Pembrolizumab, Olaparib, and Temozolomide for People With Glioma

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• Safety Lead-In and Cohort A specific inclusion:
• Histologically confirmed grade II or III IDH-mutated glioma (absence of known CDKN2A/B deletion) that has recurred after first line therapy (consisting of at least maximum feasible surgical resection). There is no limit on the number of prior therapies or types of therapies patients can have received.
• Measurable disease by RANO criteria
• Stable dose of corticosteroids for ≥ 4 weeks prior to baseline MRI. Steroid dose not to exceed 2mg/day dexamethasone (or equivalent).
• Cohort B specific inclusion:
• Histologically confirmed IDH-wildtype glioma that has recurred following therapy (consisting of at least maximum feasible surgical resection and radiation therapy).
• Standard of care next generation sequencing via a CLIA certified platform must be available or planned and at a minimum include IDH status.
• Patient with known or suspected deleterious mutations in at least 1 of the specified 15 genes involved in homologous recombination repair (BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L)
• Measurable disease by RANO criteria
• Stable dose of corticosteroids for ≥ 4 weeks prior to baseline MRI. Steroid dose not to exceed 2mg/day dexamethasone (or equivalent).
• All Cohorts:
• Patients or their Legally Authorized Representative (LAR) must provide written informed consent prior to any screening procedures
• Age 18 or older
• ECOG 0 or 1 (KPS ≥ 70) (A lower KPS may be acceptable with prior approval from PI)
• Willing and able to comply with scheduled visits, treatment plan, and laboratory tests
• Patient must be able to swallow and retain oral medication
• Patient must have adequate organ function as defined in the following table. Stable dose of corticosteroids for ≥ 5 days prior to baseline MRI.
• Before starting study treatment, patients must have recovered to grade 1 from prior therapy (except for residual alopecia or grade 2 peripheral neuropathy).
• At least 5 half-lives must have elapsed since any prior signaling pathway modulators (e.g., EGFR, FGFR, or other tyrosine kinase inhibitors), at least 3 weeks must have elapsed since temozolomide, 4 weeks must have elapsed since carboplatin or cisplatin, and at least 6 weeks must have elapsed from nitrosoureas (e.g., BCNU, CCNU). At least 5 half-lives much have elapsed since prior IDH-inhibitor use. In general, at least 4 weeks must have elapsed from any other anticancer drug therapy (e.g. bevacizumab).
• Patients must be able to undergo contrast-enhanced MRI scans.
• Patients must have shown unequivocal evidence for tumor progression by MRI in comparison to a prior scan
• At least 12 weeks elapsed since prior radiotherapy
• Life expectancy greater than 12 weeks
• A woman of childbearing potential (WOCBP) must not have a positive urine pregnancy test within 72 hours prior to allocation.Women of reproductive potential must agree to use highly effective methods of birth control during the period of therapy and for 12 months after the last dose of the study therapy.
• Male participants must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days following the last dose of study treatment and refrain from donation sperm during this period.
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• i. Not a WOCBP or ii. A WOCBP who agrees to follow the contraceptive guidance during the treatment period for at least 120 days after the last dose of study treatment. Note: Cases of pregnancy that occur during maternal exposures to treatment should be reported. If a patient is determined to be pregnant following treatment initiation, treatment must be discontinued immediately.
• Women must agree not to breast feed while on therapy and for at least 120 days following the last dose of study drug.
• Hematological Absolute neutrophil count (ANC) ≥1500/μL Platelets ≥100 000/μL Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L
• Renal Creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels <1.5 × institutional ULN
• Hepatic Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
• Coagulation International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants

You cannot join if

• No limit on number of prior therapies
• Evidence of significant intracranial hemorrhage
• No other investigational or standard anti-tumor therapy allowed
• Patients must not have a known history of allergic reaction attributed to study drugs or compounds of similar chemical or biologic composition unless allergic reaction was managed by pre-medication.
• Patients must not have a serious pre-existing medical condition or uncontrolled intercurrent illness that would preclude participation in this study (for example, uncontrolled ventricular arrhythmia, interstitial lung disease, severe dyspnea at rest of requiring oxygen therapy, history of major surgical resection involving the stomach or bowel, or pre-existing Crohn's disease or ulcerative colitis or other autoimmune disease,) or psychiatric illness/social situations that would limit compliance with study requirements
• Patients must not have a diagnosis of immunodeficiency or be receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Patients must not have an active systemic fungal and/or known viral infection (for example human immunodeficiency virus antibodies, hepatitis B surface antigen, or hepatitis C antibodies).
• Patients must not have a history of active tuberculosis.
• Patients must not have an active infection requiring systemic therapy
• Patients must not have known history of, or any evidence of active, non-infectious pneumonitis
• Concomitant use of known strong CYP3A inhibitors (itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir)
• Concomitant use of known strong CYP3A inducers (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine, and St. John's Wort)
• A woman of childbearing potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to allocation.
• Patients must not have other active concurrent malignancy. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Patients must not have active autoimmune disease that required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment.
• Patients must not have received a live vaccine within 30 days of planned start of study (Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines are live attenuated vaccine and are not allowed)
• Concurrent treatment on another clinical trial. Supportive care trials or nontherapeutic trials (i.e. quality of life) are allowed.

