GliomaPhase 2NCT05188508
Pembrolizumab, Olaparib, and Temozolomide for People With Glioma
A Phase 2 study testing Pembrolizumab and Olaparib and Temozolomide in people with Glioma, run by Memorial Sloan Kettering Cancer Center at 10 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioma
- What is being tested?
- Pembrolizumab and Olaparib and Temozolomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 10 sitesUnited States
- Study dates
- 14 Jan 2022to Jan 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Show all 32Show fewer
- 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:
- 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
Who cannot join
- 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.
Show all 17Show fewer
- 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.
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Thomas Kaley, MD contact
10 sites in 1 country
United States10 sites, 10 recruiting
- Recruiting
Lehigh Valley Health Network (Data Collection Only)
Allentown, Pennsylvania, 18103
Tara Morrison, MD, 610-402-7880
- Recruiting
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Basking Ridge, New Jersey, 07920
Lauren Schaff, MD, 212-610-0485
- Recruiting
Memorial Sloan Kettering Suffolk -Commack (Limited Protocol Activities)
Commack, New York, 11725
Lauren Schaff, MD, 212-610-0485
- Recruiting
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Harrison, New York, 10604
Lauren Schaff, MD, 212-610-0485
- Recruiting
Hartford Healthcare Alliance (Data Collection Only)
Hartford, Connecticut, 06102
Alexis Demopoulos, MD, 860-696-5169
- Recruiting
BAPTIST ALLIANCE - MCI (Data Collection Only)
Miami, Florida, 33143
Manmeet Ahluwalia, MD, 786-613-4332
- Recruiting
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Middletown, New Jersey, 07748
Lauren Schaff, MD, 212-610-0485
- Recruiting
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Montvale, New Jersey, 07645
Lauren Schaff, MD, 212-610-0485
- Recruiting
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
New York, New York, 10065
Lauren Schaff, MD, 212-610-0485
- Recruiting
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Uniondale, New York, 11553
Lauren Schaff, MD, 212-610-0485
About this study
Official title: A Phase II Study of Pembrolizumab, Olaparib, and Temozolomide in Patients With Glioma
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
- Being tested
- Pembrolizumab, Olaparib and Temozolomide
- Keywords
- Pembrolizumab, Olaparib, Temozolomide, 20-091
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
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 TemozolomideCombination 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Pembrolizumab; Combination Product: Olaparib and Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
overall response rate (Cohort A)
The response will be determined as outlined in the RANO and iRANO.
Measured: up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2022
- Study start14 Jan 2022
- Primary completionJan 2027 (estimated)
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GliomaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 57 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Lauren Schaff, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05188508
- Sponsor's protocol ID
- 20-091
- Status last verified
- Jul 2026
- First submitted
- 27 Dec 2021
- Last updated
- 22 Jul 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Pembrolizumab, Olaparib, and Temozolomide in Patients With Glioma
- ClinicalTrials.gov ID
- NCT05188508
- Acronym / sponsor ID
- 20-091
- Conditions
- Glioma
- Keywords
- Pembrolizumab, Olaparib, Temozolomide, 20-091
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 57 participants (estimated)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 14 Jan 2022 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Jan 2027 (estimated)
- First posted
- 12 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Recurrent enhancing grade II and III IDH-mutated gliomas that have failed previous therapy | Experimental | Drug: Pembrolizumab, Combination Product: Olaparib and TemozolomideAll 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. |
| Recurrent IDH-wildtype gliomas and homologous recombination deficiency (HRD). | Experimental | Drug: Pembrolizumab, Combination Product: Olaparib and TemozolomideFive 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (32 listed)
- 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.
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabPatients will receive pembrolizumab 200mg IV on day 1 (± 3days) of each cycle. Pembrolizumab will continue every 21 days (± 3 days) throughout the trial. | Drug | 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 TemozolomideOlaparib 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. | Combination product | Recurrent IDH-wildtype gliomas and homologous recombination deficiency (HRD)., Recurrent enhancing grade II and III IDH-mutated gliomas that have failed previous therapy |
Primary outcome
overall response rate (Cohort A)
Time frame: up to 2 years
The response will be determined as outlined in the RANO and iRANO.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2026.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org
Related trials for Glioma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma
Low Grade Astrocytoma, Low Grade Glioma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Thomas Kaley, MD contact
Lauren Schaff, MD principal investigator
Memorial Sloan Kettering Cancer Center
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab and Olaparib and Temozolomide in people with Glioma, run by Memorial Sloan Kettering Cancer Center at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 32 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lauren Schaff, MD (212-610-0485, schaffl@mskcc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
overall response rate (Cohort A) (time frame: up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2026.