Trastuzumab Rezetecan Plus Bevacizumab in Platinum-Sensitive Recurrent Ovarian Cancer

• Trastuzumab Rezetecan (SHR-A1811) (Drug): Humanized anti-HER2 IgG1 monoclonal antibody conjugated with a topoisomerase I inhibitor payload (SHR169265). Administered IV at 4.8 mg/kg on Day 1 of each 21-day cycle.
• Bevacizumab (Drug): Recombinant humanized anti-VEGF monoclonal antibody. Administered IV at 7.5 mg/kg on Day 1 of each 21-day cycle (dosing interval >30 min after SHR-A1811).
• Platinum-based chemotherapy (Drug): Platinum-based chemotherapy rechallenge administered in Stage 2, selected by the investigator based on patient clinical condition (including but not limited to: Carboplatin + Paclitaxel ± Bevacizumab, Carboplatin + Pegylated Liposomal Doxorubicin ± Bevacizumab, or Carboplatin + Gemcitabine ± Bevacizumab; Cisplatin or Nedaplatin may be substituted if carboplatin is not tolerated).

Primary outcomes

• PFS1 [From the first dose of study treatment up to approximately 36 months.]: Progression-Free Survival 1 (PFS1) as assessed by the investigator based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Defined as the time from the date of the first dose of study treatment to the date of first documented objective tumor progression or death due to any cause, whichever occurs first.

Secondary outcomes

• Objective Response Rate (ORR) [Up to approximately 36 months.]: Defined as the proportion of subjects who achieve a Best Overall Response (BOR) of confirmed Complete Response (CR) or Partial Response (PR) based on RECIST v1.1 criteria.
• Disease Control Rate (DCR) [Up to approximately 36 months.]: Defined as the proportion of subjects who achieve Complete Response (CR), Partial Response (PR), or Stable Disease (SD) based on RECIST v1.1 criteria.
• Progression-Free Survival 2 (PFS2) [Up to approximately 36 months.]: Defined as the time from the date of the first dose of study treatment in Stage 1 to the second documented objective disease progression or death due to any cause, whichever occurs first.
• Overall Survival (OS) [Up to approximately 36 months.]: Defined as the time from the date of the first dose of study treatment to death due to any cause, calculated in the intent-to-treat (ITT) population.
• Safety and Tolerability [From signing the informed consent form up to 30 days after the last dose of study treatment (and up to 90 days after the last dose of bevacizumab).]: Incidence, severity, and causality of adverse events (AEs) and serious adverse events (SAEs) graded according to NCI-CTCAE v5.0 criteria, as well as the proportion of dose interruptions, dose reductions, and treatment discontinuations due to treatment-related toxicities.

Sex: Female, ages: 18 Years to 75 Years

Inclusion Criteria:

1. Voluntarily agree to participate in the study, provide written informed consent, demonstrate good compliance, and be able to cooperate with protocol-required follow-up visits.
2. Female patients aged 18 to 75 years old (inclusive, calculated from the date of signing the informed consent form).
3. Histologically or cytologically confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer (mucinous carcinoma is excluded).
4. Received 1 to 2 prior lines of systemic therapy and must have received prior PARP inhibitor therapy.
5. Partially platinum-sensitive recurrence, defined as disease recurrence occurring ≥6 months but <12 months after the completion of the last platinum-containing therapy:

   * Neoadjuvant and/or adjuvant therapy are combined and counted as 1 line of therapy;
   * Maintenance therapy does not count as a separate line of therapy;
   * Changes in treatment regimens due to reasons other than disease progression (such as intolerable toxicity) are considered part of the same line of therapy and are not counted separately.
6. Confirmed HER2 expression status: IHC 1+, 2+, or 3+.
7. At least one measurable lesion according to RECIST v1.1 criteria (longest diameter ≥10 mm on spiral CT scan, or short axis ≥15 mm for lymph nodes).
8. ECOG performance status (PS) score: 0 to 1..
9. Expected life expectancy ≥12 weeks.
10. Adequate function of vital organs.

Exclusion Criteria:

1. Central nervous system (CNS) metastasis: Untreated or active CNS metastases. Subjects are eligible if CNS metastases have received adequate local therapy (e.g., surgery or radiotherapy), neurological symptoms have returned to baseline (excluding residual signs or symptoms related to CNS treatment), and clinical stability has been maintained for ≥ 4 weeks prior to the first dose.
2. Second primary malignancy, except for the following: adequately treated basal cell carcinoma of the skin, cervical carcinoma in situ, ductal carcinoma in situ of the breast, or papillary thyroid carcinoma; or other malignancies that have been adequately treated with curative intent and have shown no evidence of recurrence or metastasis for >= 2 years prior to the first dose.
3. Uncontrolled pleural effusion or ascites. Subjects are eligible if therapeutic drainage has been performed and clinical stability has been maintained for at least 2 weeks after drainage.
4. Severe pulmonary disease: History of interstitial lung disease (ILD) or non-infectious pneumonitis (such as radiation pneumonitis) requiring systemic corticosteroid therapy; current or suspected ILD, non-infectious pneumonitis, or other active pulmonary inflammation; or significant pulmonary impairment including severe asthma, severe chronic obstructive pulmonary disease (COPD), or restrictive lung disease within 6 months prior to the first dose.
5. Tuberculosis infection: Active pulmonary tuberculosis infection. Subjects who have received adequate and standard anti-tuberculosis therapy and have discontinued anti-tuberculosis treatment for >= 3 months prior to the first dose are eligible.
6. Uncontrolled cardiovascular disease: Poorly controlled or serious cardiovascular disease, including but not limited to unstable angina, symptomatic congestive heart failure (NYHA Class II-IV), acute myocardial infarction within 6 months prior to the first dose, or unstable arrhythmias requiring clinical intervention within 1 month prior to the first dose.
7. High-risk gastrointestinal indications (perforation/fistula): Gastrointestinal perforation, gastrointestinal fistula, tracheoesophageal fistula, urethral fistula, or abdominal abscess occurring within 3 months prior to the first dose, or judged by the investigator to have a high risk of occurrence in the near future. Subjects who have undergone definitive treatments such as artificial stoma or ureteral stent placement and are evaluated by the investigator as clinically stable are eligible.
8. Active infection: Severe infection occurring within 1 month prior to the first dose; any active infection requiring systemic intravenous antimicrobial therapy; or unexplained fever (> 38.5 deg C) from the screening period up to the first dose.
9. Specific prior drug exposure: Prior treatment with antibody-drug conjugates (ADCs) containing a topoisomerase I inhibitor, or prior single-agent topoisomerase I inhibitor therapy (such as irinotecan, topotecan).
10. Drug hypersensitivity: Known hypersensitivity to any active ingredient or excipient of Trastuzumab Rezetecan (SHR-A1811), including the antibody, payload SHR169265, and linker; known hypersensitivity to any component of Bevacizumab, or a history of severe hypersensitivity reactions.
11. Other comprehensive risks: Any clinical condition that, in the opinion of the investigator, may increase the risk to the subject, interfere with the interpretation of study results, or preclude compliance with the study protocol.