Brain MetastasesPhase 2NCT02886585
Pembrolizumab In Central Nervous System Metastases
A Phase 2 study testing Pembrolizumab, MRI and PET/CT in people with Brain Metastases, run by Massachusetts General Hospital at 2 sites in United States.
Trial summary
This research study is studying Pembrolizumab as a possible treatment for this diagnosis for metastases in the central nervous system (brain and spinal cord). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Metastases
- What is being tested?
- Pembrolizumab, MRI and PET/CT
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 101 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2016to Jun 2028
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Participants must have histologically or cytologically confirmed disease from any solid tumor
- Participants must have measurable disease in the CNS, defined as at least one lesion that can be accurately measured in at least one dimension as ≥5 mm .
- Age ≥18 years.
- ECOG performance status ≤ 2 (Karnofsky ≥60%, see Appendix A)
- Life expectancy of greater than 6 weeks
- Participants must have normal organ and marrow function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.
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- Adequate Organ Function Laboratory Values
- Hematological
- ---- 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)
- Renal
- ---- Serum creatinine ≤1.5 X upper limit of normal (ULN)
- ----- OR
- ---- Measured or calculated a creatinine clearance ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (GFR can also be used in place of creatinine or CrCl)
- Hepatic
- ---- 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
- ----- OR
- ---- ≤ 5 X ULN for subjects with liver metastases
- Albumin >2.5 mg/dL
- Coagulation ---- 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
- Creatinine clearance should be calculated per institutional standard.
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. 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 5.7.2). 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.
- Ability to understand and the willingness to sign a written informed consent document.
- Stable dose of dexamethasone 2mg or less for 7 days prior to initiation of treatment
- Patients may have progressive systemic disease
- Patients with untreated spinal cord metastases are eligible if lesions are asymptomatic
- Patients with untreated brainstem metastases are eligible if lesions are small and asymptomatic
- Cohort Specific Eligibility Criteria
- Cohort A:
- Measurable CNS disease (one parenchymal lesion ≥5 mm)
- Previously untreated asymptomatic brain metastases
- Patients with newly diagnosed, previously untreated primary tumors that present with brain metastases should not forego available therapy that has demonstrated a definitive overall survival benefit as firstline therapy for metastatic disease; therefore, in cases of previously untreated systemic solid tumors only those patients for whom there is no available therapy with definitive overall survival benefit, those that have failed at least one line of prior therapy for their primary tumor, or those refusing standard therapy will be eligible for this study. Specifically, for patients with previously untreated primary tumors, the following diagnoses will be excluded: HER2-positive breast cancer; small cell lung cancer; NSCLC with targetable genomic tumor aberrations (e.g. EGFR, ALK).
- Cohort B:
- Measurable CNS disease (one intracranial lesion ≥5 mm)
- Progressive brain metastases after prior local CNS directed therapy such as radiation or surgery as defined by:
- Untreated measurable lesions in patients that have received surgery and/or SRS to one or more other lesions
- Residual or progressive lesions after surgery if asymptomatic
- Patients who have had prior WBRT and/or SRS and then whose lesions have progressed are eligible. Lesions treated with SRS may be eligible if there is unequivocal evidence of progression
- Cohort C:
- --- Carcinomatous meningitis, as defined by positive cytology
- Cohort D:
- Measurable CNS disease (one parenchymal lesion ≥5 mm)
- 1-4 brain metastases (where stereotactic radiosurgery would be indicated)
- Histologically confirmed diagnosis of melanoma
Who cannot join
- Participants who have had chemotherapy, targeted small molecule therapy or study therapy within 14 days of protocol treatment, or those who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 2 weeks earlier. Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- Participants who are receiving any other investigational agents.
- Has a diagnosis of immunodeficiency.
- Requires treatment with high dose systemic corticosteroids defined as dexamethasone >2mg/day or bioequivalent within 7 days of initiating therapy.
- Has received systemic immunosuppressive treatments, aside from systemic corticosteroids as described in Section 3.2.4, within three months of start of study drug
- Hypersensitivity to pembrolizumab or any of its excipients
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- Has a known history of active TB (Bacillus Tuberculosis)
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- 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.
- HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pembrolizumab. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
- 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 received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- 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.
