint inhibitor (CPI). These therapies could have been given in the same line of therapy or different lines of therapy.
- •Measurable disease by RECIST version 1.1 as assessed by the Investigator.
排除标准
- •Have a diagnosis of immunodeficiency or are receiving systematic steroid therapy or any other form of immunosuppressive therapy.
- •Prior allogeneic transplantation.
- •History of cardiac diseases as defined in detail in the protocol.
- •Clinically significant infection or any eye infection.
- •Active central nervous system (CNS) malignancies (previously treated CNS malignancies are not exclusionary).
- •Combination Therapy Expansion:
- •Known hypersensitivity or contraindication to pembrolizumab or any of its components.
- •Any prior toxicity (Grade 3 or 4) related to immunotherapy leading to treatment discontinuation with the exception of the history of immunotherapy-related endocrinopathy controlled with ongoing medical management (e.g., hypothyroidism, adrenal insufficiency, diabetes).
研究组 & 干预措施
Dose Escalation: VVD-130850 Single Agent
Participants will receive ascending doses of VVD-130850, orally, once daily in 21-day treatment cycles during the dose escalation phase.
干预措施: VVD-130850 (Drug)
Dose Escalation: VVD-130850 + Pembrolizumab Combination Therapy
Participants will receive ascending doses of VVD-130850, orally, once daily, along with pembrolizumab intravenous (IV) infusion, every 3 weeks (Q3W) in 21-day treatment cycles during the dose escalation phase.
干预措施: VVD-130850 (Drug)
Dose Escalation: VVD-130850 + Pembrolizumab Combination Therapy
Participants will receive ascending doses of VVD-130850, orally, once daily, along with pembrolizumab intravenous (IV) infusion, every 3 weeks (Q3W) in 21-day treatment cycles during the dose escalation phase.
干预措施: Pembrolizumab (Drug)
Dose Expansion: VVD-130850 Single Agent
Participants will receive VVD-130850 at recommended dose for expansion (RDE), orally, once daily in 21-day treatment cycles during the dose expansion phase.
干预措施: VVD-130850 (Drug)
Dose Expansion: VVD-130850 + Pembrolizumab Combination Therapy
Participants will receive VVD-130850 at RDE orally, once daily along with pembrolizumab IV infusion, Q3W in 21-day treatment cycles during the dose expansion phase.
干预措施: VVD-130850 (Drug)
Dose Expansion: VVD-130850 + Pembrolizumab Combination Therapy
Participants will receive VVD-130850 at RDE orally, once daily along with pembrolizumab IV infusion, Q3W in 21-day treatment cycles during the dose expansion phase.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Dose Escalation: Incidence and Severity of Dose-limiting Toxicities (DLTs) During DLT Observation Period
时间窗: From Day 1 to Day 21 of Cycle 1 [cycle length=21 days]
Incidence and severity of DLTs will be assessed per DLT criteria set forth in the protocol based on adverse events (AEs) evaluated per National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Dose Expansion: Number of Participants with Clinically Significant Changes in Laboratory Evaluations
时间窗: Up to approximately 4 years
Dose Expansion: Number of Participants with Clinically Significant Changes in Vital Signs
时间窗: Up to approximately 4 years
Dose Expansion: Number of Participants with AEs and Serious Adverse Events (SAEs)
时间窗: Up to approximately 4 years
次要结局
- Dose Escalation: QT/Corrected QT (QTc) Interval and Other Electrocardiogram (ECG) Parameters(Up to approximately 4 years)
- Dose Expansion: Overall Response Rate (ORR)(Up to approximately 4 years)
- Dose Expansion: Disease Control Rate (DCR)(Up to approximately 4 years)
- Dose Escalation: Recommended Dose for Expansion (RDE) of VVD-130850 as a Single Agent and in Combination with Pembrolizumab(Up to approximately 4 years)
- Dose Escalation and Expansion: Area Under the Plasma Concentration-time Curve (AUC) of VVD-130850(Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days))
- Dose Escalation and Expansion: Maximum Plasma Concentration (Cmax) of VVD-130850(Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days))
- Dose Escalation and Expansion: Apparent Terminal Half-life (t1/2) of VVD-130850(Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days))
- Dose Expansion: Progression-free Survival (PFS)(Up to approximately 4 years)
- Dose Expansion: Duration of Response (DoR)(Up to approximately 4 years)