Biomarker-driven Targeted Therapy in Patients With Recurrent Platinum-resistant Epithelial Ovarian Cancer

Inclusion Criteria:

1. Voluntary participation and signing of informed consent
2. Age ≥ 18 years;
3. the Eastern United States cancer cooperation group (ECoG) score 0-1;
4. Platinum-resistant recurrent ovarian cancer (PROC): the patient was diagnosed with platinum-resistant recurrence for the first time. PROC refers to the disease progression that occurred \< 6 months after the last dose of platinum-based chemotherapy. Imaging-based evaluation for the latest recurrence/progression before enrollment was required;
5. Malignant epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer confirmed by histology or cytology, including high-grade serous cancer, low-grade serous cancer, endometrioid cancer, clear cell cancer, mucinous cancer, and carcinosarcoma;
6. Biomarker detection and tumor sample collection meet the following standards:

   * Patients must provide archived tumor tissue samples (formalin-fixed, paraffin-embedded tumor tissue blocks \[preferred\], or at least 10 unstained tissue sections), except for patients with serous carcinoma, endometrioid carcinoma, clear cell carcinoma and gBRCAm
   * If the patient has been tested for BRCA1 / 2 gene in the past, only the corresponding test report needs to be provided
7. Sufficient organ functions, which is defined as:

   * neutrophil absolute value (ANC) ≥ 1.5 × 109/L
   * platelet count (PLT) ≥ 75 × 10\*9/L
   * hemoglobin ≥ 9 g / dl
   * serum creatinine CR \< 1.5 × Upper normal value (ULN)
   * total serum bilirubin ≤ 1.5 × Upper normal range (ULN)
   * both aspartate aminotransferase and alanine aminotransferase ≤ 3 × ULN
   * coagulation function: international normalized ratio (INR) ≤ 1.5; Activated partial prothrombin time (APTT) ≤ 1.5 × ULN
8. Patients must have lesions that can be measured according to RECIST v1.1 standard;
9. Participants were allowed to have previously VEGF / VEGFR inhibitors treatment;
10. Participants were allowed to have previously PARP inhibitors treatment. However, for treatment arm 1 (arm1), the exposure time of PARP inhibitors should ≥ 12 months after first-line chemotherapy or ≥ 6 months after second-line and above chemotherapy;
11. Life expectancy ≥ 3 months;

Exclusion Criteria:

1. The exclusion criteria of bevacizumab were clinically significant cardiovascular and cerebrovascular diseases, history of abdominal fistula or gastrointestinal perforation, acute intestinal obstruction or sub obstruction, and active bleeding;
2. Uncontrolled hypertension (systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg) or clinically significant (active) cardiovascular disease: cerebrovascular accident (CVA) / stroke ≤ 6 months from the treatment of the first clinical study; Myocardial infarction ≤ 6 months from the first clinical study treatment; Unstable angina pectoris; Congestive heart failure (CHF) of grade II or above in the cardiac function classification standard of the New York Heart Association (NYHA); Serious arrhythmias requiring treatment;
3. Previous medical history showed newly discovered thrombotic diseases within 6 months before or during the screening period; Patients with severe wound nonunion, ulcer, or fracture;
4. Major surgery within 30 days before the first administration of study treatment; Patients expected to have invasive surgery during treatment;
5. Patients with other malignant tumors;
6. Patients who have previously received anti-programmed cell death protein-1 (anti-PD-1), anti-programmed death ligand-1 (anti-PD-L1) or anti-PD-L2 drugs, or another drug treatment for T cell inhibitory receptors (e.g., cytotoxic T lymphocyte-associated antigen-4 \[CTLA-4\], OX-40, CD137 \[tumor necrosis factor receptor superfamily member 9 (tnfrsf9)\];
7. Active autoimmune diseases requiring systemic treatment in the past 2 years;
8. Any case requiring systemic treatment with corticosteroids (prednisone or equivalent \> 10 mg/day) or other immunosuppressive drugs ≤ 14 days before the first administration of the study drug;
9. Known history of human immunodeficiency virus (HIV) infection;
10. Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers (HBV DNA \> 500 IU / ml) or active HCV carriers with detectable HCV RNA; Note: inactive hepatitis B surface antigen (HBsAg) carriers and treated and stable hepatitis B patients (HBV DNA \< 500 IU / ml) can be included in the group;
11. History of interstitial lung disease, noninfectious pneumonia, or uncontrolled diseases, including pulmonary fibrosis, acute lung disease, etc;
12. Previous heterologous stem cell transplantation or organ transplantation;
13. Peripheral neuropathy ≥ grade 2;
14. Foods or drugs that are expected to use CYP3A4 strong inducers or strong inhibitors within 28 days before the use of the study drug;
15. Participate in another clinical study at the same time, unless it is an observational (non-intervention) clinical study or is in the follow-up period of intervention study;
16. Women of childbearing age who are unwilling or unable to use effective methods for contraception during the whole treatment period of this trial and within 6 months after the last administration of the study drug \[women of childbearing age include: any women who have had menarche and have not undergone successful artificial sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), or premenopausal\], pregnant or lactating women.
17. Other conditions judged by the researcher that do not meet the enrollment requirements.