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).

Study Overview

• Status: Recruiting
• Conditions: Ovarian Cancer Metastatic; Ovarian Cancer Metastatic Recurrent
• Intervention / Treatment: Drug: RC48+Carboplatin+Bevacizumab

• Study Type: Interventional
• Enrollment (Estimated): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Recruiting
      • Jiangsu Cancer Hospital
      • Contact: Xiaoxiang Chen; Phone Number: 13851647229; Email: cxxxxcyd@gmail.com
    • Nanjing, Jiangsu, China, 210000
      • Not yet recruiting
      • Jiangsu Cancer Hospital
      • Contact: xiang xiao Chen, Chief physician; Phone Number: 025 83283348; Email: cxxxxcyd@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

1. Hb ≥ 90 g/L
2. WBC ≥ 3 × 10⁹/L
3. ANC ≥ 1.5 × 10⁹/L
4. 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.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Arm A

Drug: RC48+Carboplatin+Bevacizumab; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	From enrollment until documented disease progression or death from any cause, whichever occurs first.	From enrollment until 16 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Disease Control Rate (DCR) is defined as the proportion of patients who achieve a Best Overall Response of PR or CR .	up to 24 weeks
Disease Control Rate (DCR)	Disease Control Rate (DCR) is defined as the proportion of patients who achieve a Best Overall Response of PR or CR or SD.	up to 24 weeks
overall survival（OS）	From enrollment until death from any cause.	Up to 5 years
Incidents of Adverse Events	All patients who receive at least one dose of any study drug are included in the safety-analysis set.	30 days after the end of treatment

Collaborators and Investigators

• Sponsor: Jiangsu Cancer Institute & Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: December 16, 2025
• First Submitted That Met QC Criteria: December 29, 2025
• First Posted (Actual): December 31, 2025

Study Record Updates

• Last Update Posted (Actual): December 31, 2025
• Last Update Submitted That Met QC Criteria: December 29, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: HER2-expressing; RC48; HRD-Negative High-Risk Ovarian Cancer
• Other Study ID Numbers: RCVDTYPEC170

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No