A Phase 1/1b Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of APS03118 in Adult Patients With Unresectable Locally Advanced or Metastatic Solid Tumors Harboring RET Mutations or Fusions
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 108
- 试验地点
- 1
- 主要终点
- The maximum tolerated dose (MTD) and / or recommended Phase II dose (RP2D)
研究概览
简要总结
This is a Phase 1/1b, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary antineoplastic activity of APS03118 administered orally in participants with RET-altered solid tumors.
详细描述
After being informed about the study procedure and potential risks and benefits, all patients giving written informed consent will undergo a 4-week screening period to determine eligibility for study entry. The eligible participants will be enrolled using a rolling 6 dose escalation scheme to identify MTD and/or RP2D.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Male or female patients aged 18 years or older
- •Have histological or cytological confirmation of unresectable locally advanced or metastatic solid tumors harboring oncogenic RET mutations or fusions confirmed by NGS. Site may identify patients with a RET-mutated or RET-fusion solid tumor before the formal screening.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or
- •Resolution of all toxic effects of prior therapies to Grade 1 or below according to NCI CTCAE version 5.0 (except alopecia or Grade 2 neuropathy);
- •Patients with asymptomatic brain metastases if they have been previously treated, demonstrated no progression at least for 1 months before Screening, are asymptomatic and have had no requirement for steroids or enzyme inducing anticonvulsants in the last 14 days before Screening
- •Adequate organ function
排除标准
- •Have a locally advanced solid tumor that is a candidate for curative surgery treatment through radical surgery and/or radiotherapy.
- •Have an active fungal, bacterial, and/or active untreated viral infection
- •The patient has a serious pre-existing medical condition(s)
- •Have received or will receive a COVID-19 vaccine within 1 month before the first dose of APS03118.
研究组 & 干预措施
APS03118 Dose Escalation
APS03118 administered orally
干预措施: APS03118 (Drug)
结局指标
主要结局
The maximum tolerated dose (MTD) and / or recommended Phase II dose (RP2D)
时间窗: Approximately 15 months
The MTD is defined as the maximum dose at which the incidence of dose-limiting toxicities (DLTs) during Cycle 1 is below 30%(\<2/6)
Incidence of DLTs during Cycle 1 in dose-escalation cohorts
时间窗: Within the 28 days of the first APS03118 dose for each patient
次要结局
- Adverse events(AE)(Approximately 24 months)
- Disease Control Rate (DCR)(Up to approximately 24 months)
- Peak Plasma Concentration (Cmax)(Up to approximately 1 month)
- Area under the plasma concentration versus time curve (AUC)(Up to approximately 1 month)
- Progress Free Survival (PFS)(Up to approximately 24 months)
- Time to Maximum Concentration (Tmax)(Up to approximately 1 month)
- Degree of accumulation(Up to approximately 1 month)
- Overall Response Rate (ORR)(Up to approximately 24 months)
- Duration of response (DOR)(Up to approximately 24 months)
- Best of response (BOR)(Up to approximately 24 months)