Vaccine + Vorasidenib for Brain Cancer

(ViCToRy Trial)

Overseen By Stevie Threatt

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Katy Peters, MD, PhD

Must not be taking: CYP3A, CYP2C9 substrates

Disqualifiers: Invasive malignancy, Metastases, AIDS, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 14 cycles of 28 days each

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates the safety and effectiveness of a new treatment that combines a vaccine called PEPIDH1M with an investigational drug named vorasidenib. It targets individuals with recurrent IDH1 mutant lower-grade gliomas, a specific type of brain cancer. The trial seeks participants who have experienced their first recurrence of this brain tumor. This research could lead to better treatment options for those facing this challenging condition. As a Phase 1 trial, it focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications that are CYP3A or CYP2C9 substrates with a narrow therapeutic index. You should switch to other medications before starting the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that using the PEPIDH1M vaccine with the drug vorasidenib might be safe and manageable for treating certain brain cancers. Vorasidenib targets specific enzymes that help tumors grow, while the vaccine strengthens the body's immune system to fight cancer cells. Studies suggest that this combination could be effective for tumors with certain mutations.

Although data from human trials remains limited, vorasidenib is already a known drug, indicating some level of safety. Early trials usually focus on safety, so researchers are likely monitoring the treatment closely for any side effects. Participants in earlier studies generally handled these treatments well, but side effects can still occur with any new therapy. Participants should discuss the possible risks and benefits with their healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of the PEPIDH1M vaccine and vorasidenib for brain cancer because it targets the IDH1 mutation, which is not addressed by current treatments like surgery, radiation, or chemotherapy. Vorasidenib works by inhibiting mutant IDH1 enzymes, potentially slowing tumor growth, while the PEPIDH1M vaccine aims to stimulate the immune system to recognize and attack cancer cells specifically with the IDH1 mutation. This dual approach offers a targeted therapy that could provide a more effective and personalized treatment option compared to the broader methods of standard care.

What evidence suggests that this trial's treatments could be effective for brain cancer?

Research has shown that vorasidenib can lower tumor 2-HG levels by 92.6%, offering promise for treating brain cancers with IDH1 mutations. Vorasidenib blocks the mutant IDH1 and IDH2 enzymes that promote cancer cell growth. In this trial, participants will receive a combination of vorasidenib and the PEPIDH1M vaccine. The PEPIDH1M vaccine targets specific genetic changes in brain cancer cells, providing a precise treatment. Early studies suggest that combining the PEPIDH1M vaccine with vorasidenib could be safe and possibly effective for recurring or worsening IDH1 mutant lower-grade gliomas. This combination aims to attack the cancer at the genetic level, potentially leading to better outcomes. ^{2 4 6 7 8}

Who Is on the Research Team?

Katherine Peters

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

Adults over 18 with a first recurrence of IDH1 mutant lower grade gliomas, who have recovered from prior treatments and have good organ function. They must not be pregnant or breastfeeding, agree to use contraception, and should not have severe medical conditions that could interfere with the trial.

Inclusion Criteria

My primary tumor tests positive for IDH1R132H.

You are expected to live for at least 12 more months.

My condition has returned only once.

Exclusion Criteria

I have been treated with mIDH1 targeted therapy before.

I have been hospitalized for heart issues recently.

Unable to undergo MRI imaging

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

A safety lead-in will be performed to assess the safety of the combination and evaluation for any dose-limiting toxicity (DLT)

4 weeks

Treatment

Patients receive vorasidenib 40 mg orally once a day for 28 days, with PEPIDH1M vaccine administered intradermally at specified intervals

14 cycles of 28 days each

Regular visits for vaccine administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

What Are the Treatments Tested in This Trial?

Interventions

• PEPIDH1M vaccine
• Vorasidenib

Trial Overview The trial is testing the combination of PEPIDH1M vaccine and vorasidenib in patients with recurrent brain tumors (lower grade gliomas). It aims to assess how safe this combo is and how well it works against these tumors.

How Is the Trial Designed?

Group I: PEPIDH1M vaccine + vorasidenib Experimental Treatment 1 Intervention

Patients will receive vaccination with 0.5 mL of Td (tetanus and diphtheria toxoids) intramuscularly into the deltoid muscle. Patients will then receive vorasidenib 40mg orally once a day for 28 days. After two cycles of 28-day vorasidenib and at the start of the 3rd cycle of vorasidenib, patients will receive the PEPIDH1M vaccine intradermally (i.d.) to alternating groin regions on the following schedule: vaccine #1, day 1; vaccine #2, day 15. The day before vaccine #1, patients will receive a vaccine site pre-conditioning injection of a single dose of Td toxoid. This will be administered twelve hours to one day prior to receiving PEPIDH1M vaccine i.d. to the RIGHT groin area. Vaccines #3 and #4 will be given on day 1 and day 15 of cycle 4. Starting on 6th cycle of 28-day vorasidenib, subjects will receive PEPIDH1M vaccine (i.d. to alternating groin regions) every 28 days on day 1 for vaccine #5-#12. Patients will receive up to a total of 14 cycles of vorasidenib.

