A Study of Zanzalintinib in Participants With Recurrent or Progressive Meningioma

• Zanzalintinib (Drug), also known as XL092: Administered as specified in the treatment arm.

Primary outcomes

• 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 outcomes

• 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]

Sex: All, ages: 18 Years to any

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 Director, Study director, Exelixis