A Phase Ib, Open-label Study of Oral BGJ398 in Combination With Oral BYL719 in Adult Patients With Select Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 62
- 试验地点
- 8
- 主要终点
- Incidence rate of dose limiting toxicities (DLTs) of the combination of BGJ398 with BYL719
研究概览
简要总结
To study the safety and efficacy of the combination of BGJ398 with BYL719 in patients whose tumors express mutations to PIK3CA with or without alterations to FGFR 1-3.
详细描述
This dose escalation/dose expansion study will evaluate the combination of orally administered BGJ398 in combination with orally administered BYL719. During the dose escalation part, the MTD of the combination will be determined in patients whose advanced or metastatic tumors express mutations to PIK3CA. Once the MTD has been determined, the expansion part will begin. Patients will be addd to one of three arms based on the disease type and genetic changes. Patients with metastatic colorectal cancer are not eligible for participation in the expansion part.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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/cytologically confirmed advanced or metastatic solid tumors who have failed standard therapy or for whom no effective standard anti-cancer therapy exists
- •Documented PIK3CA mutations in all patients in dose escalation and expansion with or without documented genetic alterations in FGFR depending upon dose expansion cohort (either local or central determination)
- •Measurable disease defined by RECIST v1.1
- •ECOG performance status of ≤2
排除标准
- •Prior PI3Ki or selective FGFR inhibitor treatment (for patients enrolled to expansion part)
- •Colorectal cancer (for patients enrolled to expansion part)
- •Patients with diabetes mellitus requiring insulin treatment and/or with clinical signs or with fasting glucose ≥ 140 mg/dL / 7.8 mmol/L, history of clinically significant gestational diabetes mellitus or documented steroid-induced diabetes mellitus
- •Use of medications that increase serum levels of phosphorus and/or calcium
- •Inorganic phosphorus outside of normal limits
- •Total and ionized serum calcium outside of normal limits
研究组 & 干预措施
Metastatic breast cancer
Evaluation of safety and efficacy in patients with metastatic breast cancer whose tumors contain mutations to PIK3CA and alterations FGFR 1-3.
干预措施: BGJ398 (Drug)
Metastatic breast cancer
Evaluation of safety and efficacy in patients with metastatic breast cancer whose tumors contain mutations to PIK3CA and alterations FGFR 1-3.
干预措施: BYL719 (Drug)
Solid tumor arm 1
Patients with solid tumors (except for colorectal cancer) whose tumors express mutations to PIK3CA.
干预措施: BGJ398 (Drug)
Solid tumor arm 1
Patients with solid tumors (except for colorectal cancer) whose tumors express mutations to PIK3CA.
干预措施: BYL719 (Drug)
Solid tumor arm 2
Patients with solid tumors (except for colorectal cancer) whose tumomrs express mutations to PIK3CA and alterations to FGFR 1-3
干预措施: BGJ398 (Drug)
Solid tumor arm 2
Patients with solid tumors (except for colorectal cancer) whose tumomrs express mutations to PIK3CA and alterations to FGFR 1-3
干预措施: BYL719 (Drug)
Dose escalation
To determine the MTD or RDE of the combination of BGJ398 with BYL719 in patients with advanced or metastastic solid tumors that express mutations to PIK3CA.
干预措施: BGJ398 (Drug)
Dose escalation
To determine the MTD or RDE of the combination of BGJ398 with BYL719 in patients with advanced or metastastic solid tumors that express mutations to PIK3CA.
干预措施: BYL719 (Drug)
结局指标
主要结局
Incidence rate of dose limiting toxicities (DLTs) of the combination of BGJ398 with BYL719
时间窗: Approximately 8 months
The dose escalation part of the study will be guided by a well-established statistical method/model to estimate the maximum tolerated dose(s) and/or the recommended dose for expansion (RDE). Safety(incidence and nature of DLTs), pharmacokinetic and pharmacodynamic data will guide dose escalation decisioins.
次要结局
- Progression free survival(Every two months from the date of baseline CT scan)
- Overall response rate(Every two months from the date of baseline CT scan)
- Time vs. concentration profile of BGJ398 and BYL719(Every 28 days for up to 10 cycles)
- Safety and tolerability of BGJ398/BYL719 combination at the recommended dose for expansion (RDE)(Every 28 days from baseline visit until end of study visit)