A Study of Zanzalintinib in Participants With Recurrent or Progressive Meningioma

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

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

Study Overview

• Status: Recruiting
• Conditions: Meningioma
• Intervention / Treatment: Drug: Zanzalintinib

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Exelixis Clinical Trials; Phone Number: 1-888-EXELIXIS (888-393-5494); Email: druginfo@exelixis.com
• Study Contact Backup: Name: Backup or International; Phone Number: 650-837-7400

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33176
      • Recruiting
      • Exelixis Site #3
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Exelixis Site #2
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • Exelixis Site #1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key 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

Key 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zanzalintinib; Participants will receive zanzalintinib once daily (QD).	Drug: Zanzalintinib; Administered as specified in the treatment arm.; Other Names: XL092

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR) per Response Assessment in Neuro-oncology (RANO) as Assessed by Blinded Independent Central Review (BICR)	Up to approximately 12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free Survival at 6 Months (PFS-6) per RANO as Assessed by BICR and Investigator	Up to 6 months
Duration of Response (DOR) per RANO as Assessed by BICR and Investigator	Up to approximately 48 months
Progression-free Survival (PFS) per RANO as Assessed by BICR and Investigator	Up to approximately 48 months
Overall Survival (OS)	Up to approximately 48 months
Number of Participants with Treatment-emergent Adverse Events (TEAEs)	Up to approximately 48 months
Change from Baseline in Neurologic Function as Measured by the Neurologic Assessment in Neuro-oncology (NANO) Scale Score	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	Baseline up to approximately 13 months

Collaborators and Investigators

• Sponsor: Exelixis
• Investigators: Study Director: Study Director, Exelixis

Study record dates

Study Major Dates

• Study Start (Estimated): May 31, 2026
• Primary Completion (Estimated): February 29, 2028
• Study Completion (Estimated): September 30, 2029

Study Registration Dates

• First Submitted: February 19, 2026
• First Submitted That Met QC Criteria: February 19, 2026
• First Posted (Actual): February 24, 2026

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Brain; Meningioma; Intracranial Neoplasms; Atypical Meningioma; Anaplastic Meningioma; Recurrent Meningioma; XL092; Zanzalintinib; Progressive Meningioma; Grade 1 Meningioma; Grade 2 Meningioma; Grade 3 Meningioma; Extracranial Meningioma
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Meningioma; Brain Neoplasms
• Other Study ID Numbers: XL092-201

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: No