Vorasidenib plus tumor-specific peptide vaccine for recurrent IDH1-mutant lower-grade glioma
ViCToRy: Vorasidenib in Combination With Tumor Specific Peptide Vaccine for Recurrent IDH1 Mutant Lower Grade Gliomas
This will test whether combining the oral drug vorasidenib with a tumor-specific peptide vaccine helps adults with recurrent IDH1-mutant lower-grade glioma.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 48 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Duke University Academic / other |
| Locations | 1 site (Durham, North Carolina) |
| Trial ID | NCT05609994 on ClinicalTrials.gov |
What this trial studies
This Phase 1 interventional trial gives patients vorasidenib 40 mg orally once daily in 28-day cycles alongside a PEPIDH1M intradermal peptide vaccine with a tetanus-diphtheria (Td) preconditioning injection to boost site immune response. Vaccinations are given on a defined schedule beginning after two 28-day vorasidenib cycles, then periodically through later cycles, with up to 14 total cycles of vorasidenib possible. A safety lead-in will be performed to monitor for dose-limiting toxicities before full enrollment. The study enrolls adults with confirmed IDH1 R132H recurrent grade 2–3 glioma at first recurrence and requires adequate performance status and blood counts for participation.
Who should consider this trial
Good fit: Adults (≥18) with confirmed IDH1 R132H recurrent grade 2–3 glioma at first recurrence, measurable non-enhancing disease >2 cm, KPS ≥70, adequate blood counts, and expected survival ≥12 months.
Not a fit: Patients without the IDH1 R132H mutation, with more than one prior recurrence, poor performance status, inadequate blood counts, or widespread enhancing disease are unlikely to benefit.
Why it matters
Potential benefit: If successful, the combination could generate an immune attack on IDH1-mutant tumor cells and slow tumor growth, potentially prolonging progression-free survival.
How similar studies have performed: Early-phase trials of IDH1-targeted peptide vaccines and of IDH inhibitors such as vorasidenib have shown safety and immune or radiographic activity separately, but combining them is a novel approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
1. Age ≥ 18 years
2. IDH1R132H expression in primary tumor
3. Clinical and/or radiographic, progressive Grade 2-3 glioma with greater than 2 cm of non-enhancing disease in one plane.
4. 1st recurrence only
5. Signed informed consent
6. For females of child-bearing potential, negative serum pregnancy test at screening
7. Women of childbearing potential and male participants must agree to practice contraception
8. Karnofsky Performance Status (KPS) of ≥ 70
9. Expected survival of ≥ 12 months
10. Recovered from any clinically relevant toxicities associated with any prior surgery for the treatment of glioma unless stabilized under medical management
11. Complete Blood Count (CBC)/differential with adequate bone marrow function as defined below within 2 weeks of enrollment:
1. Absolute neutrophil count (ANC) ≥ 1000 cells/mm3
2. Platelet count ≥ 100,000 cells/mm3
3. Hemoglobin (Hgb) ≥ 10 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 10 g/dl is acceptable.)
12. Adequate renal function as defined below within 2 weeks of enrollment:
1. Blood urea nitrogen (BUN) ≤ 25 mg/dl
2. Creatinine ≤ 1.7 mg/dl
13. Adequate hepatic function as defined below within 2 weeks of enrollment:
1. Bilirubin ≤ 2.0 mg/dl
2. Alanine transaminase (ALT) ≤ 3 x normal range
3. Aspartate aminotransferase (AST) ≤ 3 x normal range
Exclusion Criteria:
1. 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)
2. Metastases detected below the tentorium or beyond the cranial vault
3. More than 1 cm X 1 cm of enhancing disease on gadolinium contrasted MRI imaging
4. Severe, active co-morbidity, defined as follows:
1. Unstable angina and/or congestive heart failure requiring hospitalization
2. Myocardial infarction within the last 6 months.
3. 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.)
4. Major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.
5. Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant due to study drug
6. 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)
7. 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.)
8. 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.)
9. 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.)
10. Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study
11. Patients with known hypersensitivity to GM-CSF, yeast-derived products, or any component of Leukine®
12. Allergy or hypersensitivity to tetanus vaccine or any component of the tetanus vaccine.
13. Known hypersensitivity to any component of vorasidenib
14. Prior therapy with mIDH1 targeted therapeutics
15. Unable to undergo MRI imaging
Where this trial is running
Durham, North Carolina
- Duke University Medical Center — Durham, North Carolina, United States (Recruiting)
Study contacts
- Principal investigator: Katherine Peters, MD, PhD — Duke University
- Study coordinator: Katherine Peters, MD, PhD
- Email: dukebrain1@duke.edu
- Phone: 919-684-5301
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.