An Open-label Phase 1/2 Study to Evaluate the Safety, Biological Response and Efficacy of a Single Dose of Temferon (Autologous CD34+-Enriched Hematopoietic Stem and Progenitors Cells Genetically Modified With Human Interferon-α2) in Patients With Metastatic Renal Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Tolerability and safety of conditioning and Temferon, over the first 90 days following administration, as determined by the incidence of adverse events
研究概览
简要总结
This is an open label, single-centre phase 1/2 study involving a single dose of Temferon, an investigational Advanced Therapy Medicinal Product (ATMP), to treat patients with metastatic clear cell renal cell carcinoma (RCC) with evidence of disease progression following at least two lines of standard of care (SoC) treatments.
详细描述
During Part A (Phase 1) of the study, Temferon will be administered to up to 12 patients, who are going to be split into two cohorts according to immune checkpoint inhibitor -ICI- therapy received in the six months prior to entry into the study, with a histologically confirmed diagnosis of metastatic RCC and evidence of disease progression following at least two lines of SoC treatments.
At D+30 after Temferon, patients will start to receive pembrolizumab providing they have not received ICI in the 6 months prior to entry into the study. Patients allocated to pembrolizumab will receive pembrolizumab 400mg IV every 6 weeks commencing at D+30.
In the event that a patient has received ICI in the 6 months prior to study entry, they will be allocated to the cabozantinib arm. Patients allocated to cabozantinib, will initiate treatment with 40mg QD once PD occurs as assessed at D+30 or at subsequent visits.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient aged between 18 - 70 years old
- •Women of childbearing potential must have a negative pregnancy test at screening and agree to use two distinct acceptable methods of contraception (which may include partner contraception) for the duration of the study
- •Men with partners of childbearing potential must be willing to use acceptable barrier contraceptive method during the trial or have undergone a vasectomy at least 6 months prior to study entry and confirmed by semen analysis
- •Adequate cardiac, renal, hepatic, pulmonary, and hematologic function
- •Patient able and willing to provide written informed consent and comply with study protocol and procedures
- •Histologically confirmed diagnosis of unresectable, locally advanced/metastatic RCC with clear cell component, with or without sarcomatoid features
- •Presence of a disease burden sufficiently large to permit biopsy
- •Disease progression following approved standard of care treatments for metastatic disease
- •ECOG PS 0-1
- •Measurable disease at physical examination or at imaging assessment according to RECIST 1.1 criteria
排除标准
- •Use of investigational agents or procedures in the 4 weeks prior to study enrolment (6 weeks for long-acting agents) or receipt of an experimental gene therapy product in the past 2 years
- •History of current evidence of neuropsychiatric illness
- •History of severe cardiovascular disease
- •Evidence of haematological neoplasm
- •Active alcohol or substance abuse within 6 months of the study
- •Current pregnancy or lactation
- •Expected to undergo a surgical intervention during the first 3 months of the study
- •Known bleeding diathesis or history of abnormal/severe bleeding or any other known coagulation abnormalities that would contraindication a tissue biopsy, active treatment with anticoagulants.
- •New CNS or rapidly growing metastases or carcinomatous meningitis
- •Presence of hepatic metastases
- •Previous allogenic bone marrow, renal, liver transplant
- •Prior use of immunosuppressives in the previous 4 weeks prior to enrolment
- •Clinically relevant active viral, bacterial or fungal infection
- •Active autoimmune disease requiring disease modifying treatment.
研究组 & 干预措施
Pembrolizumab cohort
At D+30 after Temferon, patients will start to receive pembrolizumab providing they have not received ICI in the 6 months prior to entry into the study. Patients allocated to pembrolizumab will receive pembrolizumab 400mg IV every 6 weeks commencing at D+30.
干预措施: Temferon (Genetic)
Pembrolizumab cohort
At D+30 after Temferon, patients will start to receive pembrolizumab providing they have not received ICI in the 6 months prior to entry into the study. Patients allocated to pembrolizumab will receive pembrolizumab 400mg IV every 6 weeks commencing at D+30.
干预措施: Pembrolizumab (Biological)
Cabozantinib cohort
At D+30 after Temferon, in the event that a patient has received ICI in the 6 months prior to study entry and in case PD occurs (as assessed at D+30 or at subsequent visits), they will be receiving cabozantinib. Patients allocated to cabozantinib cohort will initiate treatment with 40mg QD
干预措施: Temferon (Genetic)
Cabozantinib cohort
At D+30 after Temferon, in the event that a patient has received ICI in the 6 months prior to study entry and in case PD occurs (as assessed at D+30 or at subsequent visits), they will be receiving cabozantinib. Patients allocated to cabozantinib cohort will initiate treatment with 40mg QD
干预措施: Cabozantinib (Drug)
结局指标
主要结局
Tolerability and safety of conditioning and Temferon, over the first 90 days following administration, as determined by the incidence of adverse events
时间窗: First 90 days
To assess tolerability and safety of conditioning and Temferon over the first 90 days following Temferon administration, as evaluated by the incidence of \>=CTCAE Grade 2 adverse events.
Biological activity of Temferon, over the first 90 days following administration, as determined by the presence of Temferon-derived progeny in the tumor (IFN gene signature)
时间窗: First 90 days
To assess the biological activity of Temferon in the tumor of patients with metastatic renal cell carcinoma, over the first 90 days following Temferon administration, as determined by the change in IFN (interferon) gene signature in the tumor
次要结局
- Proportion of patients achieving hematological recovery by Day +30(Day 30)
- Disease control rate following Temferon infusion(Through study completion, an average of 1 year)
- Long term tolerability and safety of Temferon as determined by the incidence of adverse events up to 1 year following Temferon administration according to CTCAE v5.0 criteria(1 year following Temferon administration)
- Incidence, severity and duration of adverse events of special interest as indicated on the study protocol(Through study completion, an average of 1 year)
- Overall response rate per RECIST version 1.1(RECIST criteria used at Screening, Baseline, Day +72, Day +120, Day +180, Day +210, Day +270, Day +360 or at any time disease progression or a secondary malignancy is suspected)