A First-in-Human (FIH), Open-Label, Phase 1/2 Dose Escalation and Expansion Study of ADG126, ADG126 in Combination With Anti PD1 Antibody, and ADG126 in Combination With ADG106 in Patients With Advanced/Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Adagene Inc
- 入组人数
- 58
- 试验地点
- 9
- 主要终点
- Number of participants with adverse events as assessed by CTCAE v5.0 ADG126-ADG106 combination regimens
研究概览
简要总结
ADG126, ADG126 in Combination with anti-PD1 antibody, and ADG126 in Combination with ADG106 in Patients with Advanced/Metastatic Solid Tumors .
详细描述
ADG126 is a novel anti-CTLA-4 fully human IgG1 antibody prodrug that is modified with Adagene Safebody technology to control the activation of anti-CTLA4 activity.ADG106 is a fully human ligand-blocking, agonistic anti-CD137 IgG4 mAb which is expected to enhance the activity of activated T cells. The enhanced antitumor efficacy results observed from the preclinical studies of ADG126 in combination with ADG106 or anti-PD-1 provided further support to explore such combinations in clinical settings for better patient responses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Adults ≥18 years of age.
- •ECOG performance status 0 or
- •Estimated life expectancy of more than 12 weeks .
- •Patients with advanced or metastatic solid tumors, confirmed by histologically or pathologically documented, who have progressed after all standard therapies, or for whom no further standard therapy exists.
- •At least 1 measurable lesion at baseline according to the definition of RECIST v1.
- •Adequate organ function.
- •Meets the additional tumor type requirements as specified in Protocol.
排除标准
- •Treatment with any investigational drug within washout period.
- •Major trauma or major surgery within 4 weeks prior to first dose of study drug(s)
- •History of significant immune-mediated AE.
- •Central nervous system (CNS) disease involvement.
- •Prior organ allograft transplantations or allogeneic peripheral blood stem cell (PBSC)/bone marrow (BM) transplantation
- •Clinically significant cardiac disease.
- •Evidence of active uncontrolled viral, bacterial, or systemic fungal infection.
- •Patients who received:
- •A COVID-19 vaccine within 7 days of Cycle 1 Day
- •Live vaccines or live-attenuated vaccines within 28 days prior to Cycle 1 Day
- •Known active infection of HBV/BCV/HIV.
- •Patients requiring systemic treatment with corticosteroids or other immunosuppressive medications (>10 mg/day prednisone or equivalent).
- •Second primary malignancy not in remission for greater than 3 years.
- •History(within the last 5 years) or risk of autoimmune disease.
- •Pregnant or breastfeeding females.
- •Childbearing potential who does not agree to the use of contraception during the treatment period.
研究组 & 干预措施
ADG126 mono dose escalation
ADG126 monotherapy dose escalation will be traditional 3+3 cohort design.
干预措施: ADG126 Mono (Biological)
ADG126 mono dose expansion
Monotherapy dose expansion is designed to evaluate the preliminary antitumor activity of ADG126 at RP2D or the doses approved by the SRC.
干预措施: ADG126 Mono (Biological)
ADG126-anti PD1 drug dose escalation
Combination therapy will commence at a dose level lower than the cleared dose from the monotherapy dose escalation arms and approved by the SRC.
干预措施: ADG126-anti PD1 (Biological)
ADG126-anti PD1 drug dose expansion
Combination therapy expansion will commence at RP2D or the dose approved by the SRC.
干预措施: ADG126-anti PD1 (Biological)
ADG126-ADG106 dose escalation
Combination therapy will commence at a dose level lower than the cleared dose from the monotherapy dose escalation arms and approved by the SRC.
干预措施: ADG126-ADG106 (Biological)
ADG126-ADG106 dose expansion
Combination therapy expansion will commence at RP2D or the dose approved by the SRC.
干预措施: ADG126-ADG106 (Biological)
结局指标
主要结局
Number of participants with adverse events as assessed by CTCAE v5.0 ADG126-ADG106 combination regimens
时间窗: From first dose of ADG126 (Week 1 Day 1) to 90 days post last dose
Number of participants experiencing dose-limiting toxicities escalating dose levels in adults with advanced / metastatic solid tumors
时间窗: From first dose of ADG126 (Week 1 Day 1) until 21 days
次要结局
- Time to maximum (peak) plasma concentration (Tmax)(From first dose (Cycle 1 Day 1, ) until the last dose (up to 2 years))
- Trough plasma concentration (Ctrough)(From first dose (Cycle 1 Day 1, ) until the last dose (up to 2 years))
- Area under the time concentration curve (AUC) from time zero to infinity (AUC0-inf)(From first dose (Cycle 1 Day 1, ) until the last dose (up to 2 years))
- Antidrug antibodies (ADAs)(From first dose (Cycle 1 Day 1, ) until the last dose (up to 2 years))
- Maximum (peak) plasma concentration (Cmax)(From first dose (Cycle 1 Day 1, ) until the last dose (up to 2 years))