ARTEMIS-001: A Phase 1, Open-label, Multi-center Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Multiple Doses of Intravenous Administration of HS-20093 in Patients With Locally Advanced or Metastatic Solid Tumors Who Have Progressed Following Prior Therapy
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 177
- 试验地点
- 1
- 主要终点
- Ⅰa (Dose-Escalation Stage): Maximum tolerated dose (MTD) for HS-20093
研究概览
简要总结
HS-20093 is a fully humanized IgG1 antibody-drug conjugate (ADC) which specifically binds to B7-H3, a target wildly expressed on solid tumor cells. The objectives of this study are to investigate the safety, tolerability, pharmacokinetics and anti-tumor activity of HS-20093 in Chinese advanced solid tumor patients.
This is a phase 1, open-label, multi-center, dose-escalation and expansion study evaluating the safety, tolerability, pharmacokinetic (PK), and the therapeutic potential of HS-20093 as a monotherapy in subjects with advanced solid tumors.
详细描述
This is an open-label, multi-center, dose-escalation and expansion, first-in-human phase 1 study in Chinese adult participants with locally advanced or metastatic solid tumors. This study will consist of two parts: A Part Ia dose escalation stage and a Part Ib dose expansion stage.
The objectives of this study are to evaluate the safety, tolerability, PK and preliminary anti-tumor activity, describe the dose-limiting toxicities (DLTs), and determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) of HS-20093.
Part Ia: Participants with advanced cancer are eligible for dose escalation study if they have progressed on or intolerant to available standard therapies, or no standard or available curative therapy exists. The dose escalation will include an initial accelerated titration design followed by i3+3 design.
Part Ib: Enrollment into dose expansion will begin after identification of the MTD or MAD in Phase Ia. The dose expansion study will be conducted in populations with the following indications: locally advanced or metastatic non- small cell lung cancer (NSCLC)，extensive stage small cell lung cancer (ES-SCLC) and other types of advanced solid tumor.
All patients will be carefully followed for adverse events during the study treatment and for 90 days after the last dose of study drug. Subjects will be permitted to continue therapy with assessments for progression if the product is well tolerated and sustained clinical benefit exists.
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
- •At least age of 18 years at screening;
- •Histologically or cytologically confirmed, locally advanced or metastatic solid tumors for which standard treatment either does not exist or has proven ineffective or unavailable or intolerable
- •At least one extra-cranial measurable lesion according to RECIST 1
- •Agree to provide fresh or archival tumor tissue
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0~1
- •Life expectancy >= 12 weeks
- •Agree to use medically accepted methods of contraception
- •Men or women should be using adequate contraceptive measures throughout the study;
- •Females subjects must not be pregnant at screening or have evidence of non-childbearing potential
- •Signed and dated Informed Consent Form
排除标准
- •Any of the following would exclude the subject from participation in the study:
- •Treatment with any of the following:
- •Previous or current treatment with B7-H3 targeted therapy
- •Any cytotoxic chemotherapy, investigational agents and anticancer drugs within 14 days prior to the first scheduled dose of HS-20093
- •Prior treatment with a monoclonal antibody within 28 days prior to the first scheduled dose of HS-20093
- •Radiotherapy with a limited field of radiation for palliation within 2 weeks, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks prior to the first scheduled dose of HS-20093
- •Major surgery within 4 weeks prior to the first scheduled dose of HS-20093
- •Subjects with previous or concurrent malignancies
- •Inadequate bone marrow reserve or organ dysfunction
- •Evidence of cardiovascular risk
- •Evidence of current severe or uncontrolled systemic diseases
- •Evidence of mucosal or internal bleeding within 1 month prior to the first scheduled dose of HS-20093
- •Known active infection requiring antibodies treatment within 2 weeks, or severe infection within 4 weeks prior to the first scheduled dose of HS-20093
- •Subjects with current infectious diseases
- •History of neuropathy or mental disorders
- •Pregnant or lactating female
- •History of severe hypersensitivity reaction, severe infusion reaction or idiosyncrasy to drugs chemically related to HS-20093 or any of the components of HS-20093
- •Known vaccination or hypersensitivity of any level within 4 weeks prior to the first scheduled dose of HS-20093
- •Unlikely to comply with study procedures, restrictions, and requirements in the opinion of the investigator
- •Any disease or condition that, in the opinion of the investigator, would compromise subject safety or interfere with study assessments
结局指标
主要结局
Ⅰa (Dose-Escalation Stage): Maximum tolerated dose (MTD) for HS-20093
时间窗: Up to day 21 from the first dose
To determine the MTD for further evaluation of IV administration of HS-20093 in subjects with advanced solid tumors.
Ⅰb (Dose-Expansion Stage): Objective response rate (ORR) determined by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
时间窗: From the first dose up to PD or withdrawal from study, whichever came first, assessed up to 24 months
Objective tumor response for target lesions will be assessed by imaging/measurement compared with the overall tumor burden at baseline (Day -28 to -1). ORR is evaluated by the number of participants with best overall response of complete response (CR) and partial response (PR) \[Confirmed CR/PR assessment require at least one repeat (≥4 weeks)\].
次要结局
- Observed maximum plasma concentration (Cmax) of HS-20093 in participants with advanced solid tumor(From pre-dose to 14 days after the first dose on Cycle 1)
- Terminal half-life (T1/2) of HS-20093 following IV dose in participants with advanced solid tumor(From pre-dose to 14 days after the first dose on Cycle 1)
- ORR determined by investigators according to RECIST 1.1 (dose-escalation stage)(From the first dose up to PD or withdrawal from study, whichever came first, assessed up to 24 months)
- Duration of response (DOR) determined by investigators according to RECIST 1.1(From the first dose up to PD or death, whichever came first, assessed up to 24 months)
- Disease control rate (DCR) determined by investigators according to RECIST 1.1(From the first dose up to PD or withdrawal from study, whichever came first, assessed up to 24 months)
- Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) following the first dose of HS-20093(From pre-dose to 14 days after the first dose on Cycle 1)
- Percentage of participants with antibodies to HS-20093 in serum(From pre-dose to 90 days post end of treatment)
- Overall survival (OS) (only in dose expansion stage)(From the randomization/first dose up to death, whichever came first, assessed up to 24 months)
- Incidence and severity of adverse events (AEs)(From the first dose through 90 days post end of treatment)
- Time to reach maximum plasma concentration (Tmax) of HS-20093 following the first dose in participants with advanced solid tumor(From pre-dose to 14 days after the first dose on Cycle 1)
- Progression-free survival (PFS) determined by investigators according to RECIST 1.1(From the randomization/first dose up to PD or death, whichever came first, assessed up to 24 months)