A Phase 1, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacodynamics and Preliminary Efficacy of Intratumoural Adze1.C in Participants With Metastatic Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 4
- 主要终点
- Incidence and severity of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
This is Phase I, open label, multi-center clinical trial evaluating an investigational treatment, Adze1.C. Adze1.C is a type of oncolytic virus therapy for adults with advanced Melanoma that have not responded to standard treatments. Oncolytic viruses are designed to infect and destroy cancer cells and have the potential to stimulate the immune system to fight tumors. The purpose of this study is to assess preliminary efficacy, determine the safety of Adze1.C, how well it is tolerated, and to identify the highest dose that can be safely given.
详细描述
This Phase 1, multicenter, open-label, dose-escalation study is designed to evaluate the safety, tolerability, pharmacodynamics, and preliminary efficacy of Adze1.C, a conditionally replicative oncolytic adenovirus encoding CD40L, in participants with metastatic melanoma.
Up to 30 participants will be enrolled across three sequential dose cohorts. All participants will first receive a low initial (seroconversion) dose of Adze1.C injected directly into their tumour. Three weeks later, they will receive a higher dose based on their assigned cohort:
cohort 1: Adze1.C 1 × 10E8 vp
cohort 2: Adze1.C 1 × 10E9 vp
cohort 3: Adze1.C 1 × 10E10 vp
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •Male or female participants aged 18 years or older at Screening.
- •Histologically confirmed unresectable Stage IIIB to IV metastatic melanoma.
- •Refractory to, or unsuitable for, standard treatment options as determined by the investigator.
- •Not a suitable candidate for curative resection.
- •Presence of measurable disease per iRECIST (excluding irradiated lesions unless progression post-radiation is documented).
- •Presence of at least one injectable melanoma lesion and/or tumor-involved lymph node suitable for intratumoral administration.
- •ECOG performance status of 0 or 1 at Screening.
- •Stable visceral metastases and stable CNS metastases may be eligible if protocol-defined eligibility requirements are met.
- •Willing and able to provide written informed consent and comply with study procedures.
排除标准
- •Uncontrolled intercurrent illness, including but not limited to:
- •Active systemic infection or fever ≥ 38°C within 5 days prior to Screening
- •Symptomatic congestive heart failure
- •NYHA Class III or IV heart failure
- •Unstable angina or arrhythmia
- •Leptomeningeal disease, active uncontrolled or symptomatic brain metastases, CNS haemorrhage, uncontrolled peri-tumoural oedema, or conditions associated with high risk of CNS inflammation
- •Psychiatric illness or social conditions that limit compliance
- •Visceral metastatic disease that is not clinically and radiographically stable or requires urgent medical intervention.
- •Immunocompromised status or known HIV infection with ongoing antiretroviral therapy.
- •Active or clinically significant liver disease, including:
- •Hepatitis B surface antigen (HBsAg) positive
- •Hepatitis C virus RNA positive
- •History of organ transplantation.
- •Prior treatment with adenovirus therapy.
- •Prior oncolytic virus treatment within 2 months of Screening.
- •Use of systemic immunosuppressants or other immune-modifying drugs must be discontinued 14 days prior to the first dose.
- •Use of cidofovir within 14 days of Adze1.C dosing.
- •Any other condition which, in the investigator's judgment, would make the participant inappropriate for the study.
研究组 & 干预措施
Adze1.C Dose Escalation
Participants will receive Adze1.C by intratumoural injection. All will begin with a low seroconversion dose (1 million viral particles (vp)), followed three weeks later by an escalation dose based on cohort assignment:
Cohort 1: 100 million vp Cohort 2: 1 billion vp Cohort 3: 10 billion vp
Doses are given every two weeks for up to 14 weeks. Dose escalation follows a 3+3 design to evaluate safety, tolerability, and early signs of efficacy.
干预措施: Adze1.C (Drug)
结局指标
主要结局
Incidence and severity of treatment-emergent adverse events (TEAEs)
时间窗: From Day 1 (first dose) through Week 16 (end of treatment visit)
Safety will be assessed based on the frequency, nature, and severity of TEAEs, graded per CTCAE v5.0.
Incidence of dose-limiting toxicities (DLTs)
时间窗: Week 1 Day 1 to Week 6 Day 1 (5-week DLT evaluation period)
Number of participants who experience DLTs during the 5-week period following the seroconversion and escalation doses, per predefined DLT criteria.
Incidence and severity of treatment-emergent adverse events (TEAEs)
时间窗: From Day 1 (first dose) through Week 16 (end of treatment visit)
Safety will be assessed based on the frequency, nature, and severity of TEAEs, graded per CTCAE v5.0.
Incidence of dose-limiting toxicities (DLTs)
时间窗: Week 1 Day 1 to Week 6 Day 1 (5-week DLT evaluation period)
Number of participants who experience DLTs during the 5-week period following the seroconversion and escalation doses, per predefined DLT criteria.
次要结局
- Recommended Phase 2 Dose (RP2D) determination(Through Week 16)
- Detection of viral shedding in bodily fluids(From Day 1 through Week 16)
- Objective response rate (ORR)(From first dose through disease progression (estimated up to 6 months))
- Progression-Free Survival (PFS)(From first dose to disease progression or death (estimated up to 12 months))
- Patient-reported quality of life using EORTC QLQ-C30(From baseline to Week 16)
- Objective response rate (ORR)(From first dose through disease progression (estimated up to 6 months))
- Progression-Free Survival (PFS)(From first dose to disease progression or death (estimated up to 12 months))
- Patient-reported quality of life using EORTC QLQ-C30(From baseline to Week 16)
- Recommended Phase 2 Dose (RP2D) determination(Through Week 16)
- Detection of viral shedding in bodily fluids(From Day 1 through Week 16)