A Multi-center, Open-label, Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumor Efficacy of GenSci140 in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 170
- 试验地点
- 1
- 主要终点
- maximal tolerance dose （MTD）
研究概览
简要总结
This is a phase I, multi-center, open-label, dose-escalation (Part 1) and dose-expansion (Part 2) first-in-human study in China to evaluate the safety, tolerability, PK profile and efficacy of GenSci140 in participants with advanced solid tumors, and to determine the MTD (if any) and RDE. The dose-expansion study aims to evaluate the efficacy, safety and PK profile of GenSci140 in the treatment of ovarian cancer or other FRα-positive advanced solid tumors at different dose levels, and to select an appropriate RP2D (if applicable).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Those who are able to understand and willing to sign written Informed Consent Form.
- •Aged between 18 and 75 years (inclusive) when signing the ICF
- •Participants with advanced solid tumors
- •The participant agrees to provide fresh biopsy or archived tumor tissues for testing by the central laboratory.
- •At least one evaluable lesion in the dose-escalation part, and at least one measurable lesion in the dose-expansion part.
- •Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or
- •Life expectancy ≥ 3 months.
- •Adequate hematologic and organ function before the first dose of GenSci
- •All toxicities related to prior anti-tumor therapies must have resolved to Grade ≤ 1, with the following exceptions: alopecia, peripheral neurotoxicity (must have resolved to Grade ≤ 2).
- •For participants with congestive heart failure (CHF), it must be Grade ≤ 1 in severity and must have recovered completely prior to enrollment.
- •Normal QT interval on electrocardiogram (ECG) evaluation at screening
- •Participants who test negative for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV).
- •Women of childbearing potential (WOCBP) must have a negative serum pregnancy test result. WOCBP must agree to avoid pregnancy.
- •Men with female partners of childbearing potential must take appropriate precautions to avoid pregnancy of partner and use appropriate barrier contraceptives or abstinence
排除标准
- •Past history of cancers.
- •Symptomatic primary central nervous system (CNS) tumors, metastases, leptomeningeal carcinomatosis, or therapy naive spinal cord compression.
- •Use of an investigational medicinal product (IMP) or antitumor therapy (including chemotherapy, biologic therapy, immunotherapy) within 5 half-lives or 4 weeks before the first dose of GenSci
- •Concomitant anti-tumor therapy is not permitted
- •Major surgery within 4 weeks prior to the first dose of GenSci
- •Radiotherapy for ≥ 20% of bone marrow or large area of radiotherapy within 4 weeks prior to the first dose of GenSci
- •Or participants have not recovered from acute effects of radiotherapy to baseline prior to the first dose of GenSci
- •Clinically significant active cardiovascular disorder or history of myocardial infarction within 6 months prior to the first dose of GenSci
- •Uncontrolled active systemic bacterial, viral, or fungal infection or ongoing serious systemic disease, such as hypertension or diabetes, despite Best Supportive Care. Chronic disease screening is not required.
- •History of multiple sclerosis or other demyelinating diseases, Eaton-Lambert syndrome (paraneoplastic syndrome), alcoholic liver disease, history of internal haemorrhage or ischemic stroke within the past 6 months, haemorrhagic diathesis that are unsuitable for enrollment as assessed by the investigator.
- •Suspected treatment-related pneumonitis that was clinically diagnosed in the past and currently requires steroids or cannot be ruled out by imaging at screening.
- •Uncontrolled pleural effusion, pericardial effusion, or abdominal and pelvic fluid collection requiring drainage and/or diuretics within 14 days prior to the first dose of GenSci
- •Pregnant or lactating women.
- •Known hypersensitivity to prior monoclonal antibody therapy.
- •Patients who previously underwent allogeneic or autologous bone marrow transplantation.
- •Participants whom the investigator deems unsuitable for enrollment in this clinical study
研究组 & 干预措施
Dose Level 1~ Dose Level 5
Participants who meet the inclusion criteria and do not meet the exclusion criteria will be sequentially enrolled into five pre-specified doses for dose groups 1-5.
干预措施: GenSci140 for Injection (Drug)
Cohort 1~ Cohort 4
Cohort 1: Cohort 1 is planned to be conducted in patients with ovarian cancer. Cohort 2: FRα-positive endometrial cancer. Cohort 3: FRα-positive lung cancer. Cohort 4: FRα-positive triple negative breast cancer.
干预措施: GenSci140 for Injection (Drug)
结局指标
主要结局
maximal tolerance dose （MTD）
时间窗: up to 3 months
To determine the MTD (if any) of GenSci140 in participants with advanced solid tumors
recommended dose of expansion （RDE）
时间窗: up to 3 months
To determine the RDE of GenSci140 in participants with advanced solid tumors
Incidence and severity of adverse event (AEs), and incidence of dose limiting toxicities（DLTs）
时间窗: 3 weeks
To determine the MTD (if any) of GenSci140 in participants with advanced solid tumors
objective response rate（ORR）
时间窗: up to 5 months
To evaluate the preliminary efficacy of GenSci140 in participants with advanced solid tumors
duration of response（DOR）
时间窗: up to 5 months
To evaluate the preliminary efficacy of GenSci140 in participants with advanced solid tumors
disease control rate（DCR）
时间窗: up to 5 months
To evaluate the preliminary efficacy of GenSci140 in participants with advanced solid tumors
Incidence and severity of adverse event (AEs)
时间窗: up to 5 months
To evaluate the safety and tolerability of GenSci140 at specific doses in participants with specific advanced solid tumors.
次要结局
未报告次要终点