A Phase 1b/2 Study of an Immunotherapeutic Vaccine, DPX-Survivac With Low Dose Cyclophosphamide and Epacadostat (INCB024360) in Patients With Recurrent Ovarian Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 85
- 试验地点
- 9
- 主要终点
- Safety as measured by adverse event reporting (CTCAE)
研究概览
简要总结
T cell activating therapy DPX-Survivac, low dose oral cyclophosphamide, and IDO1 inhibitor epacadostat will be tested together for the first time in patients with recurrent ovarian, fallopian tube, or peritoneal cancer to determine the safety and potential immune-modulating activity of the combination of these agents.
详细描述
The Phase 1b component is a multicenter, non-randomized, open label, uncontrolled, safety and effectiveness study to identify the recommended Phase 2 dose (R2PD) of epacadostat in combination with DPX-Survivac and cyclophosphamide.
The Phase 2 component was initially a multicenter, randomized, open-label study to evaluate the safety and effectiveness of DPX-Survivac + cyclophosphamide with or without the RP2D of epacadostat. The design of the study has been amended to a single arm study in which up to 16 evaluable subjects will be enrolled to received DPX-Survivac plus intermittent low dose cyclophosphamide (i.e. treatment arm 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
- Female
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed, stage IIc-IV epithelial ovarian, fallopian tube or peritoneal cancer
- •Platinum-resistant or -sensitive subjects after completing first-line treatment (debulking surgery and adjuvant or neoadjuvant treatment with standard of care treatment such as carboplatin and paclitaxel). Subjects may have had any number of subsequent lines of chemotherapy.
- •Must have evidence of progressive disease with either biochemical (i.e. rising CA-125) and/or radiologic progression
- •Must have measurable disease by RECIST v1.1, a successful pre-treatment tumor biopsy, and be willing to undergo tumor biopsy during treatment
- •Ambulatory with an ECOG 0-1
- •Life expectancy ≥ 6 months
- •Meet protocol-specified laboratory requirements
排除标准
- •Eligible for otherwise curative treatment or undergoing concurrent therapy
- •Prior receipt of survivin based vaccines or immune checkpoint inhibitors (e.g. anti-CTLA-4, anti-PD-1, anti-PD-L1, or any other antibody or drug specifically targeting T cell co-stimulation) or an IDO inhibitor
- •Concurrent second malignancy other than non-melanoma skin cancer, cervical carcinoma in situ, or controlled bladder cancer
- •Clinical ascites
- •Any single lesion greater than or equal to 4 cm (per RECIST v1.1)
- •Malignant bowel obstruction
- •History of autoimmune disease requiring treatment within the last two years (except vitiligo or diabetes)
- •Recent history of thyroiditis
- •Presence of a serious acute infection or chronic infection
- •Active central nervous system (CNS) or leptomeningeal metastasis (brain metastases)
- •GI condition that might limit absorption of oral agents
- •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 monoamine oxidase inhibitors (MAOIs) or UGT1A9 inhibitors
- •Receipt of live attenuated vaccines
- •Acute or chronic skin and/or microvascular disorders
- •Edema or lymphedema in the lower limbs > grade 2
研究组 & 干预措施
Arm 1
DPX-Survivac, Cyclophosphamide, Epacadostat (Phase 1 and initially Phase 2)
干预措施: DPX-Survivac (Other)
Arm 1
DPX-Survivac, Cyclophosphamide, Epacadostat (Phase 1 and initially Phase 2)
干预措施: Cyclophosphamide (Drug)
Arm 1
DPX-Survivac, Cyclophosphamide, Epacadostat (Phase 1 and initially Phase 2)
干预措施: Epacadostat (INCB024360) (Drug)
Arm 2
DPX-Survivac, Cyclophosphamide (in Phase 2 only)
干预措施: DPX-Survivac (Other)
Arm 2
DPX-Survivac, Cyclophosphamide (in Phase 2 only)
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Safety as measured by adverse event reporting (CTCAE)
时间窗: up to 13 months
Objective Response Rate (Phase 2 only)
时间窗: up to 13 months
Evaluated using modified RECIST v1.1
次要结局
- Objective Response Rate (for each treatment group)(up to 13 months)
- Duration of Response(up to 13 months)
- Cell mediated immunity as measured by the antigen specific response in peripheral blood(bimonthly for up to 13 months)
- Evaluation of treatment-induced changes in tumor infiltrating lymphocytes(at 8 to 10 weeks)
- Time to Progression(up to 13 months)
- Overall Survival(up to 13 months)