A Study of QL1604 Plus Chemotherapy in Subjects With Stage IVB, Recurrent, or Metastatic Cervical Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Percentage of patients with adverse events
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of PD-1 Inhibitor (QL1604) plus chemotherapy in patients with Stage IV, recurrent, or metastatic cervical cancer. Possible chemotherapy regimens include: paclitaxel plus cisplatin and paclitaxel plus carboplatin.
详细描述
The study will be conducted in 2 parts.The first stage is a single-arm clinical trial, and the second stage is a controlled clinical trial.
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
- •Age ≥ 18 years and ≤ 75 years
- •Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life expectancy of at least 12 weeks.
- •At least one measurable lesion (according to RECIST v1.1)
- •Cervical squamous cell carcinoma, adenocarcinoma and adenosquamous cell carcinoma diagnosed by histopathology and confirmed by imaging as recurrent or stage ⅣB cervical cancer.
- •No brain metastasis, or no meningeal metastasis.
- •Patients must have normal function as defined:
- •ANC≥1.5*10^9/L; PLT≥90*10^9/L, Hb≥90 g/L,
- •Total Bilirubin (TBIL)≤1.5*Upper Limit of Normal(ULN), Alanine Transaminase (ALT)and Aspartate Aminotransferase(AST)≤2.5*ULN.For liver metastasis patients, ALT and AST≤5*ULN,
- •Cr≤ 1.5*ULN, or creatinine clearance rate ≥50 mL/min,
- •Proteinuria <2+，if proteinuria≥ 2+ and 24 hours total urine protein < 1.0 g
- •Any unresolved AEs ≤ CTCAE Grade 1 (except alopecia).
- •Negative pregnancy test for females of child-bearing potentials.
- •Patients with reproductive function agreed to take effective contraceptive measures during the treatment and in 6 months after the end of administration.
- •Patients must be able to understand and volunteer to sign the informed consent.
排除标准
- •Has received more than 2 courses of palliative chemotherapy for treatment of cervical cancer.
- •Has received prior chemoradiotherapy within 3 months before enrollment,or has received prior radiotherapy within 2 weaks before enrollment.
- •Has received prior surgery therapy within 2 weaks before enrollment,or has not recovered from the effects of surgery therapy.
- •Is currently participating in or has participated in a study of an investigational agent within 4 weeks before enrollment.
- •Has any active autoimmune diseases or a history of autoimmune diseases (such as the following, but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, thyroid hyperfunction; patients with vitiligo; complete remission of asthma in childhood, can be included without any intervention after adulthood; asthma patients who require bronchodilators for medical intervention cannot be included).
- •Is using immunosuppressive agents or systemic hormonal therapy to achieve immunosuppressive purposes (agents amount > 10 mg / day of prednisone or other therapeutic hormones), and continue to use within 2 weeks before enrollment.
- •Known history of hypersensitivity to macromolecular protein preparation or any components of the QL1604 formulation, or any components of the study drugs.
- •Has uncontrolled clinically significant cardiac and cerebral vascular diseases within 6 months before enrollment, including but not limited to the following: myocardial infarction, severe or unstable angina, coronary artery/peripheral artery bypass grafting, congestive heart failure, cerebrovascular accident (including transient ischemic attack).
- •Symptomatic congestive heart failure (New York Heart Association Grade II-IV), or NCI-CTCAE v5.0 ≥ 2 arrhythmia, atrial fibrillation of any grade, or clinically significant supraventricular arrhythmia or ventricular arrhythmia requirement for treatment or intervention.
- •Has active infection or an unexplained fever > 38.5°C during screening visits( subjects with tumor fever may be enrolled at the discretion of the investigator).
- •Hepatitis b surface antigen (HBsAg) positive and/or hepatitis b core antibody (HBcAb) positive and HBVDNA>103copies/ml, hepatitis c virus antibody positive .
- •Known history of human immunodeficiency virus (HIV) infection, or other acquired or congenital immunodeficiency diseases,or has a history of organ transplantation (except corneal transplantation).
- •Has been vaccinated with live anti-tumor vaccine, or have received anti-tumor immunotherapy, or may receive other systemic anti-tumor treatments during the study period.
- •Peripheral neuropathy≥ CTCAE Grade
- •History of psychotropic substance abuse, alcoholism or drug abuse.
- •Has a clear history of neurological or mental disorders, including epilepsy or dementia.
- •Patients with other malignancies witnin 5 years( except cured basal cell carcinoma of skin cancer, papillary thyroid carcinoma).
- •At the discretion of the investigator, there are patients with serious concomitant disease that compromises patient safety or affects the patient's completion of the study,such as unable to be controlled within normal level following treatment of anti-hypertension agents (systolic blood pressure > 160 mmHg, diastolic blood pressure > 110 mmHg), serious diabetes, thyroid diseases, etc.
研究组 & 干预措施
QL1604+Chemotherapy
On Day 1 of each 21-day cycle, participants receive an intravenous (IV) infusion of QL1604 200 mg plus Investigator choice of chemotherapy (paclitaxel 175 mg/m^2 plus cisplatin 70 mg/m^2 or paclitaxel 175 mg/m^2 plus carboplatin Area Under the Curve (AUC) 6)
干预措施: QL1604 (Drug)
QL1604+Chemotherapy
On Day 1 of each 21-day cycle, participants receive an intravenous (IV) infusion of QL1604 200 mg plus Investigator choice of chemotherapy (paclitaxel 175 mg/m^2 plus cisplatin 70 mg/m^2 or paclitaxel 175 mg/m^2 plus carboplatin Area Under the Curve (AUC) 6)
干预措施: Paclitaxel injection (Drug)
QL1604+Chemotherapy
On Day 1 of each 21-day cycle, participants receive an intravenous (IV) infusion of QL1604 200 mg plus Investigator choice of chemotherapy (paclitaxel 175 mg/m^2 plus cisplatin 70 mg/m^2 or paclitaxel 175 mg/m^2 plus carboplatin Area Under the Curve (AUC) 6)
干预措施: Cisplatin/Carboplatin (Drug)
结局指标
主要结局
Percentage of patients with adverse events
时间窗: Up to 90 days from last dose
The incidence and severity of adverse events (AE),serious adverse events (SAE) and treatment-emergent adverse events (TEAEs) according to CTCAE V5.0
Objective response rate (ORR) as assessed by investigator based on RECIST v1.1 and iRECIST
时间窗: approximately 2 years
Objective response rate (ORR) as assessed by investigator based on RECIST v1.1 and iRECIST
次要结局
- Cmax of QL1604(approximately 1 years)
- Tmax of QL1604(approximately 1 years)
- Overall survival(OS)(approximately 2 years)
- Time to progress (TTP)(approximately 2 years)
- Cmin of QL1604(approximately 1 years)
- Progression-free survival (PFS) as assessed by investigator based on RECIST v1.1 and iRECIST(approximately 2 years)
- Duration of response(DOR)(approximately 2 years)
- AUC of QL1604(approximately 1 years)
- Vss of QL1604(approximately 1 years)
- CLT(total body clearance) of QL1604(approximately 1 years)
- Immunogenicity(approximately 1 years)
- T1/2 of QL1604(approximately 1 years)