A Phase I, Open-label, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of HS-20089 in Patients With Advanced Solid Tumors
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
- Maximum Tolerated Dose of HS-20089
研究概览
简要总结
HS-20089 is a novel DAR-6 antibody-drug conjugate （ADC） targeting B7-H4. In preclinical studies, it inhibited tumor cell growth expressing B7-H4 in vitro and in vivo. The first-in-human trial is conducted to assess the maximum tolerated dose (MTD) and dose limiting toxicity (DLT), to evaluate the pharmacokinetics, safety and preliminary anti-tumor activity of HS-20089 in Patients With Advanced Solid Tumors.
详细描述
This is a Phase 1a/1b open-label, multicenter study with dose escalation and dose expansion cohorts to evaluate the safety, tolerability, PK and preliminary efficacy of HS-20089 in patients with advanced solid tumors.
The Dose Escalation will include an initial accelerated titration design followed by a Bayesian optimal interval (BOIN) design. Enrollment into Dose Expansion will begin after identification of the MTD and/or MAD in Phase 1a. In Phase 1b, preliminary efficacy will be evaluated in planned expansion cohorts that include patients with specific tumor types that are B7-H4+ advanced solid tumors.
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
- •Men or women aged more than or equal to (≥) 18 years
- •Advanced solid tumor patients confirmed by histology or cytology for who that standard treatment is invalid, unavailable or intolerable
- •Patients have at least one target lesion according to RECEST 1.
- •The requirements for target lesions are: measurable lesions without local treatment such as irradiation, or with definite progress after local treatment, with the longest diameter ≥ 10 mm in the baseline period (in case of lymph nodes, the shortest axis ≥ 15 mm is required)
- •ECOG performance status was 0-1 and did not deteriorate in the previous 2 weeks
- •Estimated life expectancy greater than (>) 12 weeks
- •Females should be using adequate contraceptive measures throughout the study; should not be breastfeeding at the time of screening, during the study and until 3 months after completion of the study; and must have evidence of non-childbearing potential
- •Sign Informed Consent Form
排除标准
- •Treatment with any of the following:
- •Previous or current treatment with drugs targeting B7-H4
- •Any cytotoxic chemotherapy, investigational agents or anticancer drugs within 28 days of the first dose of study drug
- •Radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study drug, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks of the first dose.
- •Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of study drug.
- •Known and untreated, or active central nervous system metastases.
- •Existing abnormal CTCAE≥grade 2 resulted from previous treatment
- •History of other malignancy
- •Inadequate bone marrow reserve or organ function
- •Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV), unless the hepatitis is considered to be cured, Known history of HIV
- •History of hypersensitivity to any active or inactive ingredient of HS-
- •Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
- •Any disease or condition that, in the opinion of the investigator, would compromise the safety of the patient or interfere with study assessments.
研究组 & 干预措施
HS-20089 (Phase Ia：Dose escalation )
HS-20089 for IV infusion of various dose strengths administered in 21 day dosing cycles.
干预措施: HS-20089 (Phase Ia：Dose escalation ) (Drug)
结局指标
主要结局
Maximum Tolerated Dose of HS-20089
时间窗: 3 weeks after initiation of treatment
To determine the MTD for further evaluation of IV administration of HS-20089 in subjects with advanced solid tumors.
次要结局
- Incidence and severity of treatment-emergent adverse events(Baseline through study completion(90 days after last dose))
- Observed maximum plasma concentration (Cmax) after single dose of HS-20089(From pre-dose to 120 hours after single dose on Day 1)
- Observed maximum plasma concentration (Cmax ss) after multiple dose of HS-20089(From pre-dose to 24 hours after the dose on Day 1 of the 21-Day cycle of therapy)
- Apparent terminal half-life (t1/2) after single dose of HS-20089(From pre-dose to 120 hours after single dose on Day 1)
- Area under plasma concentration versus time curve from zero to the 24-hour sampling time (AUC0-24) after single dose of HS-20089(From pre-dose to 24 hours after single dose on Day 1)
- Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) after single dose of HS-20089(From pre-dose to 120 hours after single dose on Day 1)
- Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞) after single dose of HS-20089(From pre-dose to 120 hours after single dose on Day 1)
- To further evaluation of the anti-tumor activity of HS-20089 by assessment of objective response rate (ORR)(From the date of first occurrence of complete response (CR) or partial response (PR) on 2 consecutive occasions (≥4 weeks), until the date of disease progression or withdrawal from study，up to 2 years)
- Anti-drug Antibodies (ADA) of HS-20089(Baseline through study completion(90 days after last dose))