GliomaNCT02658279
Pembrolizumab (MK-3475) in Patients With Recurrent Malignant Glioma With a Hypermutator Phenotype
A study testing Pembrolizumab in people with Glioma and Recurrent Malignant Glioma, run by Memorial Sloan Kettering Cancer Center at 16 sites in United States.
Trial summary
The purpose of this study is to test if the study drug called pembrolizumab could control the growth or shrink the cancer but it could also cause side effects. Researchers hope to learn if the study drug will shrink the cancer by half, or prevent it from growing for at least 6 months. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioma, Recurrent Malignant Glioma
- What is being tested?
- Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 16 sitesUnited States
- Study dates
- 22 Jan 2016to Jan 2027
- Phase
- Interventional
- 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
- Histologically confirmed diagnosis of malignant glioma by enrolling institution:
- WHO grade IV tumors (GBM or its variants)
- WHO grade III anaplastic astrocytoma or oligodendroglial tumors or
- WHO grade II gliomas, if MRI shows contrast enhancement
- Tumor recurrence after previous treatment, which must have included at least radiation therapy and one cytotoxic chemotherapy. There is no limit on number of previous recurrences or lines of treatment.
- Previously obtained tumor sample exhibits a hypermutator phenotype. For the purposes of this trial, a hypermutator phenotype is defined as tumors harboring 30 mutations (non-synonymous somatic point or indel mutations) detected by the MSK-IMPACT or comparable next generation sequencing performed in a CLIA environment. Contingent to approval by the MSK Principal Investigator, patients with less than 30 mutations may be eligible if they display a mutation in a mismatch repair gene or other mutations in genes known to be associated with hypermutator phenotypes or microsatellite instability, including but not limited to MLH1, MSH2, MSH6, PMS2, POLE, POLD as determined by validated methods, or if microsatellite instability is present, as identified by polymerase chain reaction (PCR) or other validated methods.
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- Note: The MSK-IMPACT (Integrated Mutation Profiling for Actionable Cancer Targets) assay is a next generation genomic profiling performed on formalin-fixed, paraffin-embedded (FFPE) tumor tissue in a CLIA-certified Molecular Diagnostic Service laboratory. IMPACT provides full exon coverage of 410 cancer related genes and can detect base substitutions, small indels, copy number alterations and selected gene re-rearrangements. In some cases, additional assays such as Sanger Sequencing or fluorescence in situ hybridization (FISH) may be required to confirm specific results detected on IMPACT. Patients at MSK will have this assay to determine eligibility. Use of other validated next-generation sequencing techniques for eligibility may be considered, provided they are performed in a CLIA-certified laboratory and are approved by the MSK Principal Investigator.
- Be willing and able to provide written informed consent/assent for the trial.
- Be ≥ 18 years of age on day of signing informed consent.
- An interval of ≥ 12 weeks from the end of prior radiation therapy is required unless there is either: i) histopathologic confirmation of recurrent tumor, or ii) new enhancement on MRI outside of the radiation treatment field
- An interval of ≥ 4 weeks after the last administration of any investigational agent or any other treatment prior to first dose of pembrolizumab
- Must have recovered (i.e., ≤ Grade 1 or at baseline) from adverse events of any previous treatment. Note: Surgical resection for recurrent tumor prior to enrollment is allowed.
- Karnofsky performance status of ≥ 70
- Demonstrate adequate organ function as per below. All screening labs should be performed within 14 days of treatment initiation.
- Absolute neutrophil count (ANC) ≥1,500 /mcL
- Platelets ≥100,000 / mcL
- Hemoglobin ≥9 g/dL or ≥ 5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
- Serum creatinine ≤1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥ 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
- Serum total bilirubin ≤ 1.5 X ULN OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
- AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN
- Albumin >2.5 mg/dL
- International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Female subject of childbearing potential should have a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 9.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
Who cannot join
- Subjects requiring escalating or chronic supraphysiologic doses of corticosteroids (> 10 mg/d of prednisone equivalent) for control of disease at the time of registration
- Previous or current treatment with an anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Hypersensitivity to pembrolizumab or any of its excipients.
- Has a diagnosis of immunodeficiency, including Human Immunodeficiency Virus (HIV) or acquired immunodeficiency syndrome (AIDS)
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has a known history of active TB (Bacillus Tuberculosis)
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- Has a known additional malignancy that is progressing or requires active treatment. 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.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e.
