A Single-arm, Multicenter Phase II Clinical Study of QL1706 Plus Chemotherapy as Neoadjuvant Therapy for Locally Advanced Cervical Cance
概览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Affiliated Cancer Hospital & Institute of Guangzhou Medical University
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Pathological complete response (pCR)
概览
简要总结
Cervical cancer ranks as the second most common malignancy of the female genital tract. According to the World Health Organization, there are 530,000 new cases and approximately 250,000 cervical-cancer-related deaths worldwide each year, with 80% of these deaths occurring in women from developing countries. Early-stage disease can be managed surgically, whereas advanced or recurrent cervical cancer is treated with individualized multimodal therapy; nevertheless, the optimal management of locally advanced cervical cancer (FIGO 2018 stage IB3-IIA2) remains controversial. Chemoradiation is standard, but neoadjuvant chemotherapy followed by radical surgery after tumor down-staging is also used. More than 90% of cervical cancers are driven by persistent infection with high-risk human papillomavirus (HPV), which evades host immunity in part by up-regulating PD-L1 on tumor cells. Published series report PD-L1 positivity in 34.4-96% of cervical cancers, with even higher rates in squamous-cell histology, providing a rationale for PD-1/PD-L1 blockade. QL1706, a novel bispecific immunotherapeutic agent, has recently been approved as monotherapy for second-line treatment of advanced cervical cancer.QL1706, developed by Qilu Pharmaceutical using the proprietary MabPair™ platform, is the first bispecific antibody simultaneously targeting PD-1 and CTLA-4, showing synergistic anti-tumor activity and favorable tolerability.Unlike previous phase II/III trials of PD-1 monotherapy, this study does not restrict enrolment to patients with PD-L1-positive tumors, so QL1706 is expected to confer benefit in the second-line management of recurrent or metastatic cervical cancer. Therefore, investigating QL1706-based combination regimens as neoadjuvant treatment for treatment-naïve disease is also highly relevant and may improve outcomes in women with locally advanced cervical cancer.
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
- •(1) Has given written informed consent (or consent provided by an immediate family member if the subject is unable to do so) after full explanation of the study.
- •(2) Female, aged ≥ 18 and ≤ 70 years on the date of informed-consent signature. (3) Histologically confirmed cervical cancer: A. Squamous-cell carcinoma, adenocarcinoma, or adenosquamous carcinoma; B. Previously untreated-no prior anti-cancer therapy for cervical cancer; C. FIGO 2018 stage IB3 or IIA2; D. Stage IIICr without involvement of the lower third of the vagina and without parametrial infiltration.
- •(4) At least one measurable lesion by CT or MRI per RECIST 1.
- •Note: Lesions situated in a prior radiation field or previously treated by local-regional therapy must be classified as non-target lesions unless clear progression is documented or tumor viability is confirmed by biopsy, and no other measurable lesion exists; in that case the lesion may serve as a target lesion.
- •(5) Archival tumor tissue obtained within 5 years before enrollment OR a freshly obtained biopsy (≈ 7 unstained FFPE slides, minimum 5; preference for recent sample).
- •The biopsied lesion must not be selected as a RECIST 1.1 target lesion unless no other site is suitable and the biopsy was performed outside the screening period. If a subject cannot provide the required slides and the investigator judges re-biopsy to be unsafe, the number of slides may be reduced at the investigator's discretion.
- •(6) Eastern Cooperative Oncology Group (ECOG) performance status 0 or
- •(7) Life expectancy ≥ 12 weeks. (8) Adequate function of major organs documented within 14 days before randomisation (no transfusion, albumin, recombinant human thrombopoietin or colony-stimulating factors allowed during this period): Haematology Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L Platelets ≥100 × 10⁹/L Haemoglobin ≥90 g/L Hepatic Total bilirubin ≤1.5 × upper limit of normal (ULN) ALT and AST ≤2.5 × ULN (≤5 × ULN if liver metastases present) Serum albumin ≥30 g/L Renal Serum creatinine ≤1.5 × ULN; OR if \>1.5 × ULN, calculated creatinine clearance ≥60 mL/min (Cockcroft-Gault) Coagulation APTT ≤1.5 × ULN PT/INR ≤1.5 × ULN Cardiac Left-ventricular ejection fraction (LVEF) ≥50% Urinalysis Dipstick proteinuria \<2+ If ≥2+, 24-hour urine protein must be \<1.0 g to permit entry (9) Women of child-bearing potential must use a highly effective contraceptive method from informed-consent signature until 180 days after the last study-dose administration and must not be pregnant or lactating.
排除标准
- •(1) Prior exposure to any immunotherapy, including immune-checkpoint inhibitory antibodies (e.g., anti-PD-1, anti-PD-L1, anti-CTLA-4), immune-checkpoint agonistic antibodies (e.g., anti-ICOS, CD40, CD137, GITR, OX40), or cellular immunotherapy.
- •(2) Systemic or severe infection requiring intravenous antibiotics for \>7 days within 2 weeks before enrolment, or unexplained fever \>38.5 °C detected during screening or within 2 weeks prior to enrolment (fever judged by the investigator to be tumour-related is permitted).
- •(3) Systemic corticosteroids (\>10 mg/day prednisone or equivalent) or other immunosuppressive agents (e.g., cyclophosphamide, azathioprine, methotrexate, thalidomide, TNF-α inhibitors) for any indication within 2 weeks before enrolment. Topical, nasal or inhaled corticosteroids are allowed; systemic steroids given solely for prophylaxis of contrast allergy are also permitted.
- •(4) Treatment with immunomodulatory agents such as thymosin, lentinan, interferon or interleukins within 2 weeks before enrolment.
- •(5) Use within 2 weeks before enrolment of aspirin (\>325 mg/day), clopidogrel (\>75 mg/day), dipyridamole, ticlopidine, cilostazol, or any therapeutic-dose anticoagulant other than low-molecular-weight heparin.
- •(6) Use of modern Chinese herbal preparations approved by NMPA for anti-cancer therapy within 2 weeks before enrolment.
- •(7) Major surgery, open biopsy or significant traumatic injury within 4 weeks before enrolment; or planned elective major surgery during the study. Local invasive procedures (e.g., core biopsy) within 1 week before enrolment are excluded, except for vascular-access device placement.
- •(8) Anti-cancer therapy (chemotherapy, endocrine therapy, targeted therapy, biological therapy, trans-arterial chemo-embolisation, etc.) within 4 weeks before enrolment.
- •(9) Symptomatic CNS metastases, leptomeningeal disease or spinal-cord compression at baseline. Asymptomatic subjects with stable CNS disease who have completed any prior CNS-directed therapy ≥2 weeks earlier and have been off corticosteroids and anti-convulsants for ≥2 weeks may be enrolled.
- •(10) Clinically significant hydronephrosis that cannot be relieved by nephrostomy or ureteral stenting.
结局指标
主要结局
Pathological complete response (pCR)
时间窗: 2 years
Pathological complete response (pCR) is defined as the absence of residual malignant tumor cells in the resected specimen.
次要结局
- Objective response rate (ORR)(2 years)
- Disease-free survival (DFS)(2 years)
- 2-year disease-free survival rate (2-year DFS rate)(2 years)
研究者
Lipai Chen
Chief physician
Affiliated Cancer Hospital & Institute of Guangzhou Medical University