A Prospective, Open-label, Multicenter Phase II Clinical Study of Iparomlimab and Tuvonralimab (QL1706) Combined With Standard Chemotherapy or Combined With Intraperitoneal Perfusion Chemotherapy and Olaparib as Neoadjuvant Therapy for Advanced Ovarian Cancer
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- AEs
研究概览
简要总结
This study is a prospective, open-label, multicenter Phase II clinical trial, planning to enroll 50 patients with advanced ovarian cancer. Enrolled participants will be assigned to 2 cohorts based on ECOG performance status and genetic mutation status:
Cohort 1: ECOG PS 0 or 1, all-comers population, regardless of BRCA or HRD test results. Treatment: iparomlimab and tuvonralimab (5 mg/kg, Q3W, D1) + paclitaxel (175 mg/m², Q3W, D1) + carboplatin (AUC 5-6, Q3W, D1)/cisplatin (75 mg/m², Q3W, D1). Planned enrollment: 30 patients.
Cohort 2: ECOG PS 2, BRCA1/2 mutation or HRD positive. Treatment: iparomlimab and tuvonralimab (5 mg/kg, Q3W, D1) + olaparib (300 mg, for 2-3 cycles, bid) + intraperitoneal perfusion (cisplatin, 75 mg/m², Q3W, D1). Planned enrollment: 20 patients.
Neoadjuvant therapy will be administered for 3 cycles, followed by patient status assessment. Patients with CR/PR/SD will be allowed to undergo surgery, while PD patients will have subsequent treatment strategies determined by the investigator.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Participants voluntarily join this study, sign the informed consent form, and strictly comply with the protocol requirements;
- •Female patients aged between 18 and 75 years;
- •Patients who have undergone open surgery, laparoscopic surgery, or core needle aspiration biopsy, and have been histopathologically confirmed as having epithelial ovarian cancer (high-grade serous adenocarcinoma, endometrioid adenocarcinoma), peritoneal cancer, or fallopian tube cancer, FIGO 2018 Stage III-IV;
- •Meet the indications for neoadjuvant chemotherapy in ovarian cancer: ① Preoperative assessment by gynecologic oncologists (with multidisciplinary consultation when necessary) indicates low likelihood of achieving R0 resection with primary debulking surgery; ② Physical condition unable to tolerate PDS, unsuitable for immediate surgery (e.g., high perioperative risk, advanced age, medical comorbidities, etc.); ③ No prior systemic anti-tumor treatment for ovarian cancer (including but not limited to radiotherapy, chemotherapy, surgery, targeted therapy, and immunotherapy); Note: Lymph node dissection or biopsy performed for clinical staging purposes after obtaining histopathology via needle biopsy, laparoscopic exploration, or other methods is permitted;
- •Accept BRCA1/2 genetic mutation or HRD testing;
- •Presence of at least one measurable lesion according to RECIST 1.1 criteria;
- •Expected survival time ≥12 weeks;
- •ECOG score 0-1 (for Cohort 1), ECOG score 2 (for Cohort 2);
- •Adequate organ function, including:
- •Bone marrow function: Absolute neutrophil count ≥1,500/μL; Platelets ≥100,000/μL; Hemoglobin ≥10 g/dL Hepatic function: Total bilirubin ≤1.5× upper limit of normal (ULN) or direct bilirubin ≤1.0× ULN; AST and ALT ≤2.5× ULN; Must be ≤5× ULN when liver metastases are present Renal function: Serum creatinine ≤1.5× ULN, or creatinine clearance ≥60 mL/min (calculated using the Cockcroft-Gault formula);
- •Participants of childbearing potential must use appropriate contraceptive methods during the study period and for 120 days after study completion, have a negative serum pregnancy test within 7 days before study enrollment, and must be non-lactating participants.
排除标准
- •Non-epithelial origin ovarian cancer, fallopian tube cancer, or primary peritoneal cancer (e.g., germ cell tumors); ovarian tumors of low malignant potential (e.g., borderline tumors);
- •Concurrent use of other cancer neoadjuvant therapies during this study, including but not limited to chemotherapy, radiotherapy, immunotherapy, microbial therapy, traditional Chinese medicine, and other experimental therapies;
- •Hypersensitivity to the active or inactive ingredients of the investigational drug or drugs with similar structure to the investigational drug;
- •Inability to swallow oral medications and any gastrointestinal disorders that may interfere with the absorption and metabolism of study drugs (for Cohort 2);
- •Prior treatment with known or suspected poly (ADP-ribose) polymerase (PARP) inhibitors (for Cohort 2);
- •Presence of symptomatic or uncontrolled brain metastases requiring concurrent treatment;
- •Active or potentially recurrent autoimmune disease; exceptions include: vitiligo, alopecia, psoriasis, or eczema not requiring systemic treatment; hypothyroidism caused by autoimmune thyroiditis requiring only stable dose hormone replacement therapy; Type 1 diabetes requiring only stable dose insulin replacement therapy;
- •Major surgery within 3 weeks before study initiation, or incomplete recovery from surgery;
- •History of organ transplantation, autologous/allogeneic stem cell transplantation;
- •Known or self-reported human immunodeficiency virus (HIV) infection;
- •HBV-DNA positive, HCV-DNA positive (copy number >10³);
- •Prior treatment with immune checkpoint inhibitors (e.g., anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, etc.), immune checkpoint agonists (e.g., antibodies targeting ICOS, CD40, CD137, GITR, OX40, etc.), immune cell therapy, or any other treatments targeting tumor immune mechanisms;
- •Live vaccine administered within 4 weeks before first dose, or planned live vaccine administration during the study period;
- •History of other malignancies within the past 3 years, except for cutaneous squamous cell carcinoma, basal cell carcinoma, ductal carcinoma in situ of the breast, or cervical carcinoma in situ;
- •Prior or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML);
- •Patients who received platelet or red blood cell transfusions within 4 weeks before initiation of study drug treatment;
- •Pregnant, lactating, or patients planning to become pregnant during study treatment;
- •Patients deemed unsuitable for participation in this study by the investigator.