- with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has known history of, or any evidence of active, non-infectious pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Unable to undergo MRI of the brain (i.e. pacemaker or any other contraindication for MRIs).
- Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
- Has previously received treatment with bevacizumab
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United States16 sites
Memorial Sloan Kettering Cancer Center
Basking Ridge, New Jersey
Massachusetts General Hospital
Boston, Massachusetts, 02114
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Cleveland Clinic
Cleveland, Ohio, 44195
Memorial Sloan Kettering Commack
Commack, New York, 11725
Memorial Sloan Kettering Westchester
East White Plains, New York, 10604
Md Anderson Cancer Center
Houston, Texas, 77030
University of California, Los Angeles
Los Angeles, California, 90095
University of Miami
Miami, Florida
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of Utah
Salt Lake City, Utah, 84112
University of California San Francisco
San Francisco, California, 94143
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553
About this study
Official title: A Proof-of-Concept, Pilot Study of Pembrolizumab (MK-3475) in Patients With Recurrent Malignant Glioma With a Hypermutator Phenotype
The purpose of this study is to test if the study drug called pembrolizumab could control the growth or shrink the cancer but it could also cause side effects. Researchers hope to learn if the study drug will shrink the cancer by half, or prevent it from growing for at least 6 months. Pembrolizumab is an antibody that targets the immune system and activates it to stop cancer growth and/or kill cancer cells.
- Conditions
- Glioma, Recurrent Malignant Glioma
- Being tested
- Pembrolizumab
- Keywords
- Pembrolizumab (MK-3475), 15-227, Hypermutator Phenotype
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called (MK-3475)
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab (MK-3475) | Experimental | Pembrolizumab 200 mg will be administered as an approximately 30 minute (-5/+10 mins) IV infusion every 3 weeks. Sites should make every effort to target infusion timing to be as close to 30 minutes as possible. Patients will be followed with DCE perfusion MRI done at baseline and every 9 weeks (+/- 7 days). Patients will be allowed to stay on treatment in spite of increase in tumor size, provided the patient has no, or manageable, new neurologic symptoms, and at the discretion of treating physician. In that situation, tumor resection should be encouraged for the distinction between tumor progression and immunologic reactions. Patients undergoing surgical resection will have tissue collected for collateral studies. All collected tissue will be stored in the Pathology Core Tissue bank at MSK. Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
response rate
patients with stable disease will be considered responders if disease is stable for 27 weeks or more. The regimen will be considered worthy of further study if responses as defined above are observed in at least 3 of the 12 subjects. All subjects will undergo DCE-MRI of the head at the time points specified in Study Flow Chart . Local radiologic assessment of tumor measurements will be used during the study for clinical management and investigator-assessed disease progression. Additional MRIs may be obtained at the discretion of the investigators, as clinically indicated. Radiologic response (complete response or partial response) will be assessed by comparing on-treatment MRI scans with the pretreatment baseline MRI scans. Radiologic progression will be determined by using the smallest tumor measurement of either the pretreatment baseline or after initiation of study medication. The RANO criteria will be used for determining disease status.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2016 (estimated)
- Study start22 Jan 2016
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, M.D. Anderson Cancer Center, Dana-Farber Cancer Institute, University of California, San Francisco, Huntsman Cancer Institute, University of California, Los Angeles, University of Miami
- Responsible party
- Sponsor
- Investigators
- Thomas Kaley, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02658279
- Sponsor's protocol ID
- 15-227
- Status last verified
- Aug 2026
- First submitted
- 12 Jan 2016
- Last updated
- 20 Aug 2026
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Proof-of-Concept, Pilot Study of Pembrolizumab (MK-3475) in Patients With Recurrent Malignant Glioma With a Hypermutator Phenotype
- ClinicalTrials.gov ID
- NCT02658279
- Acronym / sponsor ID
- 15-227
- Conditions
- Glioma, Recurrent Malignant Glioma
- Keywords
- Pembrolizumab (MK-3475), 15-227, Hypermutator Phenotype
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, M.D. Anderson Cancer Center, Dana-Farber Cancer Institute, University of California, San Francisco, Huntsman Cancer Institute, University of California, Los Angeles, University of Miami
- Study start
- 22 Jan 2016 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Jan 2027 (estimated)
- First posted
- 18 Jan 2016 (estimated)
- 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.
