ONC206 for Brain Cancer

Overseen By Clinical Trial Disclosure & Transparency

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Jazz Pharmaceuticals

Must not be taking: Warfarin, Strong CYP inhibitors

Disqualifiers: Cardiac disease, Stroke, Epilepsy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

102 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ONC206 for patients with brain cancer. The goal is to assess the drug's safety and determine the optimal dose that avoids serious side effects. It targets individuals whose brain cancer has returned after standard treatments like surgery or radiation and who lack other treatment options. Participants should have a confirmed brain tumor diagnosis and have tried other cancer treatments without success. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain medications like strong inhibitors or inducers of specific liver enzymes (CYP3A4, 2D6, 1A2, 2C9, and 2C19) within 14 days before starting the study drug and throughout the study. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that ONC206 is likely to be safe for humans?

Research shows that ONC206 is in the early stages of testing to determine its safety for humans. Researchers are studying this treatment for its effects on brain cancer. It works by triggering a "stress response" in tumor cells, which can help destroy them.

Since ONC206 is in a Phase 1 trial, the main goal is to find the safest dose and identify any serious side effects. Limited safety information is available, but this phase is crucial to understand how well people can handle the treatment. Although detailed safety data is not yet available, this stage helps ensure that any serious reactions are detected early.

In lab studies, ONC206 has demonstrated strong effects against cancer cells, which is promising. However, human trials are just starting, so ongoing research will provide more detailed safety information as it progresses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for brain cancer?

ONC206 is unique because it targets brain cancer cells through a novel mechanism of action. While most treatments for brain cancer, like surgery, chemotherapy, and radiation, aim to eliminate or shrink the tumor, ONC206 works by selectively inhibiting specific pathways that are critical for cancer cell survival and proliferation. Researchers are excited about this approach as it offers the potential for a more precise attack on cancer cells with potentially fewer side effects compared to traditional treatments. This innovative strategy could lead to more effective and safer treatment options for patients battling brain cancer.

What evidence suggests that ONC206 might be an effective treatment for brain cancer?

Research has shown that ONC206, the investigational treatment in this trial, may help treat brain cancers, particularly glioblastomas and diffuse midline gliomas. Studies have found that ONC206 can kill cancer cells and reduce levels of MGMT, a protein that makes tumors resistant to chemotherapy. In early animal tests, ONC206, alone or with other treatments, shrank tumors and extended survival. These findings suggest that ONC206 could be a strong treatment option, and further research is underway to confirm its effectiveness in humans. ^{4 5 6 7 8}

Who Is on the Research Team?

Jing Wu, MD, PhD

Principal Investigator

Center for Clinical Research, National Cancer Institute, National Institutes of Health

Are You a Good Fit for This Trial?

Adults over 18 with recurrent brain tumors, who are in good physical condition (KPS ≥70), have normal organ/marrow function, and haven't had recent chemotherapy or major surgery. They must be able to swallow pills or liquids, consent to the study, test negative for COVID-19, provide a tumor sample, undergo MRI with contrast, and have measurable disease. Pregnant women and those on certain drugs or with specific medical conditions can't participate.

Inclusion Criteria

I haven't had major surgery in the last 4 weeks and have fully recovered from any past surgeries.

I am over 18 and have a confirmed brain tumor that has come back.

Patients must have a negative COVID-19 test within 72 hours of the first dose of study drug

Exclusion Criteria

I have a heart condition that is currently causing symptoms.

I am HIV-positive and on combination anti-retroviral therapy.

Patients with alcohol or substance abuse which would interfere with compliance or safety

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Dose Escalation

Participants receive escalating doses of ONC206 to determine the maximum tolerated dose (MTD) and evaluate dose-limiting toxicities (DLTs)

28 days per cycle

Weekly visits for safety evaluation

Safety Evaluation

Safety and tolerability are monitored through physical examinations, laboratory assessments, and collection of adverse events

Ongoing throughout the trial

Every visit includes safety assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• ONC206

Trial Overview The trial is testing ONC206's safety at different doses for treating various types of recurring brain tumors. It's an early-stage study where patients take oral ONC206 either once weekly or multiple times a week to find the highest dose they can tolerate without severe side effects.

