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

Korábbi kezelés

• 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.
• Clinically-relevant cardiovascular disorders:
  • PR interval \> 0.24 s or 2nd/3rd-degree AV block.
  • Uncontrolled hypertension (SBP \> 150 mmHg or DBP \> 90 mmHg).
  • MI, unstable angina or significant arrhythmia \< 6 months before enrolment.
  • NYHA class ≥ II congestive heart failure.
  • Serious arrhythmia requiring anti-arrhythmic therapy.
  • ≥ Stage-II peripheral vascular disease (except transient ischaemia \< 24 h without permanent deficit and no surgery).
  • 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.
• Concurrent participation in another interventional clinical trial or investigational agent/device within 4 weeks before first dose. -

Más betegség

• Requirement for parenteral hydration/nutrition OR clinical/radiologic evidence of partial bowel obstruction or perforation.
• Active bleeding or high bleeding-risk conditions (e.g., known coagulopathy, tumour encasing major vessels).
• Uncontrolled systemic diseases judged by investigator: diabetes, liver cirrhosis Child-Pugh B/C, interstitial pneumonitis, severe COPD, etc.
• 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:
  • HIV positive (HIV-1/2 antibody).
  • Active hepatitis B (HBsAg positive or HBV DNA \> 2 000 IU/mL with abnormal LFT).
  • Active hepatitis C (HCV antibody positive or HCV RNA ≥ 10³ copies/mL with abnormal LFT).
  • Active tuberculosis.
  • 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). -
• 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.

Egyéb

• Non-high-risk histologic sub-types of ovarian carcinoma.
• CNS metastases and/or carcinomatous meningitis. -
• ≥ Grade-2 peripheral neuropathy. -

• Voluntary participation with written informed consent.
• Age 18-75 years.
• Expected survival ≥ 12 weeks.
• Histologically/cytologically confirmed advanced ovarian carcinoma (FIGO Stage III-IV).
• HRD-negative status per local assessment.
• High-risk features: macroscopic residual disease after primary cytoreductive surgery for Stage III; prior neoadjuvant chemotherapy; or Stage IV disease.
• ≥ 1 RECIST v1.1 measurable lesion (long-axis ≥ 10 mm by spiral CT or ≥ 15 mm short-axis for lymph nodes).
• HER2 expression documented locally (IHC 1+, 2+, or 3+); archival or fresh tumor tissue (paraffin block or unstained slides) must be available for central confirmation.
• ECOG performance status 0-1.
• Adequate organ function within 14 days before enrolment (no transfusion/haematinics/G-CSF allowed):
  • Haematology
• Hb ≥ 90 g/L
• WBC ≥ 3 × 10⁹/L
• ANC ≥ 1.5 × 10⁹/L
• PLT ≥ 90 × 10⁹/L Biochemistry
• TBIL ≤ 1.5 × ULN b) ALT/AST/ALP ≤ 3 × ULN (≤ 5 × ULN if liver metastases) c) Serum creatinine ≤ 1.5 × ULN or CrCl ≥ 60 mL/min (Cockcroft-Gault)
• Urinalysis: dipstick proteinuria \< 2+ or 24-h urine protein \< 1 g.
• Cardiac function: NYHA class \< III and LVEF ≥ 50 % by echocardiography. -
• Women must be surgically sterile, post-menopausal, or use an approved contraceptive method from screening until 6 months after the last dose; serum pregnancy test negative within 7 days of first dose and not breastfeeding.
• Able and willing to comply with all study and follow-up procedures.