The purpose of this study is to test if the study drug called pembrolizumab could control the growth or shrink the cancer but it could also cause side effects. Researchers hope to learn if the study drug will shrink the cancer by half, or prevent it from growing for at least 6 months. Pembrolizumab is an antibody that targets the immune system and activates it to stop cancer growth and/or kill cancer cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab (MK-3475) | Experimental | Drug: PembrolizumabPembrolizumab 200 mg will be administered as an approximately 30 minute (-5/+10 mins) IV infusion every 3 weeks. Sites should make every effort to target infusion timing to be as close to 30 minutes as possible. Patients will be followed with DCE perfusion MRI done at baseline and every 9 weeks (+/- 7 days). Patients will be allowed to stay on treatment in spite of increase in tumor size, provided the patient has no, or manageable, new neurologic symptoms, and at the discretion of treating physician. In that situation, tumor resection should be encouraged for the distinction between tumor progression and immunologic reactions. Patients undergoing surgical resection will have tissue collected for collateral studies. All collected tissue will be stored in the Pathology Core Tissue bank at MSK. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Histologically confirmed diagnosis of malignant glioma by enrolling institution:
- Tumor recurrence after previous treatment, which must have included at least radiation therapy and one cytotoxic chemotherapy. There is no limit on number of previous recurrences or lines of treatment.
- Previously obtained tumor sample exhibits a hypermutator phenotype. For the purposes of this trial, a hypermutator phenotype is defined as tumors harboring 30 mutations (non-synonymous somatic point or indel mutations) detected by the MSK-IMPACT or comparable next generation sequencing performed in a CLIA environment. Contingent to approval by the MSK Principal Investigator, patients with less than 30 mutations may be eligible if they display a mutation in a mismatch repair gene or other mutations in genes known to be associated with hypermutator phenotypes or microsatellite instability, including but not limited to MLH1, MSH2, MSH6, PMS2, POLE, POLD as determined by validated methods, or if microsatellite instability is present, as identified by polymerase chain reaction (PCR) or other validated methods.
- Note: The MSK-IMPACT (Integrated Mutation Profiling for Actionable Cancer Targets) assay is a next generation genomic profiling performed on formalin-fixed, paraffin-embedded (FFPE) tumor tissue in a CLIA-certified Molecular Diagnostic Service laboratory. IMPACT provides full exon coverage of 410 cancer related genes and can detect base substitutions, small indels, copy number alterations and selected gene re-rearrangements. In some cases, additional assays such as Sanger Sequencing or fluorescence in situ hybridization (FISH) may be required to confirm specific results detected on IMPACT. Patients at MSK will have this assay to determine eligibility. Use of other validated next-generation sequencing techniques for eligibility may be considered, provided they are performed in a CLIA-certified laboratory and are approved by the MSK Principal Investigator.
- Be willing and able to provide written informed consent/assent for the trial.
Key exclusion criteria (17 listed)
- Subjects requiring escalating or chronic supraphysiologic doses of corticosteroids (> 10 mg/d of prednisone equivalent) for control of disease at the time of registration
- Previous or current treatment with an anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Hypersensitivity to pembrolizumab or any of its excipients.
- Has a diagnosis of immunodeficiency, including Human Immunodeficiency Virus (HIV) or acquired immunodeficiency syndrome (AIDS)
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
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 |
|---|---|---|
| PembrolizumabAlso: (MK-3475) | Drug | Pembrolizumab (MK-3475) |
Primary outcome
response rate
Time frame: 1 year
patients with stable disease will be considered responders if disease is stable for 27 weeks or more. The regimen will be considered worthy of further study if responses as defined above are observed in at least 3 of the 12 subjects. All subjects will undergo DCE-MRI of the head at the time points specified in Study Flow Chart . Local radiologic assessment of tumor measurements will be used during the study for clinical management and investigator-assessed disease progression. Additional MRIs may be obtained at the discretion of the investigators, as clinically indicated. Radiologic response (complete response or partial response) will be assessed by comparing on-treatment MRI scans with the pretreatment baseline MRI scans. Radiologic progression will be determined by using the smallest tumor measurement of either the pretreatment baseline or after initiation of study medication. The RANO criteria will be used for determining disease status.
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 20 Aug 2026.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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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. This study is not recruiting at the moment.
Thomas Kaley, MD principal investigator
Memorial Sloan Kettering Cancer Center
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pembrolizumab in people with Glioma and Recurrent Malignant Glioma, run by Memorial Sloan Kettering Cancer Center at 16 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 26 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: under way, not looking for participants, as of the sponsor's last update on 20 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 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.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
response rate (time frame: 1 year). 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 20 Aug 2026.