A Phase Ib/II Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of HMPL-453 Tartrate as Monotherapy and in Combination With Chemotherapy or Toripalimab in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 190
- 试验地点
- 2
- 主要终点
- Safety and tolerability(Incidence and severity of adverse events (AEs))
研究概览
简要总结
A Phase Ib/II Clinical Study Evaluating HMPL-453 Tartrate as Monotherapy and in Combination with Chemotherapy or Toripalimab in Advanced Solid Tumors
详细描述
The study includes a dose escalation phase and a dose-expansion phase.
Patients with advanced solid tumor will be enrolled in the dose escalation phase to assess the tolerability, safety, and PK profile of HMPL-453 monotherapy or combination therapy.
Patients with specific types of advanced or metastatic tumors harboring certain FGFR gene alterations will be enrolled in the dose expansion phase to assess the preliminary efficacy of HMPL-453 monotherapy or combination therapy.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Dose escalation phase: patients with histologically or cytologically confirmed locally advanced or metastatic solid tumor who progressed on or are intolerant of standard therapy;
- •Dose expansion phase: patients with UC, GC/GEJ, or IHCC harboring specific FGFR gene alterations;
- •Age 18 to 75 years;
- •Those who are able to give written informed consent, and able to comply with protocol-specified visits and related procedures;
- •Ability to swallow study drug;
- •ECOG PS of 0 or 1;
- •Measurable lesion according to RECIST v1.1, refer to the protocol;
- •Adequate organ and bone marrow function;
- •Life expectancy ≥ 12 weeks;
- •Female patients or male patients with partners of childbearing potential must take effective contraceptive measures per the protocol.
排除标准
- •Patients who previously received selective FGFR targeting therapy;
- •Concurrent participation in another interventional clinical study, excluding those in the follow-up period and have not recently received investigational intervention;
- •Current or previous history of central nervous system (CNS) metastases；
- •Current or previous history of retinal detachment；
- •Known history of primary immunodeficiency;
- •Female patients who are pregnant or lactating；
- •Patients who in the opinion of the investigator may be unsuitable for participating in the study;
- •Patients with acute or chronic active hepatitis B or C infection;
- •Known human immunodeficiency virus (HIV) infection and syphilis infection；
- •Clinically significant cardiovascular disease such as congestive heart failure or arrhythmia；
- •Uncontrolled hypertension despite optimal medical management；
- •Received live vaccine within 30 days before the first dose of study drug(s);
- •Those who have undergone major surgical procedures (craniotomy, thoracotomy or laparotomy) within 4 weeks prior to the first study treatment or who are expected to be in need of major surgery; those with unhealed wounds, ulcers or fractures.
研究组 & 干预措施
dose escalation phase of HMPL-453 monotherapy or combination therapy
HMPL-453 monotherapy or combination therapy
干预措施: HMPL-453 (Drug)
dose escalation phase of HMPL-453 monotherapy or combination therapy
HMPL-453 monotherapy or combination therapy
干预措施: gemcitabine and cisplatin (Drug)
dose escalation phase of HMPL-453 monotherapy or combination therapy
HMPL-453 monotherapy or combination therapy
干预措施: toripalimab (Drug)
结局指标
主要结局
Safety and tolerability(Incidence and severity of adverse events (AEs))
时间窗: 6 months after the last patient enrolled
DLT, TEAEs and SAEs
Preliminary efficacy/Objective response rate (ORR)
时间窗: up to 2 years
Objective response rate (ORR) in patients with the selected tumors along with certain FGFR gene alterations
次要结局
- Efficacy/Progression-free survival (PFS)(up to 2 years)
- time to response (TTR)(up to 2 years)
- disease control rate (DCR)(up to 2 years)
- overall survival (OS)(up to 2 years)
- duration of response (DoR）(up to 2 years)