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

pembrolizumab. A humanized monoclonal immunoglobulin (Ig) G4 antibody directed against human cell surface receptor PD-1 (programmed death-1 or programmed cell death-1) with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, pembrolizumab binds to PD-1, an inhibitory signaling receptor expressed on the surface of activated T cells, and blocks the binding to and activation of PD-1 by its ligands, which results in the activation of T-cell-mediated immune responses against tumor cells. The ligands for PD-1 include programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs. Activated PD-1 negatively regulates T-cell activation and plays a key role in in tumor evasion from host immunity. NCI Drug Dictionary

boron-dipyrromethene-modified olaparib fluorescent imaging agent. A poly (ADP-ribose) polymerase type 1 (PARP1) fluorescence imaging agent based on the PARP1 inhibitor olaparib, in which the cyclopropane group of olaparib is replaced by the green fluorescent dye boron-dipyrromethene (BODIPY) fluorophore (FL), with potential fluorescent imaging activity. Upon administration of the fluorescent PARP1 inhibitor PARPi-FL, the olaparib binding moiety specifically targets and binds to PARP1, which is often overexpressed on cancer cells. Upon fluorescent imaging, the PARP1-expressing cancer cells can be visualized. PARP1, the nuclear enzyme that catalyzes post-translational ADP-ribosylation of nuclear proteins, is activated by single-strand (SS) DNA breaks and overexpressed in certain tumor cells; it plays a key role in DNA repair, tumor cell resistance and survival. NCI Drug Dictionary

locally-acting temozolomide formulation SI-053. A powder for gel formulation containing the cytotoxic alkylating agent temozolomide (TMZ), an imidazotetrazine derivative of the alkylating agent dacarbazine, immobilized on the polymeric carrier dextran phosphate, with potential antineoplastic activity. The TMZ formulation SI-053 forms a viscous gel upon reconstitution in water. Upon local intraoperative administration of the gel into the cavity that is formed after resection of the brain tumor, SI-053 allows for local and prolonged action of TMZ. TMZ is converted at physiologic pH to the short-lived active compound 5-(3-methyl-(triazen-1-yl)-imidazole)-4-carboxamide (monomethyltriazenoimidazole carboxamide; MTIC). The cytotoxicity of MTIC is due to methylation of DNA, particularly at the O6 and N7 positions of guanine residues, resulting in cell cycle arrest, inhibition of DNA replication and the induction of apoptosis. The local administration of TMZ allows for the local destruction of the remaining tumor cells immediately after the removal of the tumor and may prevent the recurrence of tumor growth while having no severe systemic toxicity. NCI Drug Dictionary

Treatments listed in the registry

• Pembrolizumab (Drug): Patients will receive pembrolizumab 200mg IV on day 1 (± 3days) of each cycle. Pembrolizumab will continue every 21 days (± 3 days) throughout the trial.
• Olaparib and Temozolomide (Combination Product): Olaparib and temozolomide will begin on cycle 3 day 1 and continue through cycle 11. Olaparib will be dosed 200mg orally twice a day (bid) days 1-7 each cycle. Temozolomide 50 mg/m2 will be administered orally days 1-7 each cycle.

Non Randomized · Parallel · masking: None

Main goals

• overall response rate (Cohort A) (up to 2 years)

Planned enrollment: 57 (estimated).

• Hartford Healthcare Alliance (Data Collection Only), Hartford, Connecticut
• BAPTIST ALLIANCE - MCI (Data Collection Only), Miami, Florida
• Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities), Basking Ridge, New Jersey
• Memorial Sloan Kettering Monmouth (Limited Protocol Activities), Middletown, New Jersey
• Memorial Sloan Kettering Bergen (Limited Protocol Activities), Montvale, New Jersey
• Memorial Sloan Kettering Suffolk -Commack (Limited Protocol Activities), Commack, New York
• Memorial Sloan Kettering Westchester (Limited Protocol Activities), Harrison, New York
• Memorial Sloan Kettering Cancer Center (All Protocol Activities), New York, New York
• Memorial Sloan Kettering Nassau (Limited Protocol Activities), Uniondale, New York
• Lehigh Valley Health Network (Data Collection Only), Allentown, Pennsylvania

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT05188508
• NCI Drug Dictionary: C106432
• NCI Drug Dictionary: C71721
• NCI Drug Dictionary: C1244

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Jul 21, 2026. Public record; not medical advice.