NCT06769152招募中2 期
A Phase II Clinical Study to Evaluate the Efficacy and Safety of HLX43 (Anti-PD-L1 ADC) in Patients With Recurrent/Metastatic Gynecological Malignant Tumors Failed or Intolerance to Standard First-Line Therapy
Shanghai Henlius Biotech2 个研究点 分布在 1 个国家目标入组 190 人开始时间: 2025年2月20日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 190
- 试验地点
- 2
- 主要终点
- ORR
研究概览
简要总结
The study is being conducted to explore the reasonable dosage and evaluate the efficacy, safety and tolerability of HLX43 (Anti-PD-L1 ADC) in patients with recurrent/metastatic cervical cancer or ovarian cancer failed or intolerance to standard first-line therapy.
详细描述
This study is an open-label phase II clinical study to explore the reasonable dosage and evaluate the efficacy, safety and tolerability of HLX43 (Anti-PD-L1 ADC) in patients with recurrent/metastatic cervical or ovarian cancer failed or intolerance to standard first-line therapy.
In this study, eligible subjects will be randomized at 1:1:1 ratio, and the patients will be administered with HLX43 at different doses via intravenous infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- Female
- 接受健康志愿者
- 否
入选标准
- •Volunteer to participate in clinical research; To fully understand and understand this study and to sign the Informed Consent Form (ICF); Willing to follow and able to complete all test procedures;
- •The age of signing ICF is ≥ 18 years old and ≤ 75 years old;
- •Cohort 1: Metastatic or recurrent cervical cancer including squamous cell, adenocarcinoma or adenosquamous histology confirmed by histopathology or cytology.
- •Cohort 2: Histologically confirmed high-grade serous ovarian, fallopian tube, or primary peritoneal cancer.
- •Cohort 1: Previous failure or progression of standard systemic therapy for cervical cancer (For patients with PD-L1 expression positive [CPS≥1], the standard therapy is defined as platinum-based chemotherapy in combination with immune checkpoint inhibitor (ICI) therapy; for patients with PD-L1 expression negative [CPS<1], the standard therapy is defined as platinum-based chemotherapy), or intolerability toxicity (CTCAE≥3 adverse events), or contraindications to standard therapy.
- •Cohort 2: Ovarian cancer patients with platinum-resistant disease: If the patient has previously received only first-line platinum-based chemotherapy, platinum resistance is defined as having received at least 4 cycles of platinum-based chemotherapy, with the tumor showing a response to platinum-based chemotherapy (best tumor assessment being complete remission/partial remission), and the time from the last platinum-based chemotherapy to tumor progression being >3 months and ≤6 months. If the patient has previously received multiple lines of platinum-based chemotherapy, platinum resistance is defined as disease progression occurring during the last line of platinum-based chemotherapy treatment or within 6 months after the last platinum-based chemotherapy.
- •Within 4 weeks prior to the first administration of the medication, at least one measurable target lesion must be evaluated according to the RECIST v1.1 criteria;
- •Tumor tissue should be provided as much as possible for an evaluable PD-L1 expression result at Screening period；
- •Before the initial administration of the study drug, there should be at least a 3-week interval or 5 times the half-life of the last cytotoxic chemotherapy, immunotherapy, or biological therapy, whichever is shorter. There should be at least a 2-week interval from the previous small molecule targeted therapy, at least a 1-week interval from traditional Chinese medicine treatment with antitumor indications or minor surgery. Additionally, treatment-related adverse events (AEs) should have recovered to NCI-CTCAE grade ≤ 1 (except for grade 2 peripheral neurotoxicity and alopecia)；
- •The ECOG physical performance score of 0-1 in the week prior to randomization；
- •Expected survival ≥ 3 months；
- •Laboratory tests within the previous week confirm adequate organ function (within 14 days prior to the first dose of medication, without receiving interventions such as blood transfusions or granulocyte colony-stimulating factor)；
- •Female subjects of childbearing potential must agree to use at least one highly effective method of contraception during the trial and for at least 6 months after the last dose of the study drug. Female subjects of childbearing potential must have a negative pregnancy test within 7 days prior to enrollment.