- Unable to undergo brain MRI.
- Participants who are receiving other concurrent chemotherapies or immunotherapies for their cancer (except for patients who will receive trastuzumab, bisphosphonates, denosumab or ovarian suppression therapy Radiation therapy to a symptomatic single metastatic site or to the brain may be allowed at the investigator's discretion).
- Will need immediate local surgery or radiation for their brain metastases
- Acute symptomatic CNS hemorrhage
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
About this study
Official title: Phase II Trial of Pembrolizumab in Central Nervous System Metastases From Multiple Histologies
This research study is studying Pembrolizumab as a possible treatment for this diagnosis for metastases in the central nervous system (brain and spinal cord).
Read the detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.
Pembrolizumab may help the immune system fight cancer.
The FDA (the U.S. Food and Drug Administration) has approved pembrolizumab FDA for some diseases that are being treated on this study, but not for central nervous system metastases. Researchers hope to study the effects of pembrolizumab. Many cancers use specific pathways (such as PD-1/PD-L1 and CTLA-4) to evade the body's immune system. Pembrolizumab works by blocking the PD-1/PD-L1 pathways and thus releasing the brakes on the immune system so it can stop or slow cancer.
Researchers hope to study the effects of pembrolizumab in cancer that has metastasized to the brain. These drugs work by stimulating the immune system to fight cancer.
- Conditions
- Brain Metastases
- Being tested
- Pembrolizumab, MRI, PET/CT, Stereotactic Radiosurgery
- Keywords
- Brain Metastases
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
MRIRadiation
PET/CTRadiation
Stereotactic RadiosurgeryProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Previously Untreated Brain Metastases-Cohort A | Experimental | - Previously Untreated Brain Metastases
* Baseline Brain MRI and PET CT
* For all cohorts, pembrolizumab will be administered every 3 weeks, with 21 consecutive days defined as a treatment cycle. Treatment will be administered on an outpatient basis.
* Brain MRI and PET/CT Receives: Drug: Pembrolizumab; Radiation: MRI; Radiation: PET/CT |
| Progressive Brain Metastases-Cohort B | Experimental | - Progressive Brain Metastases
* Baseline Brain MRI and PET CT
* For all cohorts, pembrolizumab will be administered every 3 weeks, with 21 consecutive days defined as a treatment cycle. Treatment will be administered on an outpatient basis.
* Brain MRI and PET/CT Receives: Drug: Pembrolizumab; Radiation: MRI; Radiation: PET/CT |
| Neoplastic Meningitis-Cohort C | Experimental | * Neoplastic Meningitis
* Histologically confirmed solid malignancy
* Positive Cytology
* Baseline Brain MRI
* For all cohorts, pembrolizumab will be administered every 3 weeks, with 21 consecutive days defined as a treatment cycle. Treatment will be administered on an outpatient basis.
* Brain MRI and PET/CT Receives: Drug: Pembrolizumab; Radiation: MRI; Radiation: PET/CT |
| 1-4 Brain Metastases from Melanoma Cohort D | Experimental | * 1-4 Brain Metastases from Melanoma
* Clinical indication for stereostatic radiosurgery
* Evaluable extracranial focus
* For all cohorts, pembrolizumab will be administered every 3 weeks, with 21 consecutive days defined as a treatment cycle. In Cohort D, cycle 1 and 2 of pembrolizumab will be administered 3 weeks apart and stereotactic radiosurgery will be administered between cycles. Treatment will be administered on an outpatient basis.
* Brain MRI and PET CT Receives: Drug: Pembrolizumab; Radiation: MRI; Radiation: PET/CT; Procedure: Stereotactic Radiosurgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intracranial Benefit Rate (Cohorts A and B)
Contrast-enhanced cranial MRI will be performed every 6 weeks. Intracranial benefit rate is defined as the percentage of patients with complete response (CR), partial response (PR), or stable disease (SD) by RANO (Response assessment in neuro-oncology) criteria for brain metastases. CR is defined as the complete disappearance of all disease sustained for at least 4 weeks. PR is defined as greater than or equal to 30% decrease compared to baseline in the sum of target lesions sustained for at least 4 weeks and no progression of non-measurable disease. Stable disease is defined as not qualifying for CR, PR, or disease progression.
The proportion of patients in each cohort with a best response of CR or PR will be presented with a 90% confidence interval estimated using the method of Atkinson and Brown, which allows for the two-stage design.
Measured: 44 months
Overall Survival at Three Months (Cohort C)
Overall survival at three months is defined as the proportion of patients alive three months after enrollment. Any patient whose vital status is unknown due to loss of follow-up will be classified as having died for purposes of estimating the primary endpoint. The proportion of patients alive at three months will be summarized with a 90% confidence interval estimated using the method of Atkinson and Brown, which allows for the two-stage design.
Measured: 3 Months
Extracranial Overall Response Rate (Cohort D)
The proportion of patients with a best extracranial response of CR or PR will be presented with a 90% confidence interval estimated using the method of Atkinson and Brown, which allows for the two-stage design.
Measured: Data collection is ongoing for this objective. The longest time a single patient has been followed for this measure is 6 years.
Secondary outcomes (6)
Number of Participants With Grade-3 or Higher Toxicities at Least Possibly Related to Treatment (Cohorts A, B, C, D)
Toxicities were assessed per the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Measured: Up to 44 months
Median Overall Survival (Cohorts A, B, D)
Overall Survival (OS) is defined as the time from registration until death due to any cause, or censored at last date known alive.
Measured: Up to 54 months
Intracranial Response Rate (Cohort C)
Intracranial response rate is defined as the percentage of patients who achieved a complete response (CR) or partial response (PR) by RANO (Response assessment in neuro-oncology) criteria for brain metastases. CR is defined as the complete disappearance of all disease sustained for at least 4 weeks. PR is defined as greater than or equal to 30% decrease compared to baseline in the sum of target lesions sustained for at least 4 weeks and no progression of non-measurable disease.
Measured: 16 months
Extracranial Response Rate (Cohorts A and B Combined, C)
Extracranial response is defined as a complete response (CR, disappearance of all target lesions) or partial response (PR, 30% or greater decrease in the sum of diameters of target lesions in comparison with baseline) according to the Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1.
Measured: 44 months
Extracranial Progression Free Survival (Cohorts A, B, C, D)
Progression free survival (PFS) is defined as the time from registration to the earlier of disease progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation.
Measured: Up to 44 months
Intracranial Progression Free Survival (Cohorts A, B, C, D)
Progression free survival (PFS) is defined as the time from registration to the earlier of disease progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation.
Measured: Up to 44 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2016 (estimated)
- Study startOct 2016
- Primary completionJun 2027 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Brain MetastasesStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- Masking
- None (open label)
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Nancy Wang, M.D., Massachusetts General Hospital
- Investigators
- Nancy Wang, MD, MPH, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02886585
- Sponsor's protocol ID
- 16-153
- Status last verified
- Jul 2026
- First submitted
- 29 Aug 2016
- Last updated
- 21 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Brastianos PK, Kim AE, Giobbie-Hurder A, Lee EQ, Lin NU, Overmoyer B, Wen PY, Nayak L, Cohen JV, Dietrich J, Eichler A, Heist RS, Krop I, Lawrence D, Ligibel J, Tolaney S, Mayer E, Winer E, Bent B, de Sauvage MA, Ijad N, Larson JM, Marion B, Nason S, Murthy N, Ratcliff S, Summers EJ, Mahar M, Shih HA, Oh K, Cahill DP, Gerstner ER, Sullivan RJ. Pembrolizumab in brain metastases of diverse histologies: phase 2 trial results. Nat Med. 2023 Jul;29(7):1728-1737. doi: 10.1038/s41591-023-02392-7. Epub 2023 Jun 2.
PubMed 37268724Brastianos PK, Lee EQ, Cohen JV, Tolaney SM, Lin NU, Wang N, Chukwueke U, White MD, Nayyar N, Kim A, Alvarez-Breckenridge C, Krop I, Mahar MK, Bertalan MS, Shaw B, Mora JL, Goss N, Subramanian M, Nayak L, Dietrich J, Forst DA, Nahed BV, Batchelor TT, Shih HA, Gerstner ER, Moy B, Lawrence D, Giobbie-Hurder A, Carter SL, Oh K, Cahill DP, Sullivan RJ. Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. Nat Med. 2020 Aug;26(8):1280-1284. doi: 10.1038/s41591-020-0918-0. Epub 2020 Jun 2.
