A Phase I, Open-Label, Multicenter, Dose Escalation and Cohort Expansion Study of SPYK04 as Monotherapy in Patients With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 85
- 试验地点
- 22
- 主要终点
- Safety and tolerability of SPYK04 (Dose limiting toxicities) [Dose escalation]
研究概览
简要总结
Phase I, open-label, multi-center study
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
- •(Both Part I and Part II)
- •Age >= 18 years at time of signing informed consent form
- •ECOG performance status of 0 or 1
- •Patients with a locally advanced, recurrent, or metastatic solid tumor for which standard therapy either does not exist or has proven ineffective or intolerable
- •(Part I only)
- •Patients with measurable and/or evaluable disease per RECIST v1.1
- •Patients with MAPK pathway alterations positive solid tumor (i.e., BRAF, K/N/H-RAS mutations)
- •(Part II only)
- •Patients with measurable disease per RECIST v1.1
- •Patients with KRAS mutated NSCLC (NSCLC cohort)
- •Patients with KRAS mutated Ovarian Cancer (Ovarian Cancer cohort)
- •Patients with RAS mutated solid tumor (Biopsy cohort)
排除标准
- •(Both Part I and Part II)
- •Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), unstable angina, or myocardial infarction within the previous 6 months or unstable arrhythmias within the previous 3 months
- •Patients with primary central nervous system (CNS) malignancy, untreated CNS metastases requiring any anti-tumor treatment, or active CNS metastases
- •Patients with current severe, uncontrolled systemic disease (including, but not limited to, clinically significant cardiovascular disease, pulmonary disease, or renal disease, ongoing or active infection)
- •Patients with a history or complication of interstitial lung disease (ILD)
研究组 & 干预措施
Expansion part in NSCLC, ovarian cancer and other solid tumors
Patients will receive SPYK04 at the recommended dose.
干预措施: SPYK04 (Drug)
Dose escalation cohort of SPYK04
Patients will receive SPYK04 at escalated dose.
干预措施: SPYK04 (Drug)
结局指标
主要结局
Safety and tolerability of SPYK04 (Dose limiting toxicities) [Dose escalation]
时间窗: From first dose until the end of Cycle 1 (approximately 35 days)
Incidence and nature of DLTs
Preliminary anti-tumor activity of SPYK04 [Cohort expansion]
时间窗: From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to 42 months (study completion)
Objective Response Rate (ORR) is defined as proportion of patients who had a confirmed complete response (CR) or partial response (PR), as determined by the investigator with use of Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
Safety and tolerability of SPYK04 (Adverse Events) [Dose escalation]
时间窗: From Cycle 0 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion)
Incidence, nature, and severity of adverse events (AEs) as assessed by the NCI CTCAE v5.0
Pharmacokinetics of SPYK04 [Dose escalation]
时间窗: From Cycle 0 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion)
Plasma concentrations of SPYK04
Safety and tolerability of SPYK04 (Electrocardiograms in triplicate) [Dose escalation]
时间窗: From first dose until the end of Cycle 1 (approximately 35 days)
Uncorrected QT interval, QTcF, PR duration, QRS interval and RR interval
次要结局
- Safety and tolerability of SPYK04 (AEs) [Cohort expansion](From Cycle 1 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion))
- Preliminary anti-tumor activity of SPYK04 [Dose escalation](From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to 42 months (study completion))
- Preliminary anti-tumor activity of SPYK04 [Cohort expansion](From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to 42 months (study completion))
- Pharmacodynamics of SPYK04 [Cohort expansion](From screening until the time of partial response or stable disease lasting for more than 4 months, and the time of progressive disease, if possible, an average of 1 year)
- Pharmacokinetics of SPYK04 [Cohort expansion](From Cycle 1 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion))