A Phase 1a/1b Open-label, Dose-Escalation and Expansion Study of ACTM-838 as a Single Agent in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 5
- 主要终点
- Incidence and severity of adverse events and serious adverse events - Part 1a
研究概览
简要总结
This is a first in human (FIH) 2-part study using ACTM-838 in patients with advanced solid tumors resistant to standard of care treatment. Part 1a will evaluate dose escalation and Part 1b will evaluate dose expansion.
详细描述
This study has 2 parts. Part 1a will evaluate the safety and tolerability and activity of escalating doses of ACTM-838 to estimate the maximum tolerated dose (MTD) and/or the optimum biological dose (OBD) for ACTM-838 as a monotherapy and determine the dose recommended for Part 1b.
Part 1b will further evaluate ACTM-838 in patients with advanced specific tumor types (defined pathologically, clinically and/or molecularly) based on data emerging from the Phase 1a and the pre-clinical program. The details on the Phase 1b dose expansion part will be incorporated in a future protocol amendment.
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
盲法说明
Open label
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
- •Advanced solid tumor for which there is no remaining standard curative therapy and no therapy with a demonstrated survival benefit, or they must be ineligible to receive or refuse to receive such therapy
- •At least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST ) v1.1; amenable for biopsy, and radiographically apparent on computed tomography (CT) or magnetic resonance imaging (MRI )
- •Eastern Cooperative Oncology Group (ECOG) 0-1
- •Adequate hematologic, hepatic, pulmonary, and cardiac function
- •CD4 count >500/mL at screening
- •Additional protocol defined inclusion criteria may apply
排除标准
- •Active autoimmune disease requiring systemic treatment (i.e., with use of disease modifying agents, systemic corticosteroids or immunosuppressive drug) within the past 6 months prior to dosing of investigational product.
- •History of permanent artificial implants (e.g., prosthetic joints, artificial heart valves, pacemakers, orthopaedic screw[s], metal plate[s], bone graft[s], or other exogenous implant[s]
- •Known history of cholelithiasis or urolithiasis
- •History of valvular disease, arterial aneurisms or arterial or venous malformation
- •Known active brain metastases
- •Documented active Salmonella infection or vaccination with Salmonella typhi within 6 months prior to investigational product dosing
- •Additional protocol defined inclusion/exclusion criteria may apply
研究组 & 干预措施
ACTM-838 Monotherapy
Escalating doses of ACTM-838 in Part 1a followed by expansion in Part 1b at the recommended dose determined in Part 1a
干预措施: ACTM-838 (Drug)
结局指标
主要结局
Incidence and severity of adverse events and serious adverse events - Part 1a
时间窗: 1 year
Proportion of participants experiencing dose limiting toxicities - Part 1a
时间窗: 28 Days
次要结局
- Objective response rate (ORR) defined as complete response (CR) or partial response (PR) - Part 1a(1 year)
- Confirmed ORR defined as confirmed CR or confirmed PR - Part 1a(1 year)
- Clinical Benefit Rate (CR, PR, or stable disease (SD) as best overall response) - Part 1a(1 year)
- Duration of Response (DoR), defined as the time from date of first response (CR or PR) - Part 1a(1 year)
- Progression free survival (PFS) - Part 1a(1 year)
- Change in tumor markers - Part 1a(1 year)
- Amount of ACTM-838 in blood, urine, and faeces as measured by digital droplet-polymerase chain reaction (ddPCR) - Part 1a(1 year)
- Tumor PD colonization as measured by ddPCR and payload delivery as measured by RNA detection - Part 1a(1 year)
- Incidence of antidrug antibodies (ADA) to ACTM-838 - Part 1a(1 year)