Disitamab Vedotin Combined With Platinum and Bevacizumab as First-Line and Maintenance Therapy for HER2-Expressing, HRD-Negative High-Risk Ovarian Cancer: A Multicenter, Non-Randomized, Single-Arm Phase II Clinical Study

Exclusion Criteria

• •Non-high-risk histologic sub-types of ovarian carcinoma.
• •CNS metastases and/or carcinomatous meningitis. -
• •Requirement for parenteral hydration/nutrition OR clinical/radiologic evidence of partial bowel obstruction or perforation.
• •≥ Grade-2 peripheral neuropathy. -
• •Active bleeding or high bleeding-risk conditions (e.g., known coagulopathy, tumour encasing major vessels).
• •Interval between cytoreductive surgery and first bevacizumab dose \< 28 days.
• •Concurrent malignancy or history of another primary malignancy within 5 years (except adequately treated in-situ cervix cancer, basal- or squamous-cell skin cancer).
• •Major surgery within 4 weeks before first study dose and not fully recovered.
• •Symptomatic or medically-requiring large-volume pleural effusion or ascites. - Live-attenuated vaccine within 30 days before first dose or planned during study.
• •Significant arterial/venous thrombo-embolic or cerebro-cardiovascular event within 12 months before screening (e.g., DVT, PE, cerebral infarction, intracranial haemorrhage, MI); asymptomatic calf-muscle DVT not needing intervention or lacunar infarct without sequelae are allowed.
• •Uncontrolled systemic diseases judged by investigator: diabetes, liver cirrhosis Child-Pugh B/C, interstitial pneumonitis, severe COPD, etc.
• •Clinically-relevant cardiovascular disorders:
• •1. PR interval \> 0.24 s or 2nd/3rd-degree AV block.
• •2. Uncontrolled hypertension (SBP \> 150 mmHg or DBP \> 90 mmHg).
• •3. MI, unstable angina or significant arrhythmia \< 6 months before enrolment.
• •4. NYHA class ≥ II congestive heart failure.
• •5. Serious arrhythmia requiring anti-arrhythmic therapy.
• •6. ≥ Stage-II peripheral vascular disease (except transient ischaemia \< 24 h without permanent deficit and no surgery).
• •7. Cerebrovascular accident within 6 months.
• •Severe infection within 4 weeks before first dose (IV antibiotics/antifungals/ antivirals required) or unexplained fever \> 38.5 °C during screening; major surgery within 3 weeks.
• •Active autoimmune or immunodeficiency disorders (e.g., autoimmune hepatitis, interstitial pneumonia, uveitis, RA, IBD, hypophysitis, vasculitis, nephritis). Exceptions: stable hypothyroidism on replacement, type-1 diabetes well controlled with insulin.
• •Autoimmune disease requiring systemic immunosuppressive/immunomodulatory therapy within 2 years before first dose (stable replacement therapy with thyroxine, insulin or physiological corticosteroids permitted).
• •Active or poorly controlled infection, including:
• •1. HIV positive (HIV-1/2 antibody).
• •2. Active hepatitis B (HBsAg positive or HBV DNA \> 2 000 IU/mL with abnormal LFT).
• •3. Active hepatitis C (HCV antibody positive or HCV RNA ≥ 10³ copies/mL with abnormal LFT).
• •4. Active tuberculosis.
• •5. Other uncontrolled infection \> CTCAE v5.0 grade 2.
• •History of other malignancy within 5 years (except adequately treated in-situ cervical cancer or basal/squamous-cell skin cancer). -
• •Concurrent participation in another interventional clinical trial or investigational agent/device within 4 weeks before first dose. -
• •Known hypersensitivity or intolerance to study drugs or their excipients. -
• •History of substance abuse that cannot be abstained from, or any psychiatric disorder that may interfere with compliance.
• •Any other condition that, in the investigator's opinion, could increase risk or preclude safe completion of the protocol.