Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as JZP3507
ONC206 · 4 trials · 33 indications
ORR is the best response of confirmed complete response (CR), partial response (PR), or minor response (MR) during the study, as per RANO criteria
ORR defined as the number of participants with a confirmed complete response (CR) or partial response during the study, as per RECIST v1.1.
A DLT is defined as a treatment-related adverse event (AE) or abnormal laboratory value that occurs in the first cycle of treatment (Cycle 1 for Arm A and D; Cycle 0 for Arm B and C), meets criteria for DLT as outlined below and is assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications, and is judged by the investigator to be related to ONC206 as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0).
The Bayesian optimal interval (BOIN) design will be used to find the MTD within each arm. MTD is selected based on isotonic regression and this computation is implemented by the shiny app "BOIN" available at http://www.trialdesign.org. Specifically, select as the MTD the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate. If there are ties, select the higher dose level when the isotonic estimate is lower than the target toxicity rate and select the lower dose level when the isotonic estimate is greater than or equal to the target toxicity rate.
MTD was determined by testing increasing doses up to 200 mg twice daily for 3 successive days a week. MTD reflects the highest dose of drug that did not cause a Dose-Limiting Toxicity (DLT) in \>33% of participants. DLTs will be assessed in the first course of each cohort (28 days), and refer to a study drug-related or possibly related event that meets 1 of the following criteria defined in the subsequent Primary Outcome Measure using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE 5.0).
DLTs will be assessed in the first course of each cohort (28 days), and refer to a study drug-related or possibly related event that meets 1 of the following criteria using NCI CTCAE 5.0: * Grade 3 or higher non-hematologic toxicity. * Grade 4 hematologic toxicity (ANC \<0.5 × 109/L and platelet count \<25 × 109/L). Lymphopenia is not considered a DLT. A confirmed DLT requires 2 consecutive measurements separated by 48 hours. * Grade 3 neutropenia (absolute neutrophil count \[ANC\] \<1.0 × 109/L) with elevated fever (\>101°F). A confirmed DLT requires 2 consecutive measurements. * Grade 3 thrombocytopenia with clinically significant bleeding. * Inability to receive the scheduled Cycle 2, Day 1 dose of study drug within 14 days due to study drug-related toxicity persisting from Cycle 1 or study drug-related toxicity newly encountered on Day 1 of Cycle 2.
| Arm | Type | Description |
|---|---|---|
| JZP3507 (ONC206) | EXPERIMENTAL | - |
| Stage 1 Participants | EXPERIMENTAL | 150 mg ONC206 BID TIW |
| Stage 2: Dose 1 | EXPERIMENTAL | Participants receiving ONC206 at dose (To be Determined \[TBD\] post stage 1). |
| Stage 2: Dose 2 | EXPERIMENTAL | Participants receiving ONC206 at dose (TBD post stage 1). |
| Arm A: ONC206 for participants with diffuse midline gliomas + prior therapy | EXPERIMENTAL | Participants receive ONC206 orally (PO) up to six times per week. Cycles repeat every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity. In case the participant receives clinical benefit from the treatment, treatment can proceed up to 24 months. |
| Arm B: ONC206 + radiation therapy for newly diagnosed participants | EXPERIMENTAL | Participants undergo standard of care radiation therapy daily 5 days a week and receive ONC206 PO up to six times per week. Cycles repeat every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity. In case the participant receives clinical benefit from the treatment, treatment can proceed up to 24 months. |
| Arm C: ONC206 + radiation therapy, DMGs with evidence of first progression but previously untreated | EXPERIMENTAL | Participants undergo standard of care radiation therapy daily 5 days a week and receive ONC206 PO up to six times per week. Cycles repeat every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity. In case the participant receives clinical benefit from the treatment, treatment can proceed up to 24 months. |
| Arm D: ONC206 Therapy, Primary malignant CNS tumors with progression | EXPERIMENTAL | Participants receive ONC206 PO once a day (QD) up to six times per week. Cycles repeat every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity. In case the participant receives clinical benefit from the treatment, treatment can proceed up to 24 months. |
| ONC206 | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| JZP3507 | DRUG | Participants will receive oral JZP3507 monotherapy twice daily, on 3 consecutive days per week in 28-day cycles. |
| ONC206 | DRUG | 150 mg BID TIW |
| ONC206: Dose 1 | DRUG | - |
| ONC206: Dose 2 | DRUG | - |
| Standard of Care Radiation Therapy | RADIATION | Undergo RT |
| Optional Proton (1H) MR spectroscopy (MRS) | PROCEDURE | Optional imaging procedure |
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 mening...
ONC206 is an investigational small molecule being studied for advanced pheochromocytoma and paraganglioma, central nervous system neoplasms, and diffuse midline glioma (DMG). It is in Phase 2 development for advanced pheochromocytoma and paraganglioma and Phase 1 for other CNS tumors.
ONC206 targets ClpP and DRD2. ClpP is a mitochondrial protease, and DRD2 is a dopamine receptor. The drug is being evaluated as an oral small molecule in oncology clinical trials.
ONC206 is being developed by Jazz Pharmaceuticals plc, traded on the NASDAQ under the ticker JAZZ. The company is conducting clinical trials of the drug in the United States, Netherlands, and Switzerland.
ONC206 is in Phase 2 clinical development for advanced pheochromocytoma and paraganglioma. It is also being studied in Phase 1 trials for diffuse midline glioma and other recurrent malignant CNS tumors. The drug is investigational and not yet approved.
ONC206 is being studied in three recruiting trials: NCT07282587, a Phase 2 study in advanced pheochromocytoma and paraganglioma with 90 participants; NCT04732065, a Phase 1 study in newly diagnosed and recurrent diffuse midline gliomas and other CNS tumors with 208 participants; and NCT04541082, a Phase 1 study in recurrent and rare primary CNS neoplasms with 102 participants.
Yes, ONC206 is also known as JZP3507. The Phase 2 trial NCT07282587 in advanced pheochromocytoma and paraganglioma refers to the drug as ONC206 (JZP3507), confirming the two names refer to the same investigational compound.