The Efficiency of Biomarker-driven Targeted Therapy in Patients With Recurrent Platinum-resistant Epithelial Ovarian Cancer (PROC): An Umbrella Study
Overview
- Phase
- Phase 2
- Intervention
- Pamiparib
- Conditions
- Ovarian Cancer
- Sponsor
- Tongji Hospital
- Enrollment
- 108
- Locations
- 1
- Primary Endpoint
- Objective response rate (ORR)
- Status
- Completed
- Last Updated
- 10 months ago
Overview
Brief Summary
This study is an open-label, multicenter, umbrella study aimed to evaluate the combined, biomarker-driven, targeted treatment efficiency of Pamiparib, Bevacizumab, Tislelizumab, and Nab-paclitaxel in patients with platinum-resistant recurrent ovarian cancer (PROC).
Detailed Description
BRCA1/2 gene status and CD8+ tumor-infiltrating T cell count (CD8 + TILs count) were evaluated as biomarkers using archived tumor tissue samples. Treatment arms were arranged according to pathological diagnosis and biomarker detection results. Arm1 (Biomarkers: BRCA 1/2 mutant): Pamiparib 40mg PO. bid. plus Bevacizumab 7.5mg/kg IV. D1 (q3w.). Arm2 (Biomarkers: BRCA 1/2 wildtype and ≥3 CD8+ TILs count): Tislelizumab 200mg IV. D1 + Bevacizumab 7.5mg/kg IV. D1 + Nab-paclitaxel 125mg / m2 IV. D1, 8 (q3w). Arm3 (Biomarkers: BRCA 1/2 wildtype and \<3 CD8+ TILs count): Bevacizumab 7.5mg/kg IV D1, 15 + Nab-paclitaxel 100mg / m2 IV D1, 8, 15 (Q4w). Treatment would continue until disease progression, intolerable toxicity, death, withdrawal of consent, or sponsor termination of the study, whichever occurs first.
Investigators
Qinglei Gao
Professor
Tongji Hospital
Eligibility Criteria
Inclusion Criteria
- •Voluntary participation and signing of informed consent
- •Age ≥ 18 years;
- •the Eastern United States cancer cooperation group (ECoG) score 0-1;
- •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;
- •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;
- •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
- •Sufficient organ functions, which is defined as:
- •neutrophil absolute value (ANC) ≥ 1.5 × 109/L
Exclusion Criteria
- •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;
- •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;
- •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;
- •Major surgery within 30 days before the first administration of study treatment; Patients expected to have invasive surgery during treatment;
- •Patients with other malignant tumors;
- •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 \[tumor necrosis factor receptor superfamily member 9 (tnfrsf9)\];
- •Active autoimmune diseases requiring systemic treatment in the past 2 years;
- •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;
- •Known history of human immunodeficiency virus (HIV) infection;
- •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;
Arms & Interventions
Arm 1: Pamiparib+ Bevacizumab
Arm1 (Biomarkers: BRCA 1/2 mutant): Pamiparib 40mg PO. bid. plus Bevacizumab 7.5mg/kg IV. D1 (q3w.).
Intervention: Pamiparib
Arm 1: Pamiparib+ Bevacizumab
Arm1 (Biomarkers: BRCA 1/2 mutant): Pamiparib 40mg PO. bid. plus Bevacizumab 7.5mg/kg IV. D1 (q3w.).
Intervention: Bevacizumab
Arm 2: Tislelizumab + Bevacizumab + Nab-paclitaxel
Arm2 (Biomarkers: BRCA 1/2 wildtype and ≥3 CD8+ TILs count): Tislelizumab 200mg IV. D1 + Bevacizumab 7.5mg/kg IV. D1 + Nab-paclitaxel 125mg / m2 IV. D1, 8 (q3w).
Intervention: Bevacizumab
Arm 2: Tislelizumab + Bevacizumab + Nab-paclitaxel
Arm2 (Biomarkers: BRCA 1/2 wildtype and ≥3 CD8+ TILs count): Tislelizumab 200mg IV. D1 + Bevacizumab 7.5mg/kg IV. D1 + Nab-paclitaxel 125mg / m2 IV. D1, 8 (q3w).
Intervention: Tislelizumab
Arm 2: Tislelizumab + Bevacizumab + Nab-paclitaxel
Arm2 (Biomarkers: BRCA 1/2 wildtype and ≥3 CD8+ TILs count): Tislelizumab 200mg IV. D1 + Bevacizumab 7.5mg/kg IV. D1 + Nab-paclitaxel 125mg / m2 IV. D1, 8 (q3w).
Intervention: Nab paclitaxel
Arm 3: Bevacizumab + Nab-paclitaxel
Arm3 (Biomarkers: BRCA 1/2 wildtype and \<3 CD8+ TILs count): Bevacizumab 7.5mg/kg IV D1, 15 + Nab-paclitaxel 100mg / m2 IV D1, 8, 15 (Q4w).
Intervention: Bevacizumab + Nab paclitaxel (intense dose-dense)
Outcomes
Primary Outcomes
Objective response rate (ORR)
Time Frame: Up to 3 years
ORR is defined as the proportion of patients with complete response(CR) and partial response(PR) assessed by the investigator in accordance with the RECIST 1.1 criteria.
Secondary Outcomes
- Overall survival (OS)(Up to 5 years)
- Disease control rate (DCR)(Up to 5 years)
- Progression-free survival (PFS)(Up to 3 years)
- Duration of remission (DOR)(Up to 3 years)
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability](Up to 5 years)