A Phase I Open-label Clinical Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of AK127 Monotherapy in Patients With Advanced Malignant Tumors
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 36
- 主要终点
- Number of participants with adverse events (AEs)
研究概览
简要总结
This study is to characterize the safety, tolerability and anti-tumor activity of AK127 as a single agent in adult subjects with advanced solid tumor malignancies.
详细描述
This study is to characterize the safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) and anti-tumor activity of AK127 as a single agent in adult subjects with advanced solid tumor malignancies. The study, as a dose escalation phase is to determine the maximum tolerated dose (MTD), or recommended Phase 2 dose (RP2D) for AK127 as a single agent, and describe Dose Limiting Toxicity (DLT).
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability to understand and voluntarily sign a written informed consent form (ICF), which must be signed before the specified study procedures required for the study are performed.
- •Males or females aged ≥ 18 to ≤ 75 years at the time of signing informed consent.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or
- •Life expectancy ≥3 months.
- •Histologically or cytologically documented advanced or metastatic solid tumor that is refractory/relapsed to standard therapies, or for which no effective standard therapy is available, or the subject is not suitable for standard therapy.
- •Adequate organ function.
- •Patients of childbearing potential must agree to use effective contraceptive measures.
排除标准
- •The patient has received prior immunotherapy against TIGIT target.
- •Not currently enrolled in any other clinical study.
- •Receipt of any anticancer therapy within 4 weeks or within 5 half-lives of the drug prior to the first dose of AK
- •Symptomatic central nervous system metastases.
- •Active malignancies within the past 1 years, with the exception of tumors in this study and cured local tumors.
- •Active autoimmune disease requiring systemic treatment prior to the start of study treatment.
- •There is a history of major diseases 1 year prior to the first dose.
- •Medical history of gastrointestinal perforation or gastrointestinal fistula within 6 months prior to the first dose.
- •Received chest radiation therapy prior to the first dose.
- •Presence of clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring frequent drainage.
- •Active or previously documented inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis).
- •Receipt of live or attenuated vaccination within 4 weeks prior to the first dose of AK
- •Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
- •Known history of active tuberculosis.
- •History of organ transplant or hematopoietic stem cell.
- •History of primary immunodeficiency.
- •Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results.
- •Other cases deemed inappropriate by the investigator.
研究组 & 干预措施
AK127
Subjects will receive AK127 by intravenous administration
干预措施: AK127 (Drug)
结局指标
主要结局
Number of participants with adverse events (AEs)
时间窗: From the subject signs the ICF to 30 days (AE) and 90 days (SAE) after the last dose of study treatment or initiation of other anti-tumor therapy, whichever occurs first
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment
Number of participants with a Dose Limiting Toxicity (DLT)
时间窗: During the first 21 days
DLTs will be assessed during the first 21 days of treatment for dose-escalation phase and are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected or definite relationship to study drug
次要结局
- ORR(Up to 2 years)
- PFS(Up to 2 years)
- Area under the Concentration-Time Curve (AUC) of AK127(Cycle 1 and 4: Predose, Post-dose-5min,2 hours, 24 hours, Day 4,8 and 15; Cycle 2,3,5,6: Predose and Post-dose-5min; then Predose at Day 1, every 2 cycles (cycle length 21 days),Day30 after last dose; Up to 2 years and 1 months)
- Maximum observed concentration (Cmax) of AK127(Cycle 1 and 4: Predose, Post-dose-5min,2 hours, 24 hours, Day 4,8 and 15; Cycle 2,3,5,6: Predose and Post-dose-5min; then Predose at Day 1, every 2 cycles (cycle length 21 days),Day30 after last dose; Up to 2 years and 1 months)
- DCR(Up to 2 years)
- DOR(Up to 2 years)
- TTR(Up to 2 years)
- Minimum observed concentration (Cmin) of AK127 at steady state(Cycle 1 and 4: Predose, Post-dose-5min,2 hours, 24 hours, Day 4,8 and 15; Cycle 2,3,5,6: Predose and Post-dose-5min; then Predose at Day 1, every 2 cycles (cycle length 21 days),Day30 after last dose; Up to 2 years and 1 months)
- Number and Percentage of Subjects with Anti-Drug Antibodies(ADAs) to AK127(Predose on Day 1 at Cycle 1-6, then Predose at Day 1, every 2 cycles,Day30 after last dose; Up to 2 years and 1 months)