A Prospective, Single-Arm, Phase II Trial of QL1706 in Patients With Recurrent and/or Metastatic Cervical Cancer Who Had Developed Resistance to Prior PD-1/PD-L1 Antibody Therapy
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 50
- 主要终点
- ORR
研究概览
简要总结
To explore the efficacy and safety of administrating QL1706 in patients with recurrent and/or metastatic cervical cancer who had developed resistance to prior PD-1/PD-L1 antibody therapies.
详细描述
The application of PD-1/PD-L1 antibodies in cervical cancer is becoming increasingly widespread. However, monotherapy with PD-1 inhibitors demonstrates only a 10-20% response rate and a median progression-free survival of merely 2 months in patients with recurrent or metastatic cervical cancer. To address the issue of resistance to PD-1/PD-L1 antibodies in cervical cancer patients, we plan to conduct a clinical study. This study will administer a PD-1/CTLA-4 bispecific antibody to patients with recurrent or metastatic cervical cancer who are resistant to PD-1/PD-L1 therapy, thereby evaluating the efficacy and safety profile of the bispecific antibody in this specific patient population.
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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients with recurrent/metastatic cervical cancer who previously experienced failure of PD-1 blockade therapy;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
- •Life expectancy ≥3 months;
- •At least one measurable lesion per RECIST v1.1:
- •Non-lymph node lesion: Longest diameter ≥10 mm Lymph node lesion: Short-axis diameter ≥15 mm Note: Previously irradiated lesions must be outside radiation fields or demonstrate progression post-radiation.
- •Adequate organ function within 14 days prior to treatment:
- •Absolute neutrophil count (ANC) ≥1.0×10⁹/L
- •Hemoglobin ≥60 g/L
- •Platelet count ≥50×10⁹/L
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3×ULN (≤5×ULN for hepatic metastasis)
- •Serum creatinine ≤2×ULN
- •Reproductive requirements:
- •Non-childbearing potential (surgically sterilized or postmenopausal) OR
- •Women of childbearing potential:
- •Negative serum pregnancy test within 7 days prior to enrollment Commitment to use double-barrier contraception throughout the study and for 180 days post-treatment
- •Ability to comply with scheduled visits, treatment plans, and laboratory tests;
- •Voluntarily signed written informed consent.
排除标准
- •Prior treatment with anti-PD-1/CTLA-4 bispecific antibodies;
- •Active autoimmune disease requiring systemic control with corticosteroids (≥10 mg/day prednisone equivalent) or immunosuppressants within 14 days prior to enrollment;
- •Clinically significant cardiovascular/cerebrovascular events within 6 months prior to treatment, including:
- •Acute myocardial infarction
- •Unstable angina
- •Cerebrovascular accident
- •Symptomatic arterial/venous thrombosis or ischemic cardiomyopathy
- •Clinically significant ventricular arrhythmias (sustained VT, VF, torsades de pointes)
- •NYHA Class III/IV heart failure
- •QTcF ≥480 ms or congenital long QT syndrome
- •LVEF <50% or severe wall motion abnormality per echocardiography
- •Uncontrolled hypertension (SBP >160 mmHg or DBP >100 mmHg)
- •Other clinically significant arrhythmias (e.g., third-degree AV block);
- •Uncontrolled comorbidities potentially affecting protocol compliance:
- •Severe respiratory diseases (ILD, severe asthma)
- •Active infections:
- •HBV (HBsAg+ AND HBV-DNA >500 IU/mL)
- •HCV (HCV-Ab+ AND HCV-RNA+)
- •Active TB or systemic infections requiring treatment ≤14 days
- •GI perforation/fistula ≤6 months (exceptions: resolved surgically)
- •Clinically significant bleeding ≤1 month (hematemesis, hemoptysis, etc.)
- •Active diverticulitis, abdominal abscess, or bowel obstruction;
- •Other malignancies within 3 years (excluding cured BCC, superficial bladder Ca, DCIS, or papillary thyroid Ca);
- •Known immunodeficiency disorders;
- •History of allogeneic hematopoietic stem cell or solid organ transplantation (excluding corneal grafts);
- •Systemic infections requiring IV antibiotics >7 days within 2 weeks prior to treatment;
- •Administration of live attenuated vaccines within 4 weeks before/after treatment;
- •Pregnancy or lactation;
- •Investigator-assessed ineligibility;
- •Concurrent participation in other clinical trials.
研究组 & 干预措施
PD-1/CTLA-4 bispecific antibody treatment group
Enrolled patients will receive intravenous infusion of QL1706 once every 3 weeks at a dose of 5.0 mg/kg until disease progression, death, intolerable treatment toxicity, or withdrawal from the clinical trial for any reason.
干预措施: QL1706 (bispecific antibody targeting PD-1 and CLTA-4) (Drug)
结局指标
主要结局
ORR
时间窗: 1-year
The objective response rate (ORR) assessed by the Independent Review Committee (IRC) (according to RECIST v1.1).
次要结局
- DOR(1-year)
- OS(1-year)
- Profile of adverse events(3 years)
- DCR(1-year)
- PFS(1-year)
研究者
Zhiyong Yuan
Head of Radiotherapy Department
Tianjin Medical University Cancer Institute and Hospital