A Study of the Safety and Efficacy of IMM-101 in Combination With Checkpoint Inhibitor Therapy in Patients With Advanced Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Safety and Tolerability of the Combination of IMM-101 + Nivolumab
研究概览
简要总结
The purpose of this study is to assess the safety and efficacy of the combination of IMM-101 with nivolumab.
详细描述
This open-label study will assess the safety and efficacy of the combination of IMM-101 with nivolumab in patients with unresectable stage III, or stage IV melanoma who are either treatment-naive (cohort A) or whose disease has progressed during PD-1 blockade (cohort B). Ipilimumab may be used as a subsequent treatment in place of nivolumab alongside IMM-101 for patients in cohort B if their disease progresses on study. Eighteen patients will be enrolled into cohort A and 8 patients into cohort B.
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-confirmed diagnosis of advanced (unresectable Stage III) or metastatic (Stage IV) melanoma.
- •At least one measurable lesion by CT or MRI, according to RECIST 1.
- •Eastern Cooperative Oncology Group (ECOG)/World Health Organisation (WHO) Performance Status of ≤1 at Day
- •Known BRAF V600 mutation status or consent to BRAF V600 mutation testing during the Screening Period.
- •Prior radiotherapy must have been completed at least 2 weeks prior to study drug administration (Week 0, Visit 1). Prior adjuvant or neoadjuvant melanoma therapy is permitted if it was completed at least 6 weeks prior to enrolment (Week 0, Visit 1), and all related adverse events have resolved or stabilised.
- •Patient is considered suitable for treatment with nivolumab.
- •For cohort A, the following key inclusion criteria apply:
- •Patient is treatment-naive (i.e. no prior systemic anticancer therapy for unresectable or metastatic melanoma).
- •For cohort B, the following key inclusion criteria apply:
- •Patient is either currently receiving treatment with an anti-PD-1 therapy (monotherapy or in combination with ipilimumab), for advanced melanoma and has progressive disease by RECIST 1.1 after 4 or more doses; or has previously received at least 4 doses of PD-1 targeted therapy, alone or in combination with ipilimumab, had disease progression by RECIST 1.1 during this therapy and has not received any further therapy for advanced melanoma.
排除标准
- •Uveal/ocular melanoma.
- •Active brain metastases or leptomeningeal metastases. Patients with brain metastases are eligible for cohort B of the study only, if these have been treated and there is no MRI evidence of progression for at least 8 weeks after treatment is complete and within 21 days prior to first dose of study treatment administration.
- •Patient has documented history of clinically severe autoimmune disease or a syndrome that requires systemic steroids or immunosuppressive agents.
- •Patient has a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or immunosuppressant drugs (such as azathioprine, tacrolimus, cyclosporin) within the 14 days period before the first administration of IMM-
- •For cohort A, patients meeting the following key criteria are also ineligible to participate in this study:
- •Patient has received prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-PD ligand-1 (PD-L1), anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) agent.
- •For cohort B, patients meeting the following key criteria are also ineligible to participate in this study:
- •Patient has received more than one treatment regimen for advanced (stage III/IV) disease prior to their anti PD-1 therapy.
研究组 & 干预措施
IMM-101 (and nivolumab or ipilimumab)
Patients in cohort A were given IMM-101 in combination with nivolumab. Patients in cohort B who fail to respond to treatment with IMM-101 and nivolumab, and who meet certain criteria, have the option to change treatment on study to IMM-101 and ipilimumab.
干预措施: Nivolumab (Drug)
IMM-101 (and nivolumab or ipilimumab)
Patients in cohort A were given IMM-101 in combination with nivolumab. Patients in cohort B who fail to respond to treatment with IMM-101 and nivolumab, and who meet certain criteria, have the option to change treatment on study to IMM-101 and ipilimumab.
干预措施: Ipilimumab (Drug)
IMM-101 (and nivolumab or ipilimumab)
Patients in cohort A were given IMM-101 in combination with nivolumab. Patients in cohort B who fail to respond to treatment with IMM-101 and nivolumab, and who meet certain criteria, have the option to change treatment on study to IMM-101 and ipilimumab.
干预措施: IMM-101 (Drug)
结局指标
主要结局
Safety and Tolerability of the Combination of IMM-101 + Nivolumab
时间窗: From the point of Informed Consent until end of the study assessment (up to 84 weeks) or until withdrawal from the study.
Incidence, frequency and severity of treatment emergent adverse events (TEAEs) throughout the study.
Overall Response Rate
时间窗: From enrollment to end of study (18 months) or withdrawal, whichever was soonest
The primary endpoint of Overall Response Rate (ORR) is defined as the number of subjects with a Best Overall Response (BOR) of confirmed Complete Response (CR) or Partial Response (PR) divided by the number of subjects in the Intent-to-treat analysis set in each cohort of the study. The BOR will be determined once all the data up to and including the 12-month assessments for Cohort A or the 6-month assessment for Cohort B are available. It is defined as the best response designation based on confirmed responses determined by the investigator according to RECIST 1.1, recorded between the date of first postscreening scan and the date of last scan at/prior to the assessment at the 12-month assessment (Cohort A) and 6-month assessment/last assessment prior to change of treatment to IMM-101 + ipilimumab whichever is sooner (Cohort B).
次要结局
- Best Overall Response (BOR) Using RECIST 1.1(18 months)
- Progression Free Survival (PFS)(From Visit 1 (week 0) and the first confirmation of progression using RECIST 1.1 (confirmed or unconfirmed), or death from any cause (whichever occurred first).)
- Overall Survival (OS)(Overall survival was defined as the time from Visit 1 (week 0) until the end of the study (80 weeks) or until the date of death from any cause.)
- Overall Survival (OS) at One Year(OS at 1 year was calculated after all patients had had the opportunity of 12 months treatment of study)