PubMed 32483359
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Pembrolizumab in Central Nervous System Metastases From Multiple Histologies
- ClinicalTrials.gov ID
- NCT02886585
- Acronym / sponsor ID
- 16-153
- Conditions
- Brain Metastases
- Keywords
- Brain Metastases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 101 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Oct 2016 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 1 Sep 2016 (estimated)
- Results
- Posted 26 Jun 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is studying Pembrolizumab as a possible treatment for this diagnosis for metastases in the central nervous system (brain and spinal cord).
Detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.
Pembrolizumab may help the immune system fight cancer.
The FDA (the U.S. Food and Drug Administration) has approved pembrolizumab FDA for some diseases that are being treated on this study, but not for central nervous system metastases. Researchers hope to study the effects of pembrolizumab. Many cancers use specific pathways (such as PD-1/PD-L1 and CTLA-4) to evade the body's immune system. Pembrolizumab works by blocking the PD-1/PD-L1 pathways and thus releasing the brakes on the immune system so it can stop or slow cancer.
Researchers hope to study the effects of pembrolizumab in cancer that has metastasized to the brain. These drugs work by stimulating the immune system to fight cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Previously Untreated Brain Metastases-Cohort A | Experimental | Drug: Pembrolizumab, Radiation: MRI, Radiation: PET/CT- Previously Untreated Brain Metastases * Baseline Brain MRI and PET CT * For all cohorts, pembrolizumab will be administered every 3 weeks, with 21 consecutive days defined as a treatment cycle. Treatment will be administered on an outpatient basis. * Brain MRI and PET/CT |
| Progressive Brain Metastases-Cohort B | Experimental | Drug: Pembrolizumab, Radiation: MRI, Radiation: PET/CT- Progressive Brain Metastases * Baseline Brain MRI and PET CT * For all cohorts, pembrolizumab will be administered every 3 weeks, with 21 consecutive days defined as a treatment cycle. Treatment will be administered on an outpatient basis. * Brain MRI and PET/CT |
| Neoplastic Meningitis-Cohort C | Experimental | Drug: Pembrolizumab, Radiation: MRI, Radiation: PET/CT* Neoplastic Meningitis * Histologically confirmed solid malignancy * Positive Cytology * Baseline Brain MRI * For all cohorts, pembrolizumab will be administered every 3 weeks, with 21 consecutive days defined as a treatment cycle. Treatment will be administered on an outpatient basis. * Brain MRI and PET/CT |
| 1-4 Brain Metastases from Melanoma Cohort D | Experimental | Drug: Pembrolizumab, Radiation: MRI, Radiation: PET/CT, Procedure: Stereotactic Radiosurgery* 1-4 Brain Metastases from Melanoma * Clinical indication for stereostatic radiosurgery * Evaluable extracranial focus * For all cohorts, pembrolizumab will be administered every 3 weeks, with 21 consecutive days defined as a treatment cycle. In Cohort D, cycle 1 and 2 of pembrolizumab will be administered 3 weeks apart and stereotactic radiosurgery will be administered between cycles. Treatment will be administered on an outpatient basis. * Brain MRI and PET CT |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (51 listed)
- Participants must have histologically or cytologically confirmed disease from any solid tumor
- Participants must have measurable disease in the CNS, defined as at least one lesion that can be accurately measured in at least one dimension as ≥5 mm .
- Age ≥18 years.
- ECOG performance status ≤ 2 (Karnofsky ≥60%, see Appendix A)
- Life expectancy of greater than 6 weeks
Key exclusion criteria (22 listed)
- Participants who have had chemotherapy, targeted small molecule therapy or study therapy within 14 days of protocol treatment, or those who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 2 weeks earlier. Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- Participants who are receiving any other investigational agents.
- Has a diagnosis of immunodeficiency.
- Requires treatment with high dose systemic corticosteroids defined as dexamethasone >2mg/day or bioequivalent within 7 days of initiating therapy.