Who Is Running the Clinical Trial?

Katy Peters, MD, PhD

Lead Sponsor

Trials

2

Recruited

70+

Servier

Industry Sponsor

Trials

55

Recruited

45,600+

Published Research Related to This Trial

Pexidartinib, a CSF-1R inhibitor, was well-tolerated in a study involving five male rhesus macaques, with no severe toxicities observed, indicating a favorable safety profile for potential CNS tumor treatment.

The study found that pexidartinib had limited penetration into the cerebrospinal fluid (CSF) after a single oral dose, suggesting that while it is safe, its effectiveness in treating CNS tumors may be compromised due to poor CNS availability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebrospinal fluid penetration of the colony-stimulating factor-1 receptor (CSF-1R) inhibitor, pexidartinib. Shankarappa, PS., Peer, CJ., Odabas, A., et al.[2021]

In a phase 3 trial involving 745 patients with newly diagnosed glioblastoma, the addition of the vaccine rindopepimut to standard chemotherapy did not significantly improve overall survival compared to the control group, with median survival times of 20.1 months versus 20.0 months, respectively.

The study was terminated for futility after an interim analysis, indicating that rindopepimut alone may not be effective in enhancing survival outcomes, suggesting that combination therapies may be necessary for immunotherapy to be effective in treating glioblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Weller, M., Butowski, N., Tran, DD., et al.[2023]

The maximum-tolerated dose (MTD) of cediranib in children with recurrent CNS tumors was initially set at 32 mg/m²/day, but excessive toxicities led to concerns about its long-term tolerability.

At a lower dose of 20 mg/m²/day, cediranib still showed poor tolerability, indicating that both doses may not be suitable for extended treatment in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial and PK study of cediranib (AZD2171), an orally bioavailable pan-VEGFR inhibitor, in children with recurrent or refractory primary CNS tumors. Kieran, MW., Chi, S., Goldman, S., et al.[2018]

In a Phase 2 study involving patients with recurrent glioblastoma, the multi-epitope long peptide vaccine TAS0313 showed an objective response rate of 11.1% and a disease control rate of 44.4%, indicating some efficacy in this challenging cancer.

TAS0313 was found to have an acceptable safety profile, with common side effects including injection site reactions and fever, but no severe adverse events or deaths reported during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the efficacy and safety of TAS0313 in adults with recurrent glioblastoma. Narita, Y., Okita, Y., Arakawa, Y.[2022]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05609994

Study Details | NCT05609994 | ViCToRy: Vorasidenib in ... This study is designed to assess the safety and efficacy of the PEPIDH1M vaccine in combination with vorasidenib in adult patients recurrent IDH1 mutant lower ...

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05609994/victory-vorasidenib-in-combination-with-tumor-specific-peptide-vaccine-for-recurrent-idh1-mutant-lower-grade-gliomas?activelyRecruiting=false&page=217&id=28&slug=brain-cancer

ViCToRy: Vorasidenib in Combination With Tumor Specific ... This study is designed to assess the safety and efficacy of the PEPIDH1M vaccine in combination with vorasidenib in adult patients recurrent ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11628568/

Vorasidenib: First Approval - PMC - PubMed Central Relative to combined data from untreated control tumors, tumor 2-HG concentrations were reduced by 92.6% (95% credible interval 76.1–97.6) in ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-04960

Vorasidenib & Peptide Vaccine for IDH1 Gliomas - NCI Giving [PEPIDH1M vaccine with vorasidenib may be safe, tolerable and/or effective in treating patients with recurrent or progressive IDH1 mutant lower grade ...

5. withpower.com withpower.com/trial/phase-1-glioma-2023-e0b22

Vaccine + Vorasidenib for Brain Cancer (ViCToRy Trial) The combination of the PEPIDH1M vaccine and Vorasidenib is unique because it targets specific genetic mutations in brain cancer cells, potentially offering a ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05609994

Study Details | NCT05609994 | ViCToRy: Vorasidenib in ... The purpose of this study is to determine the safety and efficacy of a PEPIDH1M vaccine in combination with vorasidenib, a dual inhibitor of mutant IDH1 and ...

7. reporter.nih.gov reporter.nih.gov/search/14E9CE024F8FC5D27598B8961CAA4A01A2FFCEB861BF/project-details/11178424

Project Details - NIH RePORTER Thus, we propose a clinical trial for a combined therapy of vorasidenib and PEPIDH1M. We hypothesize that early suppression of 2HG by vorasidenib would ...

8. dukecancerinstitute.org dukecancerinstitute.org/clinical-trials/victory-vorasidenib-peptide-vaccine-rlggs-lower-grade-glioma

ViCToRy: Vorasidenib + Peptide Vaccine for rLGGs (Lower ... We are doing this study to find out if the combination of an investigational peptide (small protein) vaccine developed at Duke and a drug called vorasidenib ...