How Is the Trial Designed?

Group I: ONC206 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Jazz Pharmaceuticals

Lead Sponsor

Trials

252

Recruited

35,100+

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Chimerix

Lead Sponsor

Trials

42

Recruited

4,100+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

Oligodendrogliomas with the combined loss of chromosome arms 1p and 19q are particularly sensitive to chemotherapy, and mutations in the CIC gene are found in over 50% of these tumors, indicating a potential target for treatment.

CIC mutations lead to the upregulation of oncogenic ETV transcription factors and negative regulators of receptor tyrosine kinase signaling, suggesting that CIC-mutant oligodendrogliomas may be more aggressive than those without CIC mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ETV/Pea3 family transcription factor-encoding genes are overexpressed in CIC-mutant oligodendrogliomas. Padul, V., Epari, S., Moiyadi, A., et al.[2020]

ONC201, a drug that targets specific pathways in cancer cells, has shown promising preclinical and emerging clinical efficacy against diffuse midline gliomas (DMG), including DIPGs, which are highly lethal childhood cancers.

DIPGs with PIK3CA mutations are more sensitive to ONC201 treatment, while those with TP53 mutations are resistant; this suggests that genetic profiling could help tailor treatments, and combining ONC201 with the PI3K/Akt inhibitor paxalisib may enhance effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ONC201 in combination with paxalisib for the treatment of H3K27-altered diffuse midline glioma. Jackson, ER., Duchatel, RJ., Staudt, DE., et al.[2023]

A risk model based on three m6A-related long noncoding RNAs (lncRNAs) was identified as an independent predictor of prognosis in glioblastoma (GBM) patients, which could help in assessing patient survival and treatment outcomes.

This model is linked to the immune status and chemotherapy sensitivity in GBM, suggesting that targeting these lncRNAs may enhance immunotherapy and chemotherapy effectiveness in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RP11-552D4.1: a novel m6a-related LncRNA associated with immune status in glioblastoma. Zheng, P., Zhang, X., Ren, D., et al.[2022]

GsONC201, a locally produced version of ONC201, was confirmed to have an authentic structure and showed similar efficacy to the original ONC201 in both in vitro and in vivo studies, indicating it can be a viable treatment option for DIPG.

Patients with H3K27M-mutant DIPG treated with GsONC201 had a median overall survival of 18 months, which improved to 22 months for those who also received reirradiation, suggesting that GsONC201 may enhance survival outcomes when combined with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical and clinical evaluation of German-sourced ONC201 for the treatment of H3K27M-mutant diffuse intrinsic pontine glioma. Duchatel, RJ., Mannan, A., Woldu, AS., et al.[2022]

NUP205 is significantly overexpressed in lower-grade glioma (LGG) tissues compared to normal brain tissue, particularly in higher-grade tumors, and is associated with poorer patient survival outcomes based on an analysis of 906 samples.

The study suggests that NUP205 influences LGG progression through pathways like the cell cycle and notch signaling, and its high expression correlates with increased immune cell infiltration, especially M2 macrophages, indicating its potential as a target for immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring the relationship between abnormally high expression of NUP205 and the clinicopathological characteristics, immune microenvironment, and prognostic value of lower-grade glioma. Liang, W., Hu, C., Zhu, Q., et al.[2023]

FAM20C plays a crucial oncogenic role in gliomas by promoting cell proliferation and metastasis, as demonstrated through in vitro and in vivo studies.

Blocking FAM20C with neutralizing antibodies led to tumor regression in xenograft models, suggesting that targeting FAM20C could be a promising therapeutic strategy for glioma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epigenetic and transcriptional activation of the secretory kinase FAM20C as an oncogene in glioma. Gong, B., Liang, Y., Zhang, Q., et al.[2023]

Two cases of malignant brain tumors with BRAF V600E mutations showed promising responses to targeted treatment with BRAF and MEK inhibitors, dabrafenib and trametinib, despite previous resistance to radiation and temozolomide.

