A Phase 1b/2 Trial Evaluating the Safety, Tolerability, and Preliminary Efficacy of Melphalan Percutaneous Hepatic Perfusion Therapy (HEPZATO KIT™) With Nivolumab and Relatlimab (Opdualag) in Patients With Metastatic Melanoma and Liver Metastasis
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Incidence and Severity of Dose Limiting Toxicities (DLTs)
研究概览
简要总结
This study is being done to see if combining HEPZATO KIT™ with nivolumab and relatlimab (Opdualag™) in patients with metastatic melanoma with liver metastasis is safe, tolerable, and will have a synergistic effect leading to improved clinical outcomes compared to the historic cohort of patients with liver metastasis treated with combination immune checkpoint inhibitor therapy.
详细描述
Co-Primary Objectives
- To evaluate the safety and tolerability of HEPZATO KIT™ in combination with nivolumab and relatlimab (Opdualag™) in subjects with metastatic melanoma and liver metastasis (LM).
- To evaluate the preliminary systemic efficacy of HEPZATO KIT™ in combination with nivolumab and relatlimab (Opdualag™), as measured by objective response rate (ORR), in subjects with metastatic melanoma and LM.
Secondary Objectives
- To evaluate the preliminary systemic efficacy of HEPZATO KIT™ in combination with nivolumab and relatlimab (Opdualag™), as measured by ORR, in both hepatic and non-hepatic target lesions in subjects with metastatic melanoma and LM.
- To evaluate the disease control rate (DCR) in subjects with metastatic melanoma and LM receiving HEPZATO KIT™ in combination with nivolumab and relatlimab (Opdualag™).
- To evaluate the PFS in subjects with metastatic melanoma and LM receiving HEPZATO KIT™ in combination with nivolumab and relatlimab (Opdualag™).
- To evaluate the overall survival (OS) in subjects with metastatic melanoma and LM receiving HEPZATO KIT™ in combination with nivolumab and relatlimab (Opdualag™).
- To evaluate the duration of response (DOR) in subjects with metastatic melanoma and LM receiving HEPZATO KIT™ in combination with nivolumab and relatlimab (Opdualag™).
- To evaluate the tumor reduction at any time during treatment in subjects with metastatic melanoma and LM receiving HEPZATO KIT™ in combination with nivolumab and relatlimab (Opdualag™).
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
- •Histologically or cytologically confirmed metastatic melanoma with liver metastasis (LM). Liver biopsy positive for presence of melanoma metastases is required.
- •0-1 line of prior systemic therapy in the unresectable/metastatic setting - prior adjuvant anti-programmed cell death-1 (anti-PD-1) or BRAF/MEK targeted therapy is considered 1 line of prior systemic therapy if less than 6 months from the last treatment.
- •Evaluable/measurable disease according to RECIST v1.
- •Demonstrate adequate organ function; all screening labs to be obtained within 28 days prior to registration.
- •Patients must weigh greater than or equal to 35 kilograms (due to possible size limitations with respect to percutaneous catheterization of the femoral artery and vein using the Delcath Hepatic Delivery System).
排除标准
- •Prior treatment with HEPZATO KIT™ or nivolumab and relatlimab (Opdualag™)
- •Radiotherapy is permitted within 30 days prior to C1D1 as long as radiation is given with palliative intent and towards a non-target lesion.
- •History of hypersensitivity or treatment discontinuation due to grade 3+ immune-related adverse events (irAEs) from prior anti-PD-(L)1 therapy. Patients who are able to successfully resume immune checkpoint therapy without recurrence of grade 3 irAEs are eligible to participate.
- •Symptomatic or uncontrolled brain metastases, leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation.
- •Prednisone use greater than or equal to 10 mg/d or equivalent
- •Organ transplant recipients
研究组 & 干预措施
Participants with Metastatic Melanoma
干预措施: Nivolumab and Relatlimab (Drug)
Participants with Metastatic Melanoma
干预措施: Melphalan (Device)
结局指标
主要结局
Incidence and Severity of Dose Limiting Toxicities (DLTs)
时间窗: up to 12 weeks
A DLT is defined as any grade 4+ non-hematologic event lasting greater than 3 days (despite appropriate medical management) considered possibly related to study treatment (HEPZATO KIT™ or Opdualag™) within 12 weeks of Cycle 1 Day 1.
Incidence of Treatment-Emergent Adverse Events
时间窗: up to 2 years
Incidence of Serious Treatment-Emergent Adverse Events
时间窗: up to 2 years
Number of Participants that Discontinue Treatment due to Adverse Events
时间窗: up to 2 years
Overall Response Rate (ORR)
时间窗: After treatment plus follow up for 2 years (up to 4 years)
The objective response rate is the proportion of all participants with confirmed Partial Response (PR) or Complete Response (CR) according to RECIST 1.1, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment).
次要结局
- ORR in Hepatic and Non-Hepatic Lesions(After treatment plus follow up for 2 years (up to 4 years))
- Disease Control Rate (DCR)(After treatment plus follow up for 2 years (up to 4 years))
- Progression Free Survival (PFS)(After treatment plus follow up for 2 years (up to 4 years))
- Overall Survival (OS)(After treatment plus follow up for 2 years (up to 4 years))
- Duration of Response (DOR)(After treatment plus follow up for 2 years (up to 4 years))
- Number of Participants with Tumor Reduction at any time(After treatment plus follow up for 2 years (up to 4 years))