Study of ONC206 (JZP3507) in Advanced Pheochromocytoma and Paraganglioma

A Phase 2 Study of ONC206 in Advanced Pheochromocytoma and Paraganglioma

This is a two-stage Phase 2 trial evaluating the efficacy and safety of ONC206 in participants with Pheochromocytoma and Paraganglioma (PCPG).

Study Overview

• Status: Recruiting
• Conditions: Advanced Pheochromocytoma and Paraganglioma; PCPG
• Intervention / Treatment: Drug: ONC206; Drug: ONC206: Dose 1; Drug: ONC206: Dose 2

Detailed Description

Two-Stage Study to evaluate ONC206 as monotherapy doses:

Stage 1: Participants will receive 150mg ONC206 twice daily, on three consecutive days per week (BID TIW) in each 28-day cycle.

• Part A: Initial number of participants will be monitored.
• Part B: If a set number of participants have a response, then more participants will be enrolled and treated.

Stage 2: If Stage 1 meets the planned response, the study will proceed, and participants will be randomized 1:1 to receive 1 of 2 ONC206 dose levels.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

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

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA
    • Palo Alto, California, United States, 94604
      • Recruiting
      • Stanford
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Not yet recruiting
      • U of Colorado
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Not yet recruiting
      • U of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo-Rochester
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University
  • New York
    • New York, New York, United States, 10032
      • Not yet recruiting
      • Columbia University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • PENN
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Not yet recruiting
      • UTAH

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

1. Has histologically confirmed pheochromocytoma or paraganglioma that is unresectable as determined by the Investigator.
2. Has failed, is not a candidate for, or has declined standard of care treatment for PCPG. There is no limit on the number of prior systemic therapies.
3. Must have measurable disease per RECIST v1.1, as assessed by the Investigator.
4. Has adequately controlled blood pressure defined as blood pressure ≤150/90 mmHg and with no change in antihypertensive medications (for participants with concomitant hypertension) for at least 14 days before the first dose of study treatment.
5. Is ≥18 years of age.
6. Is able to swallow oral tablets.
7. Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2, assessed within 7 days before the first dose of study treatment.
8. Has laboratory test results meeting the following parameters within 14 days before the first dose of study treatment
9. Has an expected survival of at least 12 weeks, as predicted by the physician.
10. Has pharmacologic control of catecholamine-associated symptoms if participant has functional disease.

Exclusion criteria:

1. Has known hypersensitivity to ONC206 or any excipient used in the ONC206 study treatment formulation.

2. Has active cardiac disease/condition including any of the following:

   1. Corrected QT interval (QTc) >480 msec (based on the mean from triplicate electrocardiogram [ECGs] performed during Screening).
   2. History of documented congestive heart failure (New York Heart Association function classification III-IV).
   3. Unstable angina, acute myocardial infarction, or arterial bypass or percutaneous transluminal coronary angioplasty within 6 months before the first dose of study treatment.
3. Has previous exposure to ONC206 or dordaviprone (ONC201) from any source.
4. 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, or Von Hippel-Lindau disease-associated tumors that do not require immediate surgery or intervention.

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

   • a. Any prior anticancer therapy or investigational agents within 4 weeks or 5 half-lives, whichever is shorter. Note: Denosumab and zoledronic acid are permissible.

     **i. Any treatment with somatostatin analog or lanreotide within 21 days before the baseline Positron Emission Tomography (PET) scan.

   • b. Strong cytochrome P450 (CYP) inhibitors within 14 days. c. Strong CYP inducers within 14 days. d. Any radiotherapy within 14 days. e. Any major surgery, open biopsy or significant traumatic injury within 1 month (30 days).
6. Is pregnant, breastfeeding, or planning to become pregnant while receiving study treatment or within 3 months after the last dose.
7. 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.
8. Has unresolved toxicities from previous locoregional, systemic, or any other therapies, defined as toxicities (other than Grade ≤2 neuropathy or alopecia) not yet resolved to the National Cancer Institute Common Terminology Criteria for Adverse Events Grade ≤1, or baseline and considered clinically significant; consult with Medical Monitor.
9. Has an active infection that requires systemic therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stage 1 Participants; 150 mg ONC206 BID TIW	Drug: ONC206; 150 mg BID TIW
Experimental: Stage 2: Dose 1; Participants receiving ONC206 at dose (To be Determined [TBD] post stage 1).	Drug: ONC206: Dose 1
Experimental: Stage 2: Dose 2; Participants receiving ONC206 at dose (TBD post stage 1).	Drug: ONC206: Dose 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	ORR defined as the number of participants with a confirmed complete response (CR) or partial response during the study, as per RECIST v1.1.	Up to 36 months.

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of Response (DOR)	Up to 36 months.
Time to Response (TTR)	Up to 36 months.
Disease Control Rate (DCR)	Up to 36 months.
Progression Free Survival (PFS) by RECIST v1.1	Up to 36 months.
Overall Survival (OS)	Up to 36 months.
Change from Baseline in Antihypertensive Medication Dose	Up to 36 months.
Change from Baseline in Biochemical Response (Metanephrines/Disease Markers)	Up to 36 months.
Incidence of Adverse Events (AEs)	Up to 36 months.
Number of Participants with Clinically Significant Changes from Baseline in Clinical Laboratory Parameters	Up to 36 months.
Number of Participants with Grade 4+ Clinical Laboratory Parameters	Up to 36 months.
Number of Participants with Clinically Significant Changes from Baseline in Electrocardiogram (ECG) Parameters	Up to 36 months.
Maximum Observed Concentration of ONC206	Up to 36 months.
Time of Maximum Observed Concentration (Tmax) of ONC206	Up to 36 months.
Area Under the Concentration-Time Curve Extrapolated to Infinity (AUCinf)	Up to 36 months.
Area Under the Concentration Time Curve Over the Dosing Interval	Up to 36 months.
Terminal Half-Life (t1/2) of ONC206	Up to 36 months.
Change from Baseline in European Organization for the Research and Treatment of Cancer Quality of Life-Core Questionnaire (EORTC-QLQ-C30)	Up to 36 months.
Change from Baseline in Functional Assessment of Cancer Therapy - Bone Pain (FACT-BP)	Up to 36 months.

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2026
• Primary Completion (Estimated): December 15, 2028
• Study Completion (Estimated): December 15, 2028

Study Registration Dates

• First Submitted: December 5, 2025
• First Submitted That Met QC Criteria: December 5, 2025
• First Posted (Actual): December 15, 2025

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: PCPG; ONC206; JZP3507
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Paraganglioma; ONC206
• Other Study ID Numbers: ONC206-002

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
• product manufactured in and exported from the U.S.: Yes