An Open-label, Phase I Trial of SIM1811-03 to Assess the Safety, Efficacy and Pharmacokinetics/Pharmacodynamics in Subjects With Advanced Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 255
- 试验地点
- 1
- 主要终点
- Part I The maximum tolerated dose (MTD) or recommended dose (RD)
研究概览
简要总结
This is a first in human, open-label, dose escalation and expansion Phase I study of SIM1811-03 in adult patients with advanced tumors. SIM1811-03 is a first-in-class IgG1-based humanized anti-tumor necrosis factor type 2 receptor (TNFR2) monoclonal antibody for the treatment of malignant tumors.
详细描述
This is a phase I trial to evaluate the safety, efficacy, and pharmacokinetic/ pharmacodynamic characteristics of SIM1811-03 in participants with advanced tumors.
The trial is composed of two parts, Part I and Part II. Part I is a dose escalation part to determine the MTD and/or RD of SIM1811-03 or SIM1811-03 in combination with Sintilimab Injection . Part II is a dose expansion part at RD level SIM1811-03 determined in Part I to assess the anti-tumor activity of SIM1811-03 or SIM1811-03 in combination with Sintilimab Injection in participants with advanced solid tumors or CTCL. The tumor types in Part II will be adjusted based on the response observed in Part I.
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
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
- •Written informed consent must be obtained prior to any procedures that are not considered standard of care.
- •≥18 years old on the day of signing informed consent, male or female;
- •Histologically and/or cytologically documented advanced/metastatic solid tumors or histologically confirmed CTCL;
- •Have relapsed or refractory advanced solid tumors or CTCL, whose disease has progressed during or after standard therapy
- •At least one measurable tumor lesion (RECIST 1.1) for participants with solid tumors. Tumor lesions previously treated with radiotherapy or local therapy should not be considered as measurable unless progression is documented.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
- •Life expectancy of ≥ 12 weeks.
- •Adequate organ and marrow functions 9） Provide archived or fresh biopsy tumor tissue samples or tissue sections
- •Females of childbearing potential require strict contraception during the study.
排除标准
- •Participated in an interventional clinical trial or has used investigational devices within 28 days prior to first dose of study drug or received systemic anti-cancer treatments.
- •2）Toxicity due to previous antineoplastic therapy has not recovered to grade 0 or 1 unless such AEs are not considered to pose safety risks.
- •Required use of corticosteroids for more than 7 consecutive days within 14 days prior to the first dose of study treatment.
- •Participated with active or history of or risk of autoimmune disease 5) Major surgery (except biopsy) or unhealed wound within 4 weeks prior to first dose of study drug.
- •Other known malignancies within 2 years prior to enrollment. 7) Has known active central nervous system (CNS) metastases. 8) History of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis, symptomatic interstitial lung disease or evidence of active pneumonia that is not considered appropriate by the investigator.
- •Participants with a history of active pulmonary tuberculosis infection within 1 year prior to first dose of study drug.
- •History of hemorrhagic disease requiring transfusion within the last 3 months.
研究组 & 干预措施
SIM1811-03 monotherapy or SIM1811-03 in combination with Sintilimab injection
All participants receive SIM1811-03 or SIM1811-03 in combination with Sintilimab injection
干预措施: SIM1811-03 or in combination with Sintilimab injectiont (Drug)
结局指标
主要结局
Part I The maximum tolerated dose (MTD) or recommended dose (RD)
时间窗: Within 28 days after the first dose in Q2W; Within 21 days after the first dose in Q3W
Part I (dose escalation): To estimate the maximum tolerated dose (MTD) or recommended dose (RD) of SIM1811-03 Monotherapy or in combination with sintilimab
Part II ORR for Solid Tumor
时间窗: Q2W: Participants will be evaluated every 8 weeks from baseline to Treatment Cycle 12 (an average of 1 year); Q3W:Participants will be evaluated every 6 weeks from baseline to Treatment Cycle 12 (an average of 1 year)
Solid tumors: objective response rate (ORR) assessed by Investigator per RECIST 1.1 from baseline to disease progression
Part II ORR for CTCL
时间窗: Q2W:Participants will be evaluated every 8 weeks from baseline to Treatment Cycle 12 (an average of 1 year); Q3W:Participants will be evaluated every 6 weeks from baseline to Treatment Cycle 12 (an average of 1 year)
CTCL: ORR assessed by Investigator per global response score
次要结局
- Antidrug antibodies of SIM1811-03 and Sintilimab(before staring the treatment for the first 7 treatment cycles (each cycle would be 28 days/21 days))
- Neutralizing antibodies of SIM1811-03 and Sintilimab(before staring the treatment for the first 7 treatment cycles (each cycle would be 28 days/21 days))
- safety and tolerability (incidence of AE and SAE)(All AEs/SAEs will be collected in this study from the time the subject signs the informed consent form until 90 days after the last dose)
- Pharmacokinetics profile of SIM1811-03 and in combination with Sintilimab(Collection point would Predose, 0 hour, 24 hours, 168hours, 336 hours post-dose from Cycle 1 to Last dose (an average of 1 year))