A Phase 1/1b, Open-Label, Multicenter, First-in-Human Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Anti-Tumor Activity of VVD-159642, a RAS-PI3Kα Inhibitor, as a Single Agent and in Combination in Participants With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 220
- 试验地点
- 9
- 主要终点
- Part 1: Incidence and Severity of Dose-limiting Toxicities (DLTs)
研究概览
简要总结
A FIH study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of VVD-159642, a rat sarcoma viral oncogene-phosphatidylinositol 3-kinase alpha (RAS-PI3Kα) inhibitor, as a single agent and in combination with either sotorasib or trametinib in participants with advanced solid 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
- •For Part 1 Dose Escalation, the prospective participant must have histologically confirmed pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), non-small cell lung cancer (NSCLC), or any solid tumor that harbors a rat sarcoma viral oncogene (RAS) alteration [Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), Harvey rat sarcoma viral oncogene homolog (HRAS)] as per local /historical testing; any solid tumor that harbors an epidermal growth factor receptor (EGFR) alteration as per local/historical testing; or human epidermal growth factor receptor 2 (HER2) overexpression (immunohistochemistry [IHC] 3+ or IHC 2+/fluorescence in situ hybridization [FISH] positive) as per local/historical testing.
- •Have histologically or cytologically confirmed metastatic or unresectable solid tumors.
- •Measurable disease by RECIST version 1.1 as assessed by the investigator.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Adequate bone marrow, kidney, and liver function as defined in the protocol.
- •Able to take oral medications.
排除标准
- •Active central nervous system (CNS) malignancies.
- •History of cardiac diseases as defined in detail in the protocol.
- •Uncontrolled arterial hypertension despite optimal medical management (per investigator's opinion).
- •History of inflammatory bowel disease or any malabsorption syndrome or any conditions that would interfere with enteral absorption and/or may interfere with the conduct of the study.
- •Active hepatitis B infection [positive for hepatitis B surface antigen and Hepatitis B virus deoxyribonucleic acid (DNA)].
- •Active hepatitis C infection (positive anti-hepatitis C virus [HCV] antibody and quantitative HCV ribonucleic acid (RNA) results greater than the lower limits of detection of the assay).
研究组 & 干预措施
Part 1: Dose Escalation: VVD-159642 Single Agent
Participants will receive ascending doses of VVD-159642, orally, daily in 21-day treatment cycles during Part 1.
干预措施: VVD-159642 (Drug)
Part 2: Dose Expansion (Cohort A): VVD-159642 Single Agent
Participants will receive VVD-159642 at the recommended dose for expansion (RDE), orally, daily in 21-day treatment cycles during Part 2.
干预措施: VVD-159642 (Drug)
Part 2: Dose Expansion (Cohort B): VVD-159642 + Sotorasib
Participants will receive VVD-159642 at RDE orally, daily in combination with sotorasib, in 21-day treatment cycles after a safety run-in.
干预措施: VVD-159642 (Drug)
Part 2: Dose Expansion (Cohort B): VVD-159642 + Sotorasib
Participants will receive VVD-159642 at RDE orally, daily in combination with sotorasib, in 21-day treatment cycles after a safety run-in.
干预措施: Sotorasib (Drug)
Part 2: Dose Expansion (Cohort C): VVD-159642 + Trametinib
Participants will receive VVD-159642 at RDE orally, daily in combination with trametinib, in 21-day treatment cycles after a safety run-in.
干预措施: VVD-159642 (Drug)
Part 2: Dose Expansion (Cohort C): VVD-159642 + Trametinib
Participants will receive VVD-159642 at RDE orally, daily in combination with trametinib, in 21-day treatment cycles after a safety run-in.
干预措施: Trametinib (Drug)
结局指标
主要结局
Part 1: Incidence and Severity of Dose-limiting Toxicities (DLTs)
时间窗: From Day 1 to Day 21 of Cycle 1 [cycle length=21 days]
Part 2: Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to approximately 29 months
Part 2: Incidence and Severity of Clinically Significant Changes in Vital Signs
时间窗: Up to approximately 29 months
Part 2: Incidence and Severity of Clinically Significant Changes in Laboratory Evaluations
时间窗: Up to approximately 29 months
次要结局
- Part 1: Recommended Dose for Expansion (RDE) of VVD-159642 as a Single Agent(Up to approximately 29 months)
- Part 2: Recommended Phase 2 Dose (RP2D) of VVD-159642 as a Single Agent and in Combination with Sotorasib and Trametinib(Up to approximately 29 months)
- Part 2: Overall Response Rate (ORR)(Up to approximately 29 months)
- Part 2: Duration of Response (DoR)(Up to approximately 29 months)
- Part 2: Progression-free Survival (PFS)(Up to approximately 29 months)
- Part 2: Disease Control Rate (DCR)(Up to approximately 29 months)
- Parts 1 and 2: Area Under the Plasma Concentration-time Curve (AUC) of VVD-159642 as a Single Agent and in Combination With Sotorasib and Trametinib(Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days))
- Parts 1 and 2: Maximum Plasma Concentration (Cmax) of VVD-159642 as a Single Agent and in Combination With Sotorasib and Trametinib(Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days))
- Parts 1 and 2: Half-life (t1/2) of VVD-159642 as a Single Agent and in Combination With Sotorasib and Trametinib(Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days))