A Phase 2, Open-label, Multicenter, Study of an Immunotherapeutic Treatment, DPX-Survivac in Combination With Low Dose Cyclophosphamide and Pembrolizumab, in Subjects With Selected Advanced and Recurrent Solid Tumours.
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 184
- 试验地点
- 23
- 主要终点
- Efficacy as measured by objective response rate
研究概览
简要总结
This study will assess the safety and efficacy of DPX-Survivac and low dose cyclophosphamide with pembrolizumab in subjects with selected advanced and recurrent solid tumours.
详细描述
This study is a Phase 2 with safety lead-in study to assess the safety and efficacy of DPX-Survivac, low dose cyclophosphamide, and pembrolizumab combination therapy in subjects with selected advanced and recurrent solid tumours. Two ovarian cancer arms will be recruited and randomized in this study, one with and one without cyclophosphamide. All other cohorts will be single arm, receiving treatment with the triple combination.
Up to 20 subjects, from any cohort, will be enrolled to assess the safety of study treatments before the study moves to the expansion phase. Once the safety lead-in is completed, the five cohorts will be expanded to recruit additional subjects following a Simon two stage design. Enrollment in the ovarian cancer cohort will be randomized 1:1 into two arms.
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
- •Subjects with advanced or metastatic solid tumours who have completed treatment with first line therapy:
- •Epithelial ovarian, fallopian tube, or peritoneal cancer
- •Hepatocellular carcinoma
- •Non-small cell lung cancer
- •Urothelial cancer
- •Microsatellite instability high solid tumours, other than the above indications
- •Radiologic and/or biochemical evidence of disease progression
- •Completion of pre-treatment tumour biopsy
- •Must have measurable disease by RECIST v1.1
- •Ambulatory with an ECOG 0-1
- •Life expectancy ≥ 6 months
- •Meet protocol-specified laboratory requirements
排除标准
- •Chemotherapy or immunotherapy within treatment within 28 days of start of study treatment
- •Radiotherapy within treatment within 2 weeks of start of study treatment
- •Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor where subject was discontinued from that treatment due to a Grade 3 or higher immune-related toxicity
- •For NSCLC subjects: Known EGFR mutations or ALK rearrangements
- •Prior receipt of survivin-based vaccine(s) and/or immunotherapies
- •Concurrent second malignancy other than non-melanoma skin cancer, cervical carcinoma in situ, or controlled bladder cancer
- •Clinical ascites or pleural fluid that cannot be managed
- •Malignant bowel obstruction or recent history of bowel obstruction
- •For OvCa, subjects with any single lesion greater than 5 cm
- •Autoimmune disease requiring treatment within the last two years (except replacement therapy)
- •Recent history of thyroiditis
- •Any history of (non-infectious) pneumonitis that required steroid therapy or current pneumonitis
- •Presence of a serious acute or chronic infection
- •Active CNS metastases and/or carcinomatous meningitis
- •GI condition that might limit absorption of oral agents
- •Allogenic tissue/solid organ transplant
- •Other serious intercurrent chronic or acute illness, including myocardial infarction or cerebrovascular event within 6 months
- •Ongoing treatment with steroid therapy or other immunosuppressive
- •Receipt of live attenuated vaccines
- •Acute or chronic skin and/or microvascular disorders
- •Edema or lymphedema in the lower limbs > grade 2
- •Severe hypersensitivity (≥ Grade 3) to pembrolizumab
研究组 & 干预措施
Arm 1 (All cohorts)
DPX-Survivac, Cyclophosphamide, Pembrolizumab
干预措施: DPX-Survivac (Other)
Arm 1 (All cohorts)
DPX-Survivac, Cyclophosphamide, Pembrolizumab
干预措施: Cyclophosphamide (Drug)
Arm 1 (All cohorts)
DPX-Survivac, Cyclophosphamide, Pembrolizumab
干预措施: Pembrolizumab (Drug)
Arm 2 (Ovarian cohort only)
DPX-Survivac, Pembrolizumab
干预措施: DPX-Survivac (Other)
Arm 2 (Ovarian cohort only)
DPX-Survivac, Pembrolizumab
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Efficacy as measured by objective response rate
时间窗: Approximately 24 months
Centrally evaluated using RECIST v1.1
Safety as measured by the rate of adverse events
时间窗: Approximately 24 months
Using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0
次要结局
- Progression Free Survival(Approximately 24 months)
- Disease control rate(Approximately 24 months)
- Objective response rate(Approximately 24 months)
- Duration of response(Approximately 24 months)
- Overall survival(Approximately 24 months)