Study of Vorasidenib and Pembrolizumab Combination in Recurrent or Progressive IDH-1 Mutant Glioma

Inclusion Criteria:

1. Have Karnofsky Performance Status (KPS) of ≥ 70%.

2. Have expected survival of ≥ 3 months.

3. Have histologically confirmed Grade 2 or Grade 3 glioma (per the 2016 or 2021 WorldHealth Organization [WHO] Classification of Tumors of the central nervous system)

4. Have:

5. Documented IDH1-R132H gene mutation; and

6. For Astrocytomas: Absence of 1p19q co-deletion (i.e., exclusion of combinedwhole-arm deletions of 1p and 19q) and/or documented loss of nuclear ATRXexpression or ATRX mutation by local testing. For Oligodendrogliomas: Presenceof 1p19q co-deletion (i.e., combined whole-arm deletions of 1p and 19q) bylocal testing.

7. Have measurable, magnetic resonance imaging (MRI)-evaluable, unequivocal contrastenhancing disease as determined by institutional radiologist/Investigator atScreening on either 2D T1 post-contrast weighted images or 3D T1 post-contrastweighted images. Per mRANO criteria, measurable lesion is defined as at least 1enhancing lesion measuring ≥ 1 cm x ≥ 1 cm. OR (in the absence of measurableenhancing disease) measurable, MRI-evaluable, unequivocal non enhancing disease asdetermined by institutional radiologist/Investigator at Screening on either 2D or 3DT2-weighted image or FLAIR. Per RANO 2.0 criteria, measurable lesion is defined asat least 1 non enhancing lesion measuring ≥ 1 cm × ≥ 1 cm.

8. Have recurrent or progressive disease and received prior treatment withchemotherapy, radiation, or both.

9. Surgical resection is indicated for treatment, but surgery is not urgently indicated (e.g., for whom surgery within the next 6-9 weeks is appropriate). (NOTE: Thiscriterion only applies to participants enrolled in the perioperative phase of thestudy. Participants in the Safety Lead-In should not require surgery).

Exclusion Criteria:

1. Have received prior systemic anti-cancer therapy within 1 month of the first dose ofIMP, radiation within 12 months of the first dose of IMP, or an investigationalagent < 14 days prior to the first dose of IMP. In addition, the first dose of IMPshould not occur before a period of ≥ 5 half-lives of the investigational agent haselapsed.

2. Have received 2 or more courses of radiation.

3. Have received any prior treatment with an isocitrate dehydrogenase (IDH) inhibitor;anti-programmed cell death 1 (PD1), anti-programmed cell death ligand 1 (PD-L1), oranti-PD-ligand 2 (L2) agent, or with an agent directed to another stimulatory orco-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137); any other checkpointinhibitor; bevacizumab; or any prior vaccine therapy.

Note: Other inclusion and exclusion criteria may apply.