An Open Label Randomized Study of Navicixizumab Plus Paclitaxel and Navicixizumab Monotherapy in Comparison to Paclitaxel Monotherapy in Patients With Platinum-Resistant Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 400
- 主要终点
- ORR
研究概览
简要总结
This is a Phase 3, randomized, open-label, 2-stage, multicenter study of navicixizumab with or without paclitaxel compared with paclitaxel monotherapy in patients with platinum-resistant advanced epithelial ovarian cancer and specific biomarkers, as measured by the proprietary and validated Xerna™ TME Panel biomarker assay. Eligible patients must have received at least 2 prior regimens but not more than 5 prior regimens, including treatment with a monoclonal antibody angiogenesis inhibitor (e.g., bevacizumab), must be considered platinum-resistant, and must be considered appropriate to receive single-agent paclitaxel chemotherapy as a next line of therapy. All patients must be willing and able to provide a formalin-fixed paraffin embedded (FFPE) archive or core tumor sample collected during screening for classification as B+ or B- biomarker status based on RNA expression data from the Xerna™ TME Panel biomarker assay. The co-primary efficacy endpoints are ORR by RECIST v1.1 and PFS (as assessed by blinded independent radiological review [BIRR]) analyzed at different timepoints. Analysis of the ORR primary efficacy endpoints will occur at the end of Stage 1 and at the end of Stage 2; the PFS primary efficacy endpoint will be analyzed at the end of Stage 2.
详细描述
This is a Phase 3, randomized, open-label, 2-stage, multicenter study of navicixizumab with or without paclitaxel compared with paclitaxel monotherapy in patients with platinum-resistant advanced epithelial ovarian cancer and specific biomarkers, as measured by the proprietary and validated Xerna™ TME Panel biomarker assay. Eligible patients must have received at least 2 prior regimens but not more than 5 prior regimens, including treatment with a monoclonal antibody angiogenesis inhibitor (e.g., bevacizumab), must be considered platinum-resistant, and must be considered appropriate to receive single-agent paclitaxel chemotherapy as a next line of therapy. All patients must be willing and able to provide a formalin-fixed paraffin embedded (FFPE) archive or core tumor sample collected during screening for classification as B+ or B- biomarker status based on RNA expression data from the Xerna™ TME Panel biomarker assay. The co-primary efficacy endpoints are ORR by RECIST v1.1 and PFS (as assessed by blinded independent radiological review [BIRR]) analyzed at different timepoints. Analysis of the ORR primary efficacy endpoints will occur at the end of Stage 1 and at the end of Stage 2; the PFS primary efficacy endpoint will be analyzed at the end of Stage 2.
Patients will be stratified by Xerna™ TME Panel status and region and randomized to the following treatment arms according to the corresponding study stage randomization ratios. Enrollment will proceed from Stage 1 to Stage 2 without interruption:
Stage 1 treatment arms (4:4:1 randomization):
- Combination navicixizumab + paclitaxel: navicixizumab 3 mg/kg once every 2 weeks (Q2W) of a 28-day cycle (i.e., on Days 1 and 15); paclitaxel 80 mg/m2 on Days 1, 8 and 15 of a 28-day cycle
- Paclitaxel monotherapy: paclitaxel 80 mg/m2 on Days 1, 8 and 15 of a 28-day cycle
- Navicixizumab monotherapy: navicixizumab 3 mg/kg Q2W of a 28-day cycle (i.e., on Days 1 and 15)
• Stage 2 treatment arms (2:2:3 randomization):
- Combination navicixizumab + paclitaxel: navicixizumab 3 mg/kg Q2W of a 28-day cycle (i.e., on Days 1 and 15); paclitaxel 80 mg/m2 on Days 1, 8 and 15 of a 28-day cycle
- Paclitaxel monotherapy: paclitaxel 80 mg/m2 on Days 1, 8 and 15 of a 28-day cycle
- Navicixizumab monotherapy: navicixizumab 3 mg/kg Q2W of a 28-day cycle (i.e., on Days 1 and 15) Within each treatment arm, patients will be stratified to a B+ or B- cohort based on their Xerna™ TME Panel biomarker assay results during screening.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patient must have epithelial ovarian, fallopian tube, or primary peritoneal cancer
- •Patients must have received ≥2 and not more than 5 prior therapies, including at least 1 line of therapy containing bevacizumab (or biosimilar).
- •Patients must be considered platinum-resistant, defined as progression within 6 months from completion of a platinum-containing therapy
- •Patient must be considered appropriate for treatment with weekly paclitaxel monotherapy as the next line of therapy.
- •Patient must be willing and able to provide an FFPE archival or core tumor sample for determination of biomarker status on the Xerna™ TME Panel biomarker assay (positive or negative) prior to study treatment.
- •Presence of at least one measurable lesion, as defined by RECIST v1.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 Adequate organ function
排除标准
- •Non-epithelial ovarian carcinoma.
- •Ovarian tumors with low malignant potential (i.e., borderline tumors).
- •Primary platinum-refractory disease (defined as progression during or within 4 weeks after completion of the first platinum regimen).
- •Patient has received an anti-angiogenic product other than bevacizumab or biosimilar.
- •Patient has congestive heart failure
- •Patient has a history of myocardial infarction, cerebral vascular accident, or transient ischemic attacks within 6 months
- •Patient has a history of cardiac ischemia or heart failure within 6 months
- •Baseline B-type natriuretic peptide (BNP) value >100 pg/mL or N-terminal-proBNP (NT-proBNP) value of > 125 pg/mL.
- •LVEF <50%.
- •Peak tricuspid velocity >3.0 m/s on Doppler ECHO.
- •Clinically significant ECG abnormality, as assessed by the investigator
- •Blood pressure (BP) >140/90 mmHg
- •History of bowel obstruction, including sub-occlusive disease, related to the underlying disease
- •Hemoptysis >2.5 mL within 8 weeks prior
- •Major surgical procedure, or significant traumatic injury within 28 days
- •Uncontrolled seizure disorder or active neurologic disease
- •Patients with a cardiac aneurysm.
研究组 & 干预措施
Combination navicixizumab + paclitaxel
Combination navicixizumab + paclitaxel: navicixizumab 3 mg/kg Q2W of a 28 day cycle (i.e., Days 1 and 15); paclitaxel 80 mg/m2 on Days 1, 8 and 15 of a 28 day cycle
干预措施: navicixizumab (Drug)
Combination navicixizumab + paclitaxel
Combination navicixizumab + paclitaxel: navicixizumab 3 mg/kg Q2W of a 28 day cycle (i.e., Days 1 and 15); paclitaxel 80 mg/m2 on Days 1, 8 and 15 of a 28 day cycle
干预措施: Xerna™ TME Panel (Device)
Paclitaxel monotherapy
Paclitaxel monotherapy: paclitaxel 80 mg/m2 on Days 1, 8 and 15 of a 28-day cycle
干预措施: Xerna™ TME Panel (Device)
Navicixizumab monotherapy
Navicixizumab monotherapy: navicixizumab 3 mg/kg Q2W of a 28-day cycle (i.e., Days 1 and 15)
干预措施: navicixizumab (Drug)
Navicixizumab monotherapy
Navicixizumab monotherapy: navicixizumab 3 mg/kg Q2W of a 28-day cycle (i.e., Days 1 and 15)
干预措施: Xerna™ TME Panel (Device)
结局指标
主要结局
ORR
时间窗: Up to 2 years
Overall Response Rate defined as the proportion of patients with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR), by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
PFS
时间窗: Up to 2 years
Progression Free Survival
次要结局
- DCR(Up to 2 years)
- OS(Up to 2 years)
- TTR(Up to 2 years)
- DOR(Up to 2 years)