Study on Pembrolizumab, Olaparib, and Temozolomide for People with Glioma

Inclusion Criteria

• Have a confirmed diagnosis of grade II or III IDH-mutated glioma that has returned after initial treatment, including surgery. There is no limit on the number or types of previous treatments.
• Have a measurable tumor based on specific medical criteria.
• Be on a stable dose of corticosteroids for at least 4 weeks before the baseline MRI, with a dose not exceeding 2mg/day of dexamethasone or equivalent.
• For Cohort B: Have a confirmed diagnosis of IDH-wildtype glioma that has returned after surgery and radiation therapy.
• Have undergone or planned standard genetic testing to confirm IDH status and check for specific gene mutations related to DNA repair.
• Be 18 years or older.
• Have a performance status score indicating full activity or some restriction in strenuous activities.
• Be willing and able to attend scheduled visits, follow the treatment plan, and undergo laboratory tests.
• Be able to swallow and retain oral medication.
• Have adequate organ function based on specific blood tests.
• Have recovered from previous treatments to a certain level, except for hair loss or mild nerve damage.
• Have had enough time pass since previous cancer treatments, such as chemotherapy or radiation.
• Be able to undergo MRI scans with contrast.
• Show clear evidence of tumor progression on MRI compared to a previous scan.
• Have a life expectancy of more than 12 weeks.
• Women of childbearing potential must have a negative pregnancy test and agree to use effective birth control during and after the study.
• Men must agree to use contraception and not donate sperm during and after the study.
• Women must agree not to breastfeed during and after the study.
• Meet specific blood count and organ function criteria.

Exclusion Criteria

• No limit on the number of previous treatments.
• Have significant bleeding in the brain.
• Cannot receive other investigational or standard anti-tumor treatments.
• Have a known allergy to the study drugs unless managed with pre-medication.
• Have a serious medical condition or uncontrolled illness that would prevent participation.
• Have a diagnosis of immunodeficiency or be on high-dose steroid therapy or other immunosuppressive treatments.
• Have an active fungal or viral infection, such as HIV or hepatitis.
• Have a history of active tuberculosis.
• Have an active infection requiring treatment.
• Have a history of non-infectious lung inflammation.
• Be taking certain medications that affect drug metabolism.
• Have another active cancer, except for certain skin cancers or cervical cancer that has been treated.
• Have an active autoimmune disease requiring treatment in the past 2 years.
• Have received a live vaccine within 30 days before starting the study.
• Be participating in another clinical trial, except for supportive care or non-therapeutic trials.