排除标准
- •History of any second malignant tumor within the first 2 years prior to randomization;
- •Subjects who are preparing for or have previously received an organ or bone marrow transplant;
- •Symptomatic, untreated, or progressively worsening central nervous system (CNS) or leptomeninges metastases;
- •After appropriate intervention, uncontrollable pleural effusion, pericardial effusion or ascites still need to be drained frequently;
- •Present with grade ≥1 radiation pneumonia as defined by RTOG/EORTC; A history of interstitial lung disease (ILD) or imaging findings during screening that suggest such disease is suspected; Or there are lung diseases leading to clinical severe respiratory impairment;
- •Subjects exhibit poorly controlled cardiovascular clinical symptoms or diseases, including but not limited to: (1) NYHA class II or above heart failure, or left ventricular ejection fraction (LVEF) < 50%; (2) unstable angina; (3) myocardial infarction or cerebrovascular accident within the last 6 months (excluding lacunar infarction, minor ischemic stroke, or transient ischemic attack); (4) uncontrolled arrhythmias (including QTc interval ≥ 450 ms for males, ≥ 470 ms for females) (QTc interval calculated by Fridericia's formula); (5) poorly controlled hypertension (systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg despite active treatment);
- •Previous occurrence of adverse events leading to permanent discontinuation of immunotherapy; or A history of ≥ Grade 2 immune-related pneumonia or myocarditis;
- •Active or suspected autoimmune disease. Patients with autoimmune-related hypothyroidism who are undergoing thyroid hormone replacement therapy are permitted to participate in the study; patients with controlled Type 1 diabetes mellitus receiving insulin therapy are also allowed to participate in the study;
- •Received systemic corticosteroids (prednisone >10 mg/day or an equivalent dose of similar drugs) or other immunosuppressive treatments within 14 days prior to the first dose; with the following exceptions: use of topical, ophthalmic, intra-articular, intranasal, and inhaled corticosteroids; short-term use of corticosteroids for prophylactic treatment during situations such as the use of contrast agents;
- •Within the 2 weeks prior to randomization, there is the presence of an active systemic infectious disease requiring intravenous antibiotic treatment;
- •Live vaccinations or attenuated live vaccinations should not be administered within 4 weeks prior to the initial dosing. Administration of inactivated viral vaccines for seasonal influenza is permitted;
- •Used strong inhibitors or strong inducers of CYP2D6 or CYP3A within 2 weeks prior to randomization;
- •Known history of severe allergic reactions to macromolecular protein preparations/monoclonal antibodies, or allergy to components of the trial drug formulation; Previously received ADC drugs with topoisomerase I inhibitors as toxins.
- •Active tuberculosis;
- •Human immunodeficiency virus (HIV) infection;
- •Active Hepatitis B or Hepatitis C virus (HBV or HCV) infection or HBV/HCV co-infection;
- •Pregnant or lactating women;
- •The researcher deems that the subject has any other factors that make them unsuitable for participation in this trial.
研究组 & 干预措施
HLX43 2.0mg/kg
Experimental
every 3 weeks (Q3W)
干预措施: HLX43 (Drug)
HLX43 2.5mg/kg
Experimental
every 3 weeks (Q3W)
干预措施: HLX43 (Drug)
HLX43 3.0mg/kg
Experimental
every 3 weeks (Q3W)
干预措施: HLX43 (Drug)
HLX43 3.0mg/kg loading dose
Experimental
every 3 weeks (Q3W)
干预措施: HLX43 (Drug)
结局指标
主要结局
ORR
时间窗: up to 24 week
Objective response rate (ORR) (assessed by INV according to the RECIST v1.1 criteria)
PFS
时间窗: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 14 months
Defined as the time (in months) from randomization to the first confirmed and documented progressive disease or death (whichever occurs first) as assessed by INV according to the RECIST v1.1 criteria.
次要结局
- ORR(up to 24 weeks)
- PFS(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 14 months)
- OS(From randomization to death from any cause (up to approximately 36 months))
- Incidence and severity of adverse events (AEs)(time from the date of the first dose of study drug until the date of death from any cause, assessed up to 24 months)
研究者
研究点 (2)
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