Open-Label Multicenter Phase 1b/2 Study of Nanatinostat + Valganciclovir in Patients With Advanced Epstein-Barr Virus-Positive Solid Tumors and in Combination With Pembrolizumab in Patients With Recurrent/Metastatic Nasopharyngeal Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 26
- 试验地点
- 13
- 主要终点
- Phase 1b: Incidence of Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
This study will evaluate the safety and efficacy of nanatinostat in combination with valganciclovir in patients with relapsed/refractory EBV-positive solid tumors and in combination with pembrolizumab in patients with recurrent/metastatic nasopharyngeal carcinoma
详细描述
This is an open-label, multicenter Phase 1b/2 study evaluating nanatinostat in combination with valganciclovir alone and in combination with pembrolizumab. Nanatinostat is a selective class I HDAC inhibitor which induces EBV early lytic phase protein generation, activating (val)ganciclovir to its cytotoxic form.
The Phase 1b dose escalation portion is designed to evaluate safety and to determine the recommended Phase 2 dose (RP2D) in patients with EBV+ RM-NPC followed by a Project Optimus | FDA (https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus) cohort to confirm the RP2D. Up to 60 patients with EBV+ RM-NPC will be randomized 1:1 to receive nanatinostat in combination with valganciclovir at the confirmed RP2D with or without pembrolizumab to evaluate safety, overall response rate, and potential pharmacodynamic markers in the Phase 2 dose expansion part of the study. Additionally, patients with other EBV+ solid tumors will be enrolled to receive nanatinostat in combination with valganciclovir at the RP2D in a Phase 1b cohort.
The study was prematurely terminated after the end of Phase 1b and did not proceed to Phase 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Recurrent or metastatic EBV+ nasopharyngeal carcinoma (RM-NPC) for whom no potentially curative options are available, who have received at least 1 prior line of platinum-based chemotherapy and no more than 3 prior lines of therapy for RM-NPC.
- •Phase 1b exploratory proof-of-concept cohort only: Advanced/metastatic EBV+ non-NPC solid tumors with no available curative therapies.
- •Measurable disease per RECIST v1.1
- •ECOG performance status 0 or 1
- •Adequate bone marrow and liver function
排除标准
- •Anti-tumor treatment with cytotoxic drugs, biologic therapy, immunotherapy, or other investigational drugs within 4 weeks or >5 half-lives, whichever is shorter
- •Active CNS disease
- •Inability to take oral medication, malabsorption syndrome or any other gastrointestinal condition (nausea, diarrhea, vomiting) that may impact the absorption of nanatinostat and valganciclovir
- •Active infection requiring systemic therapy
- •Active autoimmune disease that has required systemic therapy with modifying agents, corticosteroids, or immunosuppressive agents
- •Positive hepatitis B or hepatitis C
研究组 & 干预措施
Nanatinostat in combination with valganciclovir
Phase 1b: Nanatinostat dose escalation starting at 20 mg orally daily, 4 days per week, and valganciclovir starting at 900 mg orally daily, then Phase 2: Nanatinostat and valganciclovir at the confirmed recommended Phase 2 dose
干预措施: Nanatinostat (Drug)
Nanatinostat in combination with valganciclovir
Phase 1b: Nanatinostat dose escalation starting at 20 mg orally daily, 4 days per week, and valganciclovir starting at 900 mg orally daily, then Phase 2: Nanatinostat and valganciclovir at the confirmed recommended Phase 2 dose
干预措施: Valganciclovir (Drug)
Nanatinostat in combination with valganciclovir and pembrolizumab
Phase 2: Nanatinostat and valganciclovir at the confirmed recommended Phase 2 doses in combination with pembrolizumab 200 mg intravenous (IV) every 3 weeks
干预措施: Nanatinostat (Drug)
Nanatinostat in combination with valganciclovir and pembrolizumab
Phase 2: Nanatinostat and valganciclovir at the confirmed recommended Phase 2 doses in combination with pembrolizumab 200 mg intravenous (IV) every 3 weeks
干预措施: Valganciclovir (Drug)
Nanatinostat in combination with valganciclovir and pembrolizumab
Phase 2: Nanatinostat and valganciclovir at the confirmed recommended Phase 2 doses in combination with pembrolizumab 200 mg intravenous (IV) every 3 weeks
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Phase 1b: Incidence of Dose-Limiting Toxicities (DLTs)
时间窗: DLT period of 28 days
Percentage of patients experiencing a DLT, defined as an adverse event or clinically significant abnormal laboratory value that is at least possibly related to study drugs and is not primarily related to disease, disease progression, concomitant medication(s), or intercurrent illness
Phase 2: Overall Response Rate (ORR)
时间窗: Approximately 3 years
Percentage of patients with a complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 (v1.1)
次要结局
- Incidence of Adverse Events(Approximately 3 years)
- Phase 2: Duration of Response (DOR)(Approximately 3 years)
- Phase 2: Disease Control Rate (DCR)(Approximately 3 years)
- Phase 2: Progression-Free Survival (PFS)(Approximately 3 years)
- Phase 2: Overall Survival (OS)(Approximately 3 years)
- Pharmacokinetic Parameter (Nanatinostat) - Time to Maximum Plasma Concentration [Tmax](Approximately 28 days following enrollment)
- Pharmacokinetic Parameter (Ganciclovir) - Time to Maximum Plasma Concentration [Tmax](Approximately 28 days following enrollment)
- Pharmacokinetic Parameter (Nanatinostat) - Maximum Plasma Concentration [Cmax](Approximately 28 days following enrollment)
- Pharmacokinetic Parameter (Ganciclovir) - Maximum Plasma Concentration [Cmax](Approximately 28 days following enrollment)
- Pharmacokinetic Parameter (Nanatinostat) - Area Under the Plasma Concentration-Time Curve [AUC0-t](Approximately 28 days following enrollment)
- Pharmacokinetic Parameter (Ganciclovir) - Area Under the Plasma Concentration-Time Curve [AUC0-t](Approximately 28 days following enrollment)
- Pharmacokinetic Parameter (Nanatinostat) - Half-Life of Nanatinostat [t1/2](Approximately 28 days following enrollment)
- Pharmacokinetic Parameter (Ganciclovir) - Half-Life of Ganciclovir [t1/2](Approximately 28 days following enrollment)