A Study of JZP3507 (ONC206) in Recurrent Grade 2 or 3 Meningioma

A Phase 2 Study to Investigate Efficacy, Safety, Tolerability, and Pharmacokinetics of JZP3507 (ONC206) in Adults With Recurrent Grade 2 or 3 Meningioma

This study will recruit participants with Grade 2 and 3 meningiomas who have failed prior therapy. Participants will receive oral doses of JZP3507. The antitumor activity and safety of JZP3507 will be evaluated.

Study Overview

• Status: Not yet recruiting
• Conditions: Meningioma
• Intervention / Treatment: Drug: JZP3507

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trial Disclosures & Transparency; Phone Number: 215-832-3750; Email: ClinicalTrialDisclosure@jazzpharma.com

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94109
      • Sutter Health
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Mass General
  • New York
    • New York, New York, United States, 10016
      • NYU- Langone Health
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah - Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

Age

1. Is ≥ 18 years of age at the time of signing the informed consent.

   Type of Participant and Disease Characteristics

2. Has histologically confirmed Grade 2 or 3 meningioma.
3. Has failed, is not a candidate for, or has declined standard of care treatment for meningioma. Note: There is no limit on the number of prior systemic therapies.
4. Has measurable disease, as assessed by the investigator. Measurable disease is defined as at least one lesion measuring ≥ 10 mm on perpendicular dimensions by contrast-enhanced MRI performed within 28 days prior to study enrollment.
5. Has progressive disease (PD) per Response Assessment in Neuro-Oncology (RANO) criteria, as assessed by the investigator using axial, contrast-enhanced T1-weighted magnetic resonance imaging (MRI). PD is defined as an increase in size of the measurable primary lesion on imaging by at least 15% in sum of product of target lesions since last treatment or between scans separated by no more than 6 months. The presence of a new lesion would also qualify as PD.
6. Is able to submit historic disease-related imaging from at least 9 months prior to study entry to central imaging vendor (preferably all available disease-related imaging from initial diagnosis onwards).
7. Is able to swallow oral tablets.
8. Has a Karnofsky Performance Status (KPS) of at least 70.

9. Has laboratory test results meeting the following parameters within 14 days before the start of study intervention:

   1. Absolute neutrophil count ≥ 1.0 × 109/L and platelets ≥ 75 × 109/L.
   2. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (participants with Gilbert's syndrome may be included with total bilirubin > 1.5 × ULN if direct bilirubin is ≤ 1.5 × ULN).
   3. Aspartate (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN. Note: For participants with documented baseline liver metastasis, the following limits will apply: ≤ 5 × ULN for transaminase.
   4. Creatinine clearance ≥ 50 mL/min as calculated by the Cockcroft Gault equation (or estimated glomerular filtration rate [eGFR] > 60 mL/min/1.73 m2) or serum creatinine ≤ 1.5 × ULN.
10. Has an expected survival of at least 12 weeks, as predicted by the physician.
11. Is able to submit at least 10 (preferably ≥ 15 slides, if available) unstained formalin-fixed paraffin-embedded (FFPE) slides or a tissue block with sufficient material for ~15 slides from participant's tumor tissue to the sponsor.

12. Has had an MRI within 28 days before the start of study intervention, with the corticosteroid dose stable or decreasing at least 5 days prior to the scan.

    Sex and Contraceptive/Barrier Requirements

13. Agrees to the following based on sex assigned at birth: is not of child-bearing potential or agrees to use appropriate contraception, as defined in protocol, for males and females.

Key Exclusion Criteria:

Medical Conditions

1. Has known hypersensitivity to JZP3507, dordaviprone, or any excipient used in the JZP3507 study intervention formulation.
2. Has active cardiac disease/condition as defined in the protocol.
3. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Exceptions include participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.

4. Has an active infection that requires systemic therapy.

   Prior/Concomitant Therapy

5. Has received any of the following interventions within the specified time periods before the first dose of study intervention or plans to receive any of the following interventions during study participation:

   1. Prior anticancer therapy or investigational agents within 28 days or 5 half-lives, whichever is shorter.
   2. Antibody-based anticancer therapy within 42 days.
   3. Radiotherapy within 24 weeks (~6 months).
   4. Strong CYP3A4 inhibitors within 14 days.
   5. Strong CYP3A4 inducers within 14 days.
   6. Major surgery, open biopsy, or significant traumatic injury within 30 days.

