Brief Title
A Study of Navicixizumab in Patients With Platinum Resistant Ovarian Cancer
Official Title
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
Brief Summary
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.
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 Phase
Phase 3
Study Type
Interventional
Primary Outcome
ORR
Secondary Outcome
OS
Condition
Ovarian Cancer
Intervention
navicixizumab
Study Arms / Comparison Groups
Combination navicixizumab + paclitaxel
Description: 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
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
400
Start Date
November 30, 2022
Completion Date
August 15, 2024
Primary Completion Date
November 15, 2023
Eligibility Criteria
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.
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Kathleen N Moore, MD,MS, 781-907-7810, [email protected]
Administrative Informations
NCT ID
NCT05043402
Organization ID
ONCX-NAV-G301
Secondary IDs
2021-001933-38
Responsible Party
Sponsor
Study Sponsor
OncXerna Theraputics, Inc.
Study Sponsor
Kathleen N Moore, MD,MS, Principal Investigator, University of Oklahoma
Verification Date
August 2022