A Study of Navicixizumab in Patients With Platinum Resistant Ovarian Cancer

Overview

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.

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. Patients in both stages will have radiologic tumor assessments every 8 weeks (±1 week), regardless of treatment delays, until objective disease progression, initiation of subsequent anticancer therapy, withdrawal of consent, death, or end of study, whichever occurs first. All patients will continue to receive study treatment until progressive disease (PD) per RECIST v1.1 (as assessed by the investigator), the development of unacceptable toxicity, withdrawal of consent, or another protocol-defined discontinuation criteria is met, whichever occurs first, or until the sponsor terminates the study. Treatment decisions (i.e., whether to continue or discontinue the study medication) should not be made based on CA-125 levels. Progression during protocol treatment cannot be declared on the basis of CA 125 alone. All patients who discontinue study treatment for any reason will be followed for survival at 3-month intervals until death or withdrawal of consent, whichever occurs first. Survival follow-up will continue for 12 months after the last patient is enrolled or approximately 75% of the population has died, whichever is later.