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
This is a prospective, multicenter, phase II study designed to evaluate the efficacy and safety of disitamab vedotin combined with platinum plus bevacizumab as first-line therapy for HER2-expressing, HRD-negative high-risk ovarian cancer. Forty-three patients with pathologically confirmed HRD-negative high-risk ovarian cancer will be enrolled. After enrollment, patients will receive disitamab vedotin plus platinum and bevacizumab as first-line and maintenance treatment. First-line phase: Carboplatin AUC 5 intravenously on Day 1 every 21 days over 1 h ,Bevacizumab 7.5-15 mg/kg intravenously on Day 1 every 21 days over 30-90 min. Maintenance phase: Patients who achieve response (CR or PR) will continue disitamab vedotin monotherapy plus bevacizumab (investigator decides whether to continue disitamab vedotin and for how long). Maintenance duration: bevacizumab until disease progression or up to 22 cycles; disitamab vedotin up to 6 months (8 cycles).
• 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
‣ a) 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.