6. Has uncontrolled intercurrent illness or any other medical, psychiatric, or social condition that, in the opinion of the investigator, may interfere with participant safety or the ability to comply with study requirements.

   Prior/Concurrent Clinical Study Experience

7. Has previous exposure to JZP3507 or dordaviprone from any source.

   Diagnostic Assessments

8. Has optic nerve sheath meningioma, extracranial meningioma, or meningioma primarily localized spinal cord.
9. Has more than 3 measurable lesions.

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: JZP3507 (ONC206)	Drug: JZP3507; Participants will receive oral JZP3507 monotherapy twice daily, on 3 consecutive days per week in 28-day cycles.; Other Names: ONC206

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) as Assessed by Response Assessment in Neuro-Oncology (RANO) Criteria and Evaluated by Blinded Independent Central Review (BICR)	ORR is the best response of confirmed complete response (CR), partial response (PR), or minor response (MR) during the study, as per RANO criteria	From first dose until death, withdrawal of consent, or lost to follow-up, up to 40 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	DOR is the time from the first objective response (CR, PR, or MR) that is subsequently confirmed to documented progressive disease (PD) per RANO criteria or death from any cause.	From first dose until death, withdrawal of consent, or lost to follow-up, up to 64 months.
Time to Response (TTR)	TTR is the time from the first dose of the study intervention to the first objective response (CR, MR, or PR) subsequently confirmed per RANO criteria.	From first dose until death, withdrawal of consent, or lost to follow-up, up to 64 months.
Disease Control Rate (DCR)	Proportion of participants who achieved disease control in the study.	From first dose until death, withdrawal of consent, or lost to follow-up, up to 64 months.
Progression-Free Survival (PFS)	PFS is the time from the first dose of study intervention to the date of first documented PD per RANO criteria (evaluated by BICR) or death from any cause, whichever occurs first.	From first dose to date of documented disease progression or death, up to 64 months.
Overall Survival (OS)	OS is the time from the first dose of the study intervention to death from any cause.	From first dose until death, or up to 64 months.
Incidence of Grade 3 or higher Treatment-Emergent Adverse Events (TEAEs)		Up to 64 months.
Number of Adverse Events (AEs) Resulting in Study Discontinuation		Up to 64 months.
Maximum Observed Plasma Concentration (Cmax) of JZP3507		Up to 64 months.
Time of Maximum Observed Plasma Concentration (Tmax) of JZP3507		Up to 64 months.
Area Under the Concentration-Time Curve Over a Time interval (AUC(0-τ)) of JZP3507		Up to 64 months.
Terminal Elimination Half-life ( t½) of JZP3507		Up to 64 months.
Apparent Oral Clearance (CL/F)		Up to 64 months.
Apparent Volume of Distribution After Oral Dose (Vz/F)		Up to 64 months.

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals
• Collaborators: Chimerix, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): October 25, 2028
• Study Completion (Estimated): October 16, 2031

Study Registration Dates

• First Submitted: April 10, 2026
• First Submitted That Met QC Criteria: April 10, 2026
• First Posted (Actual): April 16, 2026

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Recurrent Meningioma; ONC206; JZP3507; Grade 2 Meningioma; Grade 3 Meningioma; H3 K27me3 loss
• Additional Relevant MeSH Terms: 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; ONC206
• Other Study ID Numbers: JZP3507-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with ICMJE requirements, Jazz Pharmaceuticals may provide qualified external researchers access to individual participant data (IPD) and clinical trial data that underlie the results of this trial upon request. Qualified researchers can submit a request on https://www.jazzpharma.com/science/clinical-trial-data-sharing/ as outlined. Jazz Pharmaceuticals reserves the right not to consider a request. For inquiries about Jazz's data sharing policy, contact clinicaldatasharing@jazzpharma.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No