One patient had a partial response lasting 14 months, while the other maintained stable disease for 16 months, highlighting the potential of this combination therapy in treating aggressive brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent BRAF/MEK Inhibitors in BRAF V600-Mutant High-Grade Primary Brain Tumors. Schreck, KC., Guajardo, A., Lin, DDM., et al.[2019]

In a phase 1 trial involving five pediatric and young adult patients with BRAFV600-mutated brain tumors, the combination of vemurafenib (a BRAF inhibitor) and everolimus (an mTOR inhibitor) showed promising results, with 40% of patients achieving a partial response and 20% maintaining stable disease for 12 months.

No patients experienced treatment discontinuation due to adverse events, suggesting that this combination therapy is safe and warrants further investigation for treating BRAF-mutant brain cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual inhibition of BRAF and mTOR in BRAFV600E -mutant pediatric, adolescent, and young adult brain tumors. Sen, S., Tanaka, R., Khatua, S., et al.[2021]

In a study involving 25 children with newly diagnosed diffuse intrinsic pontine glioma (DIPG), the combination of vandetanib and dasatinib was found to be well tolerated, with a maximum tolerated dose of 65 mg/m² for each drug, and the most significant side effect being diarrhea.

The treatment showed promising pharmacokinetics, with the plasma levels of dasatinib remaining comparable to those seen in adults, and a decrease in phosphorylated 70S6K in blood cells, indicating effective target inhibition during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial, pharmacokinetics, and pharmacodynamics of vandetanib and dasatinib in children with newly diagnosed diffuse intrinsic pontine glioma. Broniscer, A., Baker, SD., Wetmore, C., et al.[2022]

The study found that cadherin-6 (CDH6) expression in gliomas is linked to higher tumor grades and poorer patient prognosis, suggesting it could be a significant biomarker for glioma severity.

CDH6 is primarily expressed in astrocyte-like malignant cells and is associated with immune cell infiltration in the glioma microenvironment, indicating its potential as a new therapeutic target for glioma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CDH6 as a prognostic indicator and marker for chemotherapy in gliomas. Meng, M., Zhou, H., He, Y., et al.[2022]

Citations

1. pnoc.us pnoc.us/clinical-trial/pnoc023/

PNOC023 - Clinical Trial We aim to test the tumor penetration and preliminary efficacy of ONC206 within a target validation study in children and young adults with DMGs.

2. oncotarget.com oncotarget.com/news/pr/triple-therapy-slows-glioblastoma-growth-and-extends-survival-in-preclinical-study/

Triple Therapy Slows Glioblastoma Growth and Extends ... In addition to directly killing tumor cells, ONC201 and ONC206 lowered the expression of MGMT, a protein that helps tumors resist chemotherapy, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04732065

Study Details | NCT04732065 | ONC206 for Treatment of ... ONC206 alone or in combination with radiation therapy may be effective in treating newly diagnosed or recurrent diffuse midline gliomas and other recurrent ...

4. biorxiv.org biorxiv.org/content/10.1101/2025.09.25.678693v1.full.pdf

ONC206 demonstrates potent anti-tumorigenic activity and ... Our results demonstrate that ONC206 is an effective therapeutic that warrants further clinical investigation for the treatment of children with ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11948724/

Imipridones ONC201/ONC206 + RT/TMZ triple (IRT) therapy ... Imipridones ONC201/ONC206 + RT/TMZ triple (IRT) therapy reduces intracranial tumor burden, prolongs survival in orthotopic IDH-WT GBM mouse model, and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04541082

NCT04541082 | Phase I Study of Oral ONC206 in ... The primary objective of this Phase 1, open-label, dose-escalation, and exploratory study is to evaluate the safety and tolerability profile (establish the ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04732065

ONC206 for Treatment of Newly Diagnosed, Recurrent ... This drug has been shown in laboratory experiments to kill brain tumor cells by causing a so called "stress response" in tumor cells. This stress response ...

8. humanforschung-schweiz.ch humanforschung-schweiz.ch/en/trial-search/study-detail/54254/translate/en/?cHash=4f3c60d95c114adfbfc439a915e1cebb

Assessment of the safety and efficacy of ONC206 ... Assessment of the safety and efficacy of ONC206 in children with malignant brain tumors. General information. Disease category: Other Cancer (BASEC). Study ...