Phase 1/2 Dose-Escalation and Expansion Study of FLX475 Alone and in Combination With Pembrolizumab in Advanced Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 323
- 试验地点
- 67
- 主要终点
- Safety and tolerability of FLX475 as a single agent and in combination with pembrolizumab measured by the incidence of adverse events, including dose-limiting toxicities and maximum tolerated dose
研究概览
简要总结
This clinical trial is a Phase 1/2, open-label, sequential-group, dose-escalation and cohort expansion study to determine the safety and preliminary anti-tumor activity of FLX475 as monotherapy and in combination with pembrolizumab.
The study will be conducted in 2 parts, a dose-escalation phase (Part 1) and a cohort expansion phase (Part 2). In Part 1 of the study, subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 as monotherapy or in combination with pembrolizumab. In Part 2 of the study, subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 as monotherapy or in combination with pembrolizumab.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented advanced or metastatic cancer ineligible for standard therapies with one of the following histologies
- •Dose Escalation: non-small cell lung cancer, head and neck squamous cell carcinoma, nasopharyngeal carcinoma, metastatic triple negative breast cancer, urothelial carcinoma, gastric cancer, esophageal carcinoma, cervical cancer, classical Hodgkin lymphoma
- •Dose Expansion: nasopharyngeal carcinoma, lymphoma, head and neck squamous cell carcinoma, cervical cancer, non-small cell lung cancer, triple-negative breast cancer
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
- •Evaluable disease at baseline (at least one measurable target lesion by imaging for expansion cohorts)
- •Tumor available for biopsy
排除标准
- •History of allergy or severe hypersensitivity to biologic agents
- •History of Grade 3-4 immune-related adverse events leading to discontinuation of prior immuno-oncology treatment
- •Active autoimmune disease or serious autoimmune disease within past 2 years requiring systemic therapy
- •History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, (non-infectious) pneumonitis that required steroids, or symptoms of active pneumonitis
- •Prior allogeneic hematopoietic stem cell transplant within 5 years, or prior allogeneic organ transplant
- •Active graft-versus-host disease
研究组 & 干预措施
Part 2b: Combination Expansion Cohorts
Eligible subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 in combination with pembrolizumab; additional subjects in each cohort may be enrolled in Stage 2.
干预措施: pembrolizumab (KEYTRUDA®) (Drug)
Part 1b: Combination Dose Escalation
Eligible subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 in combination with pembrolizumab.
干预措施: pembrolizumab (KEYTRUDA®) (Drug)
Part 1a: Monotherapy Dose Escalation
Eligible subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 as monotherapy.
干预措施: FLX475 (tivumecirnon) (Drug)
Part 1b: Combination Dose Escalation
Eligible subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 in combination with pembrolizumab.
干预措施: FLX475 (tivumecirnon) (Drug)
Part 2a: Monotherapy Expansion Cohorts
Eligible subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 as monotherapy; additional subjects in each cohort may be enrolled in Stage 2.
干预措施: FLX475 (tivumecirnon) (Drug)
Part 2b: Combination Expansion Cohorts
Eligible subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 in combination with pembrolizumab; additional subjects in each cohort may be enrolled in Stage 2.
干预措施: FLX475 (tivumecirnon) (Drug)
结局指标
主要结局
Safety and tolerability of FLX475 as a single agent and in combination with pembrolizumab measured by the incidence of adverse events, including dose-limiting toxicities and maximum tolerated dose
时间窗: Approximately 18 weeks
Overall response rate in subjects treated with FLX475 as a single agent and in combination with pembrolizumab
时间窗: Through study completion (approximately 2 years)
Overall Response Rate in Subjects Treated With FLX475 as a Single Agent and in Combination With Pembrolizumab
时间窗: Through study completion (approximately 2 years)
Summary of Best Overall Response
Safety and Tolerability of FLX475 as a Single Agent and in Combination With Pembrolizumab Measured by the Incidence of Adverse Events, Including Dose-limiting Toxicities and Maximum Tolerated Dose
时间窗: Approximately 18 weeks
treatment-emergent adverse events
次要结局
未报告次要终点