ViCToRy: Vorasidenib in Combination With Tumor Specific Peptide Vaccine for Recurrent IDH1 Mutant Lower Grade Gliomas

NCT05609994 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: Pro00108636
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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 IDH2 enzymes, in adult patients diagnosed with recurrent IDH1 mutant lower grade gliomas.

Conditions

Low Grade Glioma of Brain

Keywords

low grade glioma; brain cancer; vorasidenib; peptide vaccine; immunotherapy; recurrent glioma; Katherine Peters; Pro00108636; IDH mutant

Outcome Measures

Primary Outcomes (2)

• To assess the safety of the PEPIDH1M vaccine in combination vorasidenib in adult patients with progressive IDH1 mutant World Health Organization (WHO) Grade 2-3 gliomas

  The proportion of patients with an unacceptable toxicity

  3.5 years

• Describe the efficacy, as measured by progression-free survival (PFS), of the combination of PEPIDH1M vaccine and vorasidenib in adult patients with recurrent IDH1 lower grade glioma

  The time between initiation of cycle 1 vorasidenib and first documentation of disease progression or death

  10 years

Study Arms (1)

PEPIDH1M vaccine + vorasidenib

EXPERIMENTAL

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.

Drug: PEPIDH1M vaccine + vorasidenib

Interventions

PEPIDH1M vaccine + vorasidenib DRUG

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.

PEPIDH1M vaccine + vorasidenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• IDH1R132H expression in primary tumor
• Clinical and/or radiographic, progressive Grade 2-3 glioma with greater than 2 cm of non-enhancing disease in one plane.
• st recurrence only
• Signed informed consent
• For females of child-bearing potential, negative serum pregnancy test at screening
• Women of childbearing potential and male participants must agree to practice contraception
• Karnofsky Performance Status (KPS) of ≥ 70
• Expected survival of ≥ 12 months
• Recovered from any clinically relevant toxicities associated with any prior surgery for the treatment of glioma unless stabilized under medical management
• Complete Blood Count (CBC)/differential with adequate bone marrow function as defined below within 2 weeks of enrollment:
• Absolute neutrophil count (ANC) ≥ 1000 cells/mm3
• Platelet count ≥ 100,000 cells/mm3
• Hemoglobin (Hgb) ≥ 10 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 10 g/dl is acceptable.)
• Adequate renal function as defined below within 2 weeks of enrollment:

You may not qualify if:

• Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3 years (e.g., carcinoma in situ of the breast, oral cavity, and cervix are all permissible)
• Metastases detected below the tentorium or beyond the cranial vault
• More than 1 cm X 1 cm of enhancing disease on gadolinium contrasted MRI imaging
• Severe, active co-morbidity, defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization
• Myocardial infarction within the last 6 months.
• Known Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition (Note: human immunodeficiency virus \[HIV\] testing is not required for entry into this protocol. The need to exclude patients with Acquired Immunodeficiency Syndrome (AIDS) from this protocol is necessary because treatments involved in this protocol may be significantly immunosuppressive.)
• Major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.
• Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant due to study drug
• Patients with a heart-rate corrected QT interval using Fridericia's formula (QTcF) ≥ 450 msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome)
• Patients with known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Subjects with a sustained viral response to HCV treatment or immunity to prior HBV infection will be permitted (Note: Patients with chronic HBV that is adequately suppressed by institutional practice will be permitted.)
• Patients with active gastrointestinal disease, chronic diarrhea, previous gastric resection or lap band dysphagia, short-gut syndrome, gastroparesis, or other condition that limits the ingestion or gastrointestinal absorption of drugs administered orally (Note: Gastroesophageal reflux disease under medical treatment is allowed.)
• Patient taking any medications that are CYP3A or CYP2C9 substrates with a narrow therapeutic index (Note: Patients should be transferred to other medications before receiving the first dose of study drug.)
• Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study
• Patients with known hypersensitivity to GM-CSF, yeast-derived products, or any component of Leukine®

Sponsors & Collaborators

• Katy Peters, MD, PhD: lead
• Servier: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

Related Links

• The Preston Robert Tisch Brain Tumor Center at Duke
• Duke Health
• Duke Cancer Institute

MeSH Terms

Conditions

Brain Neoplasms; Glioma

Interventions

vorasidenib

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Katherine Peters, MD, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katherine Peters, MD, PhD

CONTACT

919-684-5301; dukebrain1@duke.edu

Stevie Threatt

CONTACT

919-684-5301; dukebrain1@duke.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: November 2, 2022
• First Posted: November 8, 2022
• Study Start: July 15, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2029
• Last Updated: July 18, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)