A Phase 1/2, Open-Label Dose Escalation and Expansion Study of SNV4818 as Monotherapy or in Combination With Other Anticancer Agents in Participants With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 320
- 试验地点
- 13
- 主要终点
- Incidence of dose limiting toxicities (DLTs)
研究概览
简要总结
This study is testing a new medicine, SNV4818, for people with advanced cancers. The researchers want to find out if SNV4818 is safe, well-tolerated, and effective in treating solid tumors. They are investigating different doses in order to find the safest and most effective one.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Advanced or metastatic solid tumor with an activating PIK3CA mutation.
- •Refractory to or intolerant of available therapies
- •Disease measurable by RECIST 1.1 criteria, or disease evaluable by clinically relevant tumor biomarkers in blood.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
排除标准
- •Diagnosis of a primary CNS malignancy
- •Active brain metastases or carcinomatous meningitis
- •Type 1 diabetes mellitus or uncontrolled type 2 diabetes mellitus
- •Inadequate organ function
- •Clinically significant ECG abnormalities, including QTcF ≥ 470 ms
研究组 & 干预措施
SNV4818 Monotherapy
Participants will receive oral, daily doses of SNV4818 as a single agent as part of either dose escalation or dose expansion cohorts. The SNV4818 dose level participants receive will depend upon the study part to which they are assigned. Dose escalation participants will be assigned to small cohorts of ascending SNV4818 dose levels. Dose expansion participants will receive one of the SNV4818 dose levels recommended for further evaluation.
干预措施: SNV4818 (Drug)
SNV4818+Fulvestrant Combination
Participants will receive oral, daily doses of SNV4818 in combination with a standard dose of Fulvestrant as part of either dose escalation or dose expansion cohorts.. The SNV4818 dose level participants receive will depend upon the study part to which they are assigned. Dose escalation participants will be assigned to small cohorts of ascending SNV4818 dose levels. Dose expansion participants will receive one of the SNV4818 dose levels recommended for further evaluation.
干预措施: SNV4818 (Drug)
SNV4818+Fulvestrant Combination
Participants will receive oral, daily doses of SNV4818 in combination with a standard dose of Fulvestrant as part of either dose escalation or dose expansion cohorts.. The SNV4818 dose level participants receive will depend upon the study part to which they are assigned. Dose escalation participants will be assigned to small cohorts of ascending SNV4818 dose levels. Dose expansion participants will receive one of the SNV4818 dose levels recommended for further evaluation.
干预措施: Fulvestrant (Drug)
SNV4818+Palbociclib+Fulvestrant Combination
Participants will receive oral, daily doses of SNV4818 in combination with a standard doses of Palbociclib and Fulvestrant as part of either dose escalation or dose expansion cohorts.. The SNV4818 dose level participants receive will depend upon the study part to which they are assigned. Dose escalation participants will be assigned to small cohorts of ascending SNV4818 dose levels. Dose expansion participants will receive one of the SNV4818 dose levels recommended for further evaluation.
干预措施: SNV4818 (Drug)
SNV4818+Palbociclib+Fulvestrant Combination
Participants will receive oral, daily doses of SNV4818 in combination with a standard doses of Palbociclib and Fulvestrant as part of either dose escalation or dose expansion cohorts.. The SNV4818 dose level participants receive will depend upon the study part to which they are assigned. Dose escalation participants will be assigned to small cohorts of ascending SNV4818 dose levels. Dose expansion participants will receive one of the SNV4818 dose levels recommended for further evaluation.
干预措施: Fulvestrant (Drug)
SNV4818+Palbociclib+Fulvestrant Combination
Participants will receive oral, daily doses of SNV4818 in combination with a standard doses of Palbociclib and Fulvestrant as part of either dose escalation or dose expansion cohorts.. The SNV4818 dose level participants receive will depend upon the study part to which they are assigned. Dose escalation participants will be assigned to small cohorts of ascending SNV4818 dose levels. Dose expansion participants will receive one of the SNV4818 dose levels recommended for further evaluation.
干预措施: Palbociclib (Drug)
结局指标
主要结局
Incidence of dose limiting toxicities (DLTs)
时间窗: First 28 days of study treatment
-Number of participants experiencing protocol-defined DLTs (Part 1A and 2A only)
Treatment Emergent Adverse Events (TEAEs)
时间窗: From first SNV4818 dose through approximately 30 days following the last SNV4818 dose
Incidence and frequency of TEAEs
次要结局
- Area Under Plasma Concentration (AUC) Time Curve of SNV4818(After 4 weeks (1 cycle) of study treatment)
- Maximum observed plasma concentration of SNV4818(After 4 weeks (1 cycle) of study treatment)
- Time to reach the maximum observed plasma concentration of SNV4818(After 4 weeks (1 cycle) of study treatment)
- Half-life of SNV4818(After 4 weeks (1 cycle) of study treatment)
- Area Under Plasma Concentration (AUC) Time Curve of SNV4818 extrapolated to infinity(After 1 day of study treatment)
- Apparent oral clearance of SNV4818(After 4 weeks (1 cycle) of study treatment)
- Apparent volume of distribution of SNV4818(After 4 weeks (1 cycle) of study treatment)
- Overall response rate (ORR)(After 8 weeks on study treatment)
- Disease control rate (DCR)(After 8 weeks on study treatment)
- Duration of response (DOR)(Up to approximately 2 years)