Ovarian cancer is one of the most common gynecologic malignancies, with considerable histologic heterogeneity; more than 90 % of cases are epithelial ovarian cancers. Because no reliable tools exist for early detection, approximately 70 % of patients are diagnosed at an advanced stage and have poor prognosis, and \>70 % experience relapse within 3 years of initial treatment. The standard first-line strategy combines cytoreductive surgery, platinum-based chemotherapy, and maintenance with PARP inhibitors. Management of recurrent disease remains one of the most challenging problems in clinical oncology.
Bevacizumab, a recombinant humanized anti-VEGF monoclonal antibody that blocks endothelial proliferation and neovascularization, is the prototypic angiogenesis inhibitor used in ovarian cancer. However, randomized trials have demonstrated only progression-free survival (PFS) benefit, with no overall survival (OS) advantage. Pre-clinical data suggest that immunotherapy and anti-angiogenic agents can exert synergistic anti-tumor activity, yet clinical efforts combining bevacizumab with immune-checkpoint inhibitors in recurrent ovarian cancer-whether added to platinum-based chemotherapy, used as maintenance, or evaluated in chemotherapy-free regimens-have thus far been unsuccessful (except in clear-cell histology).
Anlotinib is a novel oral multi-target tyrosine-kinase inhibitor that blocks VEGFR-2/3, FGFR 1-4, PDGFR-α/β, c-KIT, and RET, thereby potently suppressing angiogenesis. Accumulating evidence indicates that anlotinib plus chemotherapy is more effective than chemotherapy alone in advanced or recurrent ovarian cancer, with a manageable safety profile, showing encouraging efficacy and tolerability.
Because conventional approaches for recurrent ovarian cancer are limited-particularly once platinum resistance develops-new therapeutic strategies are urgently needed. The best-characterized immune-checkpoint molecules are CTLA-4 and the PD-1/PD-L1 axis. Combined blockade of CTLA-4 and PD-1 has yielded impressive activity in several tumor types. Although single-agent checkpoint inhibitors produce modest response rates in recurrent ovarian cancer, preliminary data suggest that dual inhibition with anti-CTLA-4 plus anti-PD-1 antibodies may enhance therapeutic responses.QL1706 is a novel dual-target immunotherapeutic agent that has been approved for second-line monotherapy in 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.The treatment of recurrent ovarian cancer remains a formidable challenge; therefore, proactive exploration of diverse combination regimens is essential to achieve optimal therapeutic efficacy and maximize survival benefit for patients.
1.Capable of understanding and voluntarily signing the written Informed Consent Form (ICF); the ICF must be signed before any study-specific procedures are performed.
Platinum-sensitive relapse (recurrence ≥ 6 months after completion of the last platinum-based therapy).
Platinum-resistant relapse (recurrence < 6 months after completion of the last platinum-based therapy or progression while on PARP-inhibitor maintenance).
1.Non-epithelial ovarian malignancies (e.g., carcinosarcoma, sex-cord stromal tumors).
MI, unstable angina, pulmonary embolism, aortic dissection, DVT, arterial thrombo-embolism within 6 months
NYHA class ≥ II heart failure
Serious arrhythmia requiring chronic therapy (stable-rate asymptomatic atrial fibrillation allowed)
Parallel
QL1706 plus chemotherapy and anlotinib regimen
DrugQL1706 (5 mg/kg) IV d1, q3w Pegylated liposomal doxorubicin hydrochloride (30 mg/m²) IV d1, q3w Carboplatin (AUC = 5) IV d1, q3w -OR- cisplatin (75 mg/m²) IV d1, q3w Anlotinib: 8 mg PO qd d1-14, q3w Administer for 6 cycles.
Objective response rate (ORR)
The ratio of patients who are evaluated as CR or PR
PFS
PFS: defined as the time from the date of first dose to the first documented progressive disease (PD) or death from any cause, whichever occurs first, within the tumor-assessment follow-up period.
DCR
DCR: the proportion of patients with best overall response of complete response (CR), partial response (PR), or stable disease (SD) for ≥4 weeks.
OS
OS: defined as the time from the date of first dose to death from any cause (for patients lost to follow-up before death, the date of last known contact is conventionally used as the date of death).
DOR
DOR: In patients who achieve an objective response, DOR is defined as the time from the first documented complete response (CR) or partial response (PR) (whichever occurs first) to the date of progressive disease (PD) or death from any cause (whichever occurs first).
TTR
TTR (Time to Response): For patients who achieve an objective response, TTR is defined as the time from the date of first dose to the first documented complete response (CR) or partial response (PR), whichever occurs first.
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