A Study of Navicixizumab in Patients With Platinum Resistant Ovarian Cancer

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma
• Intervention / Treatment: Drug: navicixizumab; Device: Xerna™ TME Panel

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: OncXerna Therapeutics; Phone Number: 781-907-7810; Email: medical@oncxerna.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• 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 v1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 Adequate organ function

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: navicixizumab; navicixizumab IV; Other Names: navi; Device: Xerna™ TME Panel; RNA-seq-based biomarker platform that classifies any given patient tumor sample into phenotypes based on the dominant biology of the tumor microenvironment (TME).
Active Comparator: Paclitaxel monotherapy; Paclitaxel monotherapy: paclitaxel 80 mg/m2 on Days 1, 8 and 15 of a 28-day cycle	Device: Xerna™ TME Panel; RNA-seq-based biomarker platform that classifies any given patient tumor sample into phenotypes based on the dominant biology of the tumor microenvironment (TME).
Experimental: Navicixizumab monotherapy; Navicixizumab monotherapy: navicixizumab 3 mg/kg Q2W of a 28-day cycle (i.e., Days 1 and 15)	Drug: navicixizumab; navicixizumab IV; Other Names: navi; Device: Xerna™ TME Panel; RNA-seq-based biomarker platform that classifies any given patient tumor sample into phenotypes based on the dominant biology of the tumor microenvironment (TME).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	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)	Up to 2 years
PFS	Progression Free Survival	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DOR	Duration of Response	Up to 2 years
OS	Overall Survival	Up to 2 years
TTR	Time to response	Up to 2 years
DCR	Disease control rate defined as the proportion of patients with stable disease (SD) or a confirmed BOR of CR or PR	Up to 2 years

Collaborators and Investigators

• Sponsor: OncXerna Theraputics, Inc.
• Investigators: Principal Investigator: Kathleen N Moore, MD,MS, University of Oklahoma

Study record dates

Study Major Dates

• Study Start (Anticipated): November 30, 2022
• Primary Completion (Anticipated): November 15, 2023
• Study Completion (Anticipated): August 15, 2024

Study Registration Dates

• First Submitted: September 7, 2021
• First Submitted That Met QC Criteria: September 7, 2021
• First Posted (Actual): September 14, 2021

Study Record Updates

• Last Update Posted (Actual): August 15, 2022
• Last Update Submitted That Met QC Criteria: August 12, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Platinum-Resistant
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Fallopian Tube Diseases; Ovarian Neoplasms; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: ONCX-NAV-G301; 2021-001933-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes