Trastuzumab Rezetecan and Carboplatin ± Bevacizumab Versus Investigator's Choice Chemotherapy in Patients With Platinum-sensitive Recurrent Ovarian Cancer

Trastuzumab Rezetecan and Carboplatin With or Without Bevacizumab Versus Investigator's Choice Chemotherapy in Patients With Platinum-sensitive Recurrent Ovarian Cancer: an Open-label, Multicenter, Randomized Controlled Phase II Study

This study is a randomized, open-label, controlled phase II clinical trial.

It is planned to enroll 176 subjects with platinum-sensitive recurrent epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer previously treated with Poly (ADP-ribose) polymerase inhibitors (PARPi).

Subjects will be randomly assigned in a 1:1 ratio to receive either the experimental treatment group (trastuzumab Rezetecan + carboplatin ± bevacizumab) or the control treatment group (investigator's choice chemotherapy ± bevacizumab).

Inclusion Criteria:

1. Subjects voluntarily participate in this study, sign the informed consent form, and have good compliance.
2. Aged 18 to 75 years.
3. Histologically confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.
4. Have received 1-3 prior lines of platinum-based chemotherapy and have experienced disease progression or recurrence ≥6 months after the last platinum-based treatment (platinum-sensitive relapse).
5. Must have received prior treatment with a PARP inhibitor.
6. Able to provide sufficient fresh or archival tumor tissue specimens for detection of HER2 expression levels.
7. Have at least one measurable lesion per RECIST v1.1.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
9. Expected survival of more than 3 months.
10. Adequate major organ function.
11. Subjects of childbearing potential must use at least one medically approved contraceptive measure (e.g., intrauterine device, contraceptive pill, or condom) during the study treatment period and for 180 days after the end of study treatment; must have a negative serum/urine HCG test before the first dose; and must not be breastfeeding.

Exclusion Criteria:

1. Ovarian cancer with pathological types of clear cell carcinoma, low-grade serous adenocarcinoma, or mucinous adenocarcinoma.
2. Known allergy to any component of trastuzumab rezetecan; known allergy to carboplatin.
3. Prior treatment with anti-HER2 therapy, an antibody-drug conjugate (ADC) containing a topoisomerase I inhibitor, or a topoisomerase I inhibitor alone.
4. Untreated or active central nervous system (CNS) metastases.
5. Prior history of interstitial pneumonia/interstitial lung disease or non-infectious pneumonitis (e.g., radiation pneumonitis) that required steroid treatment; current or suspected interstitial pneumonia/interstitial lung disease, non-infectious pneumonitis, or other active pneumonitis.
6. Active ulcer, intestinal perforation, or intestinal obstruction.
7. Known hereditary or acquired bleeding disorders (e.g., coagulation dysfunction, hemophilia) or thrombotic tendency.
8. Toxicity from prior anti-tumor therapy that has not recovered to ≤ Grade 1 per NCI-CTCAE v6.0.
9. Arterial/venous thrombotic events (including but not limited to cerebrovascular accident, deep vein thrombosis, and pulmonary embolism) within 6 months before the first dose; however, if muscular venous thrombosis or catheter-related thrombosis associated with an infusion port is present before the first dose and the investigator deems it to be without risk, the subject may be enrolled.
10. Hypertension not well controlled with antihypertensive medication (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥90 mmHg).
11. Uncontrolled or severe cardiovascular disease, such as unstable angina, symptomatic congestive heart failure (NYHA class II-IV), myocardial infarction within 6 months before the first dose, or unstable angina or unstable arrhythmia within 1 month before the first dose.
12. Prior surgery, radical radiotherapy, chemotherapy, macromolecular targeted therapy, or anti-tumor immunotherapy with completion (last dose) less than 4 weeks before the first dose; prior small-molecule targeted drugs with last dose less than 5 half-lives or 4 weeks (whichever is shorter) before the first dose; prior palliative radiotherapy or local therapy with completion less than 2 weeks before the first dose.
13. Pleural effusion, pericardial effusion, or ascites that cannot be controlled with appropriate interventions.
14. Severe infection within 1 month before the first dose, including but not limited to infectious complications requiring hospitalization, bacteremia, or severe pneumonia.
15. Concurrent or previous other malignancies, except for cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, papillary thyroid carcinoma, and other malignancies that have been adequately treated and cured for ≥3 years with documented evidence of no recurrence or metastasis.
16. History of immunodeficiency (including HIV-positive test), other acquired or congenital immunodeficiency diseases, or history of organ transplantation; known active hepatitis B (defined as HBsAg-positive with HBV DNA ≥500 IU/mL [or ≥2500 copies/mL if the study site only uses copies/mL, in which case the subject is not eligible]) or active hepatitis C (defined as positive hepatitis C virus antibody [HCV-Ab] and positive HCV-RNA at screening).
17. Any clinical or laboratory abnormality or other reason that, in the investigator's opinion, makes the subject unsuitable for participation in this clinical study.