A Phase 1 Safety Pilot/Phase II, Open-label Study of Varlilumab (CDX-1127) in Combination With Ipilimumab and CDX-1401 in Patients With Unresectable Stage III or Stage IV Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 8
- 主要终点
- Phase l: Safety and tolerability of varlilumab in combination with ipilimumab as measured by incidences of drug related adverse events (AEs), serious drug related AEs, dose-limiting toxicities and laboratory test abnormalities.
研究概览
简要总结
This is a study to determine the clinical benefit (how well the drug works), safety and tolerability of combining a) varlilumab and ipilimumab and b) varlilumab, ipilimumab, CDX-1401 and poly-ICLC. The study will enroll patients with unresectable Stage III or Stage IV melanoma.
详细描述
Varlilumab is a fully human monoclonal antibody that binds to a molecule called CD27 found on certain immune cells and may act to promote anti-tumor effects.
Yervoy™ (Ipilimumab) is a human monoclonal antibody that blocks CTLA-4, a protein receptor that downregulates the immune system.
CDX-1401 is a vaccine made of a fully human monoclonal antibody linked to NY-ESO-1 and is designed to deliver NY-ESO-1 to professional antigen presenting cells for generating robust immune responses against cancer cells expressing NY-ESO-1. CDX-1401 is administered with poly-ICLC, an adjuvant that enhances vaccine-induced immune responses.
This study will evaluate the safety, tolerability and efficacy of varlilumab and ipilimumab, with or without the addition of CDX-1401/poly-ICLC, in patients with melanoma.
Eligible patients that enroll in the Phase I portion of the study will be assigned to one of two possible dose levels of varlilumab in combination with 3 mg/kg ipilimumab. The first phase of the study will test the safety profile of the combination and determine which dose of varlilumab will be studied in Phase II of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Histologic diagnosis of melanoma.
- •Unresectable Stage III or IV disease
- •Documented progressive disease based on radiographic, clinical or pathologic assessment.
- •No more than three prior anticancer regimens (BRAF/MEK inhibitors, IL-2 or investigational agents) including no more than one chemotherapy-containing regimen for advanced (recurrent, locally advanced or metastic) disease.
- •Measurable disease.
- •Life expectancy ≥ 12 weeks.
- •If of childbearing potential (male or female), agrees to practice an effective form of contraception during study treatment and for at least 70 days following last treatment.
- •Availability of tumor tissue for central laboratory analyses.
排除标准
- •Previous treatment with anti-CD27 antibody, ipilimumab or other anti-CTLA-4 targeted therapies. Previous therapy with other checkpoint blockers such as anti-PD-1 or anti-PD-L1 is acceptable, unless treatment was discontinued for intolerance.
- •For patients enrolled to Phase II Cohort B: Previous administration of vaccine therapy targeting NY-ESO-
- •BRAF/MEK inhibitors within 2 weeks prior to first dose of study treatment.
- •Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to first dose of study treatment.
- •Monoclonal based therapies within 4 weeks and all other immunotherapy within 2 weeks prior to first dose of study treatment.
- •Systemic radiation therapy within 4 weeks, focal radiotherapy within 2 weeks and radiopharmaceuticals (strontium, samarium) within 8 weeks prior to first dose of study treatment.
- •Ocular Melanoma
- •Other prior malignancy, except for adequately treated basal or squamous cell skin cancer or in situ cancers; or any other cancer from which the patient has been disease-free for at least 3 years.
- •Active, untreated central nervous system metastases.
- •Active autoimmune disease or documented history of autoimmune disease.
- •Active diverticulitis
- •Significant cardiovascular disease including CHF or poorly controlled hypertension.
研究组 & 干预措施
Phase l: varlilumab and ipilimumab
干预措施: Combination of varlilumab and ipilimumab (Drug)
结局指标
主要结局
Phase l: Safety and tolerability of varlilumab in combination with ipilimumab as measured by incidences of drug related adverse events (AEs), serious drug related AEs, dose-limiting toxicities and laboratory test abnormalities.
时间窗: Safety follow-up is 70 days from last study drug dose.
Phase ll: The objective response rate (ORR) is defined as the proportion of patients who achieve radiographic partial or complete response (PR or CR) according to the mWHO tumor response criteria.
时间窗: Up to 24 weeks
次要结局
未报告次要终点