Ovarian Cancers
Conditions
Keywords
ovarian cancer, ICIs, Neoadjuvant therapy, QL1706, olaparib
Brief summary
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.
Interventions
5 mg/kg, Q3W, D1
DRUGpaclitaxel
175 mg/m², Q3W, D1
DRUGcarboplatin
AUC 5-6, Q3W, D1
DRUGCisplatin
75 mg/m², Q3W, D1
DRUGOlaparib
300 mg, for 2-3 cycles, bid
Sponsors
Jiangsu Cancer Institute & Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AEs | 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 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
China
Contacts
CONTACTXiao Xiang Chen
Outcome results
None listed