Iparomlimab and Tuvonralimab (QL1706) Combined With Standard Chemotherapy or Combined With Intraperitoneal Perfusion Chemotherapy and Olaparib as Neoadjuvant Therapy for Advanced Ovarian Cancer

Korábbi kezelés

• 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;
• 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;
• Major surgery within 3 weeks before study initiation, or incomplete recovery from surgery;
• 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;
• Prior or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML);

Más betegség

• 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);
• Inability to swallow oral medications and any gastrointestinal disorders that may interfere with the absorption and metabolism of study drugs (for Cohort 2);
• 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;
• 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);
• 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;

Laborértékek

• Patients who received platelet or red blood cell transfusions within 4 weeks before initiation of study drug treatment;

Egyéb

• Pregnant, lactating, or patients planning to become pregnant during study treatment;
• Patients deemed unsuitable for participation in this study by the investigator.

• 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.