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.
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.
1st recurrence only
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
Unstable angina and/or congestive heart failure requiring hospitalization
Single group
PEPIDH1M vaccine + vorasidenib
DrugPatients 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.
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
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
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