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

Trial Summary

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.

What data supports the effectiveness of the treatment PEPIDH1M vaccine and Vorasidenib for brain cancer?

Research shows that Vorasidenib, a drug that targets specific mutations in brain tumors, has been tested in early trials for its ability to penetrate the brain and inhibit tumor growth. Additionally, vaccines like Rindopepimut, which target specific mutations in brain cancer cells, have shown some clinical benefits in trials, although further studies are needed to confirm their effectiveness. ^{1 2 3 4 5}

What safety data exists for the vaccine and Vorasidenib treatment for brain cancer?

The vaccine Rindopepimut, used in some studies for brain cancer, has shown minimal toxicity and is considered safe in clinical trials. No serious adverse events were reported in a study involving personalized dendritic cell vaccines for solid tumors, suggesting a favorable safety profile. ^{1 3 6 7 8}

What makes the drug combination of PEPIDH1M vaccine and Vorasidenib unique for brain cancer treatment?

The combination of the PEPIDH1M vaccine and Vorasidenib is unique because it targets specific genetic mutations in brain cancer cells, potentially offering a more personalized treatment approach compared to traditional therapies. Vorasidenib is known for its ability to inhibit mutant IDH1 and IDH2 enzymes, which are often involved in the growth of certain brain tumors, making it a novel option for patients with these mutations. ^{9 10 11 12 13}

What is the purpose of this trial?

This trial is testing a new vaccine and a daily pill to treat adults with a specific type of brain tumor that has a certain mutation. The vaccine helps the body fight the tumor, and the pill stops the tumor from growing.

Research Team

Katherine Peters

Principal Investigator

Duke University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Rindopepimut with Bevacizumab for Patients with Relapsed EGFRvIII-Expressing Glioblastoma (ReACT): Results of a Double-Blind Randomized Phase II Trial. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Vorasidenib, a Dual Inhibitor of Mutant IDH1/2, in Recurrent or Progressive Glioma; Results of a First-in-Human Phase I Trial. [2023]

3. England 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. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

Evaluation of the efficacy and safety of TAS0313 in adults with recurrent glioblastoma. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Prospect of rindopepimut in the treatment of glioblastoma. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Tumor-associated antigen-based personalized dendritic cell vaccine in solid tumor patients. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

A pilot study of peptide vaccines for VEGF receptor 1 and 2 in patients with recurrent/progressive high grade glioma. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Rindopepimut: a promising immunotherapeutic for the treatment of glioblastoma multiforme. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Cerebrospinal fluid penetration of the colony-stimulating factor-1 receptor (CSF-1R) inhibitor, pexidartinib. [2021]

10. Germany 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. [2018]

11. United States pubmed.ncbi.nlm.nih.gov

Phase I trial, pharmacokinetics, and pharmacodynamics of vandetanib and dasatinib in children with newly diagnosed diffuse intrinsic pontine glioma. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

A phase II study of the farnesyl transferase inhibitor, tipifarnib, in children with recurrent or progressive high-grade glioma, medulloblastoma/primitive neuroectodermal tumor, or brainstem glioma: a Children's Oncology Group study. [2016]

13. England pubmed.ncbi.nlm.nih.gov

An open-label study of vandetanib with pemetrexed in patients with previously treated non-small-cell lung cancer. [2022]