研究组 & 干预措施
Cohort 2：QL1706+olaparib+intraperitoneal perfusion
Cohort 2: ECOG PS 2, BRCA1/2 mutation or HRD positive. Treatment: iparomlimab and tuvonralimab (5 mg/kg, Q3W, D1) + olaparib (300 mg, for 2-3 cycles, bid) + intraperitoneal perfusion (cisplatin, 75 mg/m², Q3W, D1). Planned enrollment: 20 patients.
干预措施: Olaparib (Drug)
Cohort 1：QL1706+paclitaxel +carboplatin /cisplatin
Cohort 1: ECOG PS 0 or 1, all-comers population, regardless of BRCA or HRD test results. Treatment: iparomlimab and tuvonralimab (5 mg/kg, Q3W, D1) + paclitaxel (175 mg/m², Q3W, D1) + carboplatin (AUC 5-6, Q3W, D1)/cisplatin (75 mg/m², Q3W, D1). Planned enrollment: 30 patients.
干预措施: paclitaxel (Drug)
Cohort 1：QL1706+paclitaxel +carboplatin /cisplatin
Cohort 1: ECOG PS 0 or 1, all-comers population, regardless of BRCA or HRD test results. Treatment: iparomlimab and tuvonralimab (5 mg/kg, Q3W, D1) + paclitaxel (175 mg/m², Q3W, D1) + carboplatin (AUC 5-6, Q3W, D1)/cisplatin (75 mg/m², Q3W, D1). Planned enrollment: 30 patients.
干预措施: carboplatin (Drug)
Cohort 1：QL1706+paclitaxel +carboplatin /cisplatin
Cohort 1: ECOG PS 0 or 1, all-comers population, regardless of BRCA or HRD test results. Treatment: iparomlimab and tuvonralimab (5 mg/kg, Q3W, D1) + paclitaxel (175 mg/m², Q3W, D1) + carboplatin (AUC 5-6, Q3W, D1)/cisplatin (75 mg/m², Q3W, D1). Planned enrollment: 30 patients.
干预措施: Iparomlimab and Tuvonralimab (QL1706)Injection (Drug)
Cohort 1：QL1706+paclitaxel +carboplatin /cisplatin
Cohort 1: ECOG PS 0 or 1, all-comers population, regardless of BRCA or HRD test results. Treatment: iparomlimab and tuvonralimab (5 mg/kg, Q3W, D1) + paclitaxel (175 mg/m², Q3W, D1) + carboplatin (AUC 5-6, Q3W, D1)/cisplatin (75 mg/m², Q3W, D1). Planned enrollment: 30 patients.
干预措施: Cisplatin (Drug)
Cohort 2：QL1706+olaparib+intraperitoneal perfusion
Cohort 2: ECOG PS 2, BRCA1/2 mutation or HRD positive. Treatment: iparomlimab and tuvonralimab (5 mg/kg, Q3W, D1) + olaparib (300 mg, for 2-3 cycles, bid) + intraperitoneal perfusion (cisplatin, 75 mg/m², Q3W, D1). Planned enrollment: 20 patients.
干预措施: Iparomlimab and Tuvonralimab (QL1706)Injection (Drug)
Cohort 2：QL1706+olaparib+intraperitoneal perfusion
Cohort 2: ECOG PS 2, BRCA1/2 mutation or HRD positive. Treatment: iparomlimab and tuvonralimab (5 mg/kg, Q3W, D1) + olaparib (300 mg, for 2-3 cycles, bid) + intraperitoneal perfusion (cisplatin, 75 mg/m², Q3W, D1). Planned enrollment: 20 patients.
干预措施: Cisplatin (Drug)
结局指标
主要结局
AEs
时间窗: From enrollment to the end of treatment at 9 weeks
Incidence and severity of AEs and TEAEs, vital signs, and clinically significant abnormal laboratory findings during the study period
次要结局
- ORR(From enrollment to the end of treatment at 9 weeks)
- R0 Resection Rate(Periprocedural)
- DCR(From enrollment to the end of treatment at 9 weeks)
- 12month-OS(From enrollment to the end of treatment at 12 month)
- 24month-OS(From enrollment to the end of treatment at 24 month)
- OS(From enrollment to the end of treatment at 36 month)
- 12month-PFS(From enrollment to the end of treatment at 12 month)
- PFS(From enrollment to the end of treatment at 24 month)
研究者
Xiaoxiang Chen
Department Director
Jiangsu Cancer Institute & Hospital