All-Trans Retinoic Acid (ATRA) Plus PD-1 Inhibition in Recurrent IDH-Mutant Glioma

Prior histopathologically proven diagnosis of astrocytoma (grade 2-4) or oligodendroglioma (grade 2-3) according to the World Health Organization (WHO) 2021 Classification System that is progressive or recurrent following at least one prior alkylating chemotherapy regimen (i.e., temozolomide and/or lomustine), +/- radiation therapy

Patient's tumor must have a known mutation in IDH1 or IDH2. IDH1/2 mutation status must be confirmed by DNA sequencing and could have been performed in any CLIA/CAP-certified laboratory. IDH1/2 mutational testing could have been performed on patient's tumor either at initial diagnosis or on a subsequent recurrent tumor.

All Safety Run-In and Phase 2 patients: patients with any contrast-enhancing tumor must have measurable disease per RANO criteria (defined by at least 1cmx1cm of contrast-enhancing tumor). Patients with exclusively non-enhancing tumors must have least a 25% increase in bi-dimensional product of FLAIR signal abnormality (measurable disease) compared to the patient's best MRI scan (smallest bi-dimensional product of FLAIR signal abnormality) obtained following completion of the patient's most recent line of therapy

Safety Run-In: Must have failed temozolomide OR another alkylator (e.g. lomustine, procarbazine, carmustine). May have failed an unlimited number of prior systemic regimens, +/- prior radiotherapy.