Pembrolizumab, Olaparib, and Temozolomide for People With Glioma

NCT05188508 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 20-091
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 10

Brief Summary

This study will test the safety and effectiveness of a combination of pembrolizumab, olaparib, and temozolomide to see how well these drugs work when given together in people with a glioma that either did not respond to previous treatment or came back after treatment.

Conditions

Glioma

Keywords

Pembrolizumab; Olaparib; Temozolomide; 20-091

Outcome Measures

Primary Outcomes (1)

• overall response rate (Cohort A)

  The response will be determined as outlined in the RANO and iRANO.

  up to 2 years

Study Arms (2)

Recurrent enhancing grade II and III IDH-mutated gliomas that have failed previous therapy

EXPERIMENTAL

All patients will receive pembrolizumab for two cycles prior to the addition of olaparib and temozolomide. Combination olaparib and temozolomide will be added in cycle 3. Combination therapy will continue through cycle 11 (cycles 3-11 = 27 weeks or approximately 6 months). Patients will then continue on pembrolizumab maintenance for a maximum of 35 cycles (two years) or until progression of disease or unacceptable toxicity.

Drug: Pembrolizumab; Combination Product: Olaparib and Temozolomide

Recurrent IDH-wildtype gliomas and homologous recombination deficiency (HRD).

EXPERIMENTAL

Five patients will receive pembrolizumab for two cycles prior to the addition of olaparib and temozolomide. Combination olaparib and temozolomide will be added in cycle 3. Combination therapy will continue through cycle 11 (cycles 3-11 = 27 weeks or approximately 6 months). Patients will then continue on pembrolizumab maintenance for a maximum of 35 cycles (two years) or until progression of disease or unacceptable toxicity. This cohort will be analyzed descriptively.

Drug: Pembrolizumab; Combination Product: Olaparib and Temozolomide

Interventions

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.

Recurrent IDH-wildtype gliomas and homologous recombination deficiency (HRD).; Recurrent enhancing grade II and III IDH-mutated gliomas that have failed previous therapy

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.

Recurrent IDH-wildtype gliomas and homologous recombination deficiency (HRD).; Recurrent enhancing grade II and III IDH-mutated gliomas that have failed previous therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (10)

Hartford Healthcare Alliance (Data Collection Only)

Hartford, Connecticut, 06102, United States

RECRUITING

BAPTIST ALLIANCE - MCI (Data Collection Only)

Miami, Florida, 33143, United States

RECRUITING

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Suffolk -Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

RECRUITING

Lehigh Valley Health Network (Data Collection Only)

Allentown, Pennsylvania, 18103, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Glioma

Interventions

pembrolizumab; olaparib; Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Lauren Schaff, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lauren Schaff, MD

CONTACT

212-610-0485; schaffl@mskcc.org

Thomas Kaley, MD

CONTACT

212-639-5122

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an open-label, non-randomized phase II trial of combination pembrolizumab with olaparib and temozolomide in patients with gliomas divided into two cohorts.

Study Record Dates

• First Submitted: December 27, 2021
• First Posted: January 12, 2022
• Study Start: January 14, 2022
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (10)