Efficacy and Safety of Iparomlimab and Tuvonralimab (QL1706) in the Treatment of Intermediate Trophoblastic Tumors: A Prospective, Multicenter, Single-arm Trial
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Complete Response (CR) Rate
研究概览
简要总结
This clinical trial aims to evaluate the efficacy and safety of Iparomlimab and Tuvonralimab (QL1706), a dual-targeting immunotherapy (anti-PD-1/CTLA-4), in patients with intermediate trophoblastic tumors (ITT).
The main questions it aims to answer are:
Does QL1706 improve complete response (CR) rates (primary endpoint) and survival outcomes? What are the safety profiles of QL1706 in ITT, including immune-related adverse events? Participants will receive QL1706 (5 mg/kg IV, Q3W) ± chemotherapy (FAEV/EMA/EP/EMA/CO/TP-TE). They will also receive Maintenance therapy post-hCG normalization. Efficacy is assessed via serial β-hCG tests, imaging (every 9-12 weeks), and biomarker analysis.
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 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Females aged 18-70 years. Histologically confirmed placental site trophoblastic tumor (PSTT) or epitheloid trophoblastic tumor (ETT)
- •For Cohort A:
- •Stage IV disease (treatment-naïve）, recurrent, or chemotherapy-resistant disease
- •For Cohort B:
- •Stage I-III disease requiring adjuvant chemotherapy post-biopsy/surgery, meeting ≥1 of: Abnormal β-hCG 2 weeks post-surgery; Incomplete resection; High-risk features includes: Interval from last pregnancy ≥48 months; Deep myometrial invasion; Mitotic count >5/HPF; Tumor necrosis.
- •ECOG score 0-
- •Signed informed consent.
- •Organ Function Requirements:
- •Hematologic:
- •WBC ≥3.0×10⁹/L ANC ≥1.5×10⁹/L Platelets ≥80×10⁹/L Hemoglobin ≥8.0 g/dL Creatinine ≤1.5×ULN Total bilirubin ≤1.5×ULN (or direct bilirubin ≤ULN if total bilirubin >1.5×ULN) AST/ALT ≤2.5×ULN INR/PT/aPTT ≤1.5×ULN (or within therapeutic range if on anticoagulants).
排除标准
- •Life expectancy <3 months. Non-gestational trophoblastic tumors. Active malignancy (except if cured ≥3 years prior). Prior immune checkpoint therapy (anti-PD-1/L1, CTLA-4, ICOS, CD40, etc.) or cell-based immunotherapies.
- •Active autoimmune disease requiring systemic treatment (past 2 years). Exceptions: Hormone replacement (e.g., thyroxine), physiologic corticosteroids (≤10 mg/day prednisone equivalent).
- •Active inflammatory bowel disease (e.g., Crohn's, ulcerative colitis). Systemic corticosteroids (>10 mg/day prednisone equivalent) within 14 days. Allowed: Topical/inhaled steroids, prophylactic steroids for contrast allergy.
- •Active hepatitis:
- •HBV DNA >1,000 IU/mL (unless on stable antiviral therapy with DNA <1,000 IU/mL).
- •HCV RNA-positive (unless cured). Active tuberculosis (screening required if suspected). Uncontrolled severe infection (e.g., sepsis, pneumonia requiring hospitalization).
- •Cardiovascular disease: NYHA Class III/IV heart failure or LVEF <50%. Uncontrolled hypertension (≥140/90 mmHg despite treatment). Unstable angina, myocardial ischemia, or arterial thromboembolism (≤6 months).
- •Interstitial lung disease (history or active). Malabsorption syndromes (e.g., chronic diarrhea, bowel obstruction) or GI perforation/fistula (≤6 months).
- •Psychiatric/social conditions impairing consent or compliance. Allogeneic transplant history. Live vaccines ≤30 days prior to QL1706 or planned during study. Hypersensitivity to monoclonal antibodies or protocol-specified chemotherapies. Pregnancy/lactation. Other conditions deemed to compromise patient safety or study integrity.
研究组 & 干预措施
QL1706±chemo
Cohort A: QL1706: 5 mg/kg, intravenous (IV) infusion, every 3 weeks (Q3W), administered on Day 1 (D1).Chemotherapy Options: FAEV, EMA/EP, EMA/CO, or TP/TE.
Cohort B: QL1706: 5 mg/kg, IV infusion, Q3W (D1).
干预措施: QL1706 (Drug)
QL1706±chemo
Cohort A: QL1706: 5 mg/kg, intravenous (IV) infusion, every 3 weeks (Q3W), administered on Day 1 (D1).Chemotherapy Options: FAEV, EMA/EP, EMA/CO, or TP/TE.
Cohort B: QL1706: 5 mg/kg, IV infusion, Q3W (D1).
干预措施: Chemotherapy (Drug)
结局指标
主要结局
Complete Response (CR) Rate
时间窗: up to one year
Percentage of patients achieving CR, as defined by normalization of serum hCG (≤5 IU/L for ≥4 weeks)
次要结局
- Objective Response Rate (ORR)(up to one year)
- Disease Control Rate (DCR)(up to one year)
- Rate of Progression-Free Survival (PFS)(up to one year)
- Rate of Overall Survival (OS)(up to one year)
- Concentration of anti-Müllerian hormone (AMH) to assess ovarian function(up to one year)
- Number of Participants with treatment-related Adverse Events [Safety and Tolerability](up to one year)
- Quality of life of cancer patients by questionnaire(up to one year)
- Cancer specific rehabilitation by questionnaire(up to one year)
- Reproductive concerns after cancer by scale(up to one year)
研究者
xiang yang
Professor
Peking Union Medical College Hospital