A Study of Zanzalintinib in Participants With Recurrent or Progressive Meningioma

Official title

A Phase 2, Single-Arm, Multicenter, Open-Label Study of Zanzalintinib in Participants With Recurrent or Progressive Meningioma

Overview

The objective of the study is to evaluate efficacy and safety of zanzalintinib in participants with recurrent or progressive meningioma refractory to standard therapies.

Interventions

• Drug Zanzalintinib
  Administered as specified in the treatment arm.

Primary outcome measures

• Objective Response Rate (ORR) per Response Assessment in Neuro-oncology (RANO) as Assessed by Blinded Independent Central Review (BICR) [Time frame: Up to approximately 12 months]

Secondary outcome measures (7)

• Progression-free Survival at 6 Months (PFS-6) per RANO as Assessed by BICR and Investigator [Time frame: Up to 6 months]
• Duration of Response (DOR) per RANO as Assessed by BICR and Investigator [Time frame: Up to approximately 48 months]
• Progression-free Survival (PFS) per RANO as Assessed by BICR and Investigator [Time frame: Up to approximately 48 months]
• Overall Survival (OS) [Time frame: Up to approximately 48 months]
• Number of Participants with Treatment-emergent Adverse Events (TEAEs) [Time frame: Up to approximately 48 months]
• Change from Baseline in Neurologic Function as Measured by the Neurologic Assessment in Neuro-oncology (NANO) Scale Score [Time frame: Baseline up to approximately 13 months]
• Change from Baseline in Health-related Quality of Life (HRQoL) as Measured by the EuroQol 5-dimension 5-level Questionnaire (EQ-5D-5L) Score [Time frame: Baseline up to approximately 13 months]

Eligibility criteria

Inclusion criteria

• Histologically confirmed World Health Organization (WHO) grade 1, 2, or 3 meningioma.
• Developed recurrent disease or progressive disease (PD) after receiving standard therapy (for example, surgery and/or radiation) or have been deemed ineligible to receive these therapies. At least 1 prior course of meningioma-directed radiotherapy is required, if not contraindicated.
• Radiologically documented progression of any existing tumor (growth > 15% of the bidimensional enhancing tumor within the prior 6 months or appearance of new lesions (including intra and extracranial manifestations).
• For participants treated with external beam radiation, interstitial brachytherapy, or radiosurgery, an interval ≥ 24 weeks must have elapsed from completion of therapy to initiation of treatment.
• Measurable disease by RANO meningioma criteria as determined by the investigator, obtained ≤ 14 days prior to initiation of treatment.
• Karnofsky performance status (KPS) ≥ 60%.
• Demonstrate adequate organ and marrow function within 14 days of treatment initiation

Exclusion criteria

• Prior history of hypertensive encephalopathy at any time.
• Extracranial lesions invading major blood vessels including, but not limited to, inferior vena cava, pulmonary artery, or aorta.
• Contraindication to magnetic resonance imaging (MRI).
• Local therapy (surgery and/or radiation therapy) is indicated per investigator
• Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks or 5 half-lives, whichever is shorter, before initiation of treatment. There is no limit on prior systemic therapies
• Prior Surgery - completed wound healing must occur prior to initiation of treatment; ≥ 8 weeks for major surgery, ≥ 7 days for minor surgery, including stereotactic biopsies.
• The participant has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:

• Cardiovascular disorders, including uncontrolled hypertension,
• Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation,
• Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 milliliters \[mL\]) of red blood within 12 weeks before initiation of treatment or other history of significant bleeding (eg, intracranial hemorrhage/bleeding), or
• Other clinically significant disorders.
• Requirement for hemodialysis or peritoneal dialysis.
• History of solid organ or allogeneic stem cell transplant.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 12 centers

• University of Alabama — Birmingham
• Mayo Clinic_Arizona — Phoenix
• Mayo Clinic_Jacksonville — Jacksonville
• Baptist Health Miami Cancer Institute — Miami
• Washington University School of Medicine — St Louis
• Memorial Sloan-Kettering Cancer Center — New York
• Mayo Clinic_Rochester — Rochester
• Duke University — Durham
• … and 4 more centers

Identifiers

NCT: NCT07428616 · XL092-201

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