- Has received systemic immunosuppressive treatments, aside from systemic corticosteroids as described in Section 3.2.4, within three months of start of study drug
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 |
|---|---|---|
| Pembrolizumab | Drug | 1-4 Brain Metastases from Melanoma Cohort D, Neoplastic Meningitis-Cohort C, Previously Untreated Brain Metastases-Cohort A, Progressive Brain Metastases-Cohort B |
| MRI | Radiation | 1-4 Brain Metastases from Melanoma Cohort D, Neoplastic Meningitis-Cohort C, Previously Untreated Brain Metastases-Cohort A, Progressive Brain Metastases-Cohort B |
| PET/CT | Radiation | 1-4 Brain Metastases from Melanoma Cohort D, Neoplastic Meningitis-Cohort C, Previously Untreated Brain Metastases-Cohort A, Progressive Brain Metastases-Cohort B |
| Stereotactic Radiosurgery | Procedure or surgery | 1-4 Brain Metastases from Melanoma Cohort D |
Primary outcome
Intracranial Benefit Rate (Cohorts A and B)
Time frame: 44 months
Contrast-enhanced cranial MRI will be performed every 6 weeks. Intracranial benefit rate is defined as the percentage of patients with complete response (CR), partial response (PR), or stable disease (SD) by RANO (Response assessment in neuro-oncology) criteria for brain metastases. CR is defined as the complete disappearance of all disease sustained for at least 4 weeks. PR is defined as greater than or equal to 30% decrease compared to baseline in the sum of target lesions sustained for at least 4 weeks and no progression of non-measurable disease. Stable disease is defined as not qualifying for CR, PR, or disease progression. The proportion of patients in each cohort with a best response of CR or PR will be presented with a 90% confidence interval estimated using the method of Atkinson and Brown, which allows for the two-stage design.
Overall Survival at Three Months (Cohort C)
Time frame: 3 Months
Overall survival at three months is defined as the proportion of patients alive three months after enrollment. Any patient whose vital status is unknown due to loss of follow-up will be classified as having died for purposes of estimating the primary endpoint. The proportion of patients alive at three months will be summarized with a 90% confidence interval estimated using the method of Atkinson and Brown, which allows for the two-stage design.
Extracranial Overall Response Rate (Cohort D)
Time frame: Data collection is ongoing for this objective. The longest time a single patient has been followed for this measure is 6 years.
The proportion of patients with a best extracranial response of CR or PR will be presented with a 90% confidence interval estimated using the method of Atkinson and Brown, which allows for the two-stage design.
6 secondary outcomes
Number of Participants With Grade-3 or Higher Toxicities at Least Possibly Related to Treatment (Cohorts A, B, C, D)
Time frame: Up to 44 months
Median Overall Survival (Cohorts A, B, D)
Time frame: Up to 54 months
Intracranial Response Rate (Cohort C)
Time frame: 16 months
Extracranial Response Rate (Cohorts A and B Combined, C)
Time frame: 44 months
Extracranial Progression Free Survival (Cohorts A, B, C, D)
Time frame: Up to 44 months
Intracranial Progression Free Survival (Cohorts A, B, C, D)
Time frame: Up to 44 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37268724Brastianos PK, Kim AE, Giobbie-Hurder A, Lee EQ, Lin NU, Overmoyer B, Wen PY, Nayak L, Cohen JV, Dietrich J, Eichler A, Heist RS, Krop I, Lawrence D, Ligibel J, Tolaney S, Mayer E, Winer E, Bent B, de Sauvage MA, Ijad N, Larson JM, Marion B, Nason S, Murthy N, Ratcliff S, Summers EJ, Mahar M, Shih HA, Oh K, Cahill DP, Gerstner ER, Sullivan RJ. Pembrolizumab in brain metastases of diverse histologies: phase 2 trial results. Nat Med. 2023 Jul;29(7):1728-1737. doi: 10.1038/s41591-023-02392-7. Epub 2023 Jun 2.
- Derived from this study: PubMed 32483359Brastianos PK, Lee EQ, Cohen JV, Tolaney SM, Lin NU, Wang N, Chukwueke U, White MD, Nayyar N, Kim A, Alvarez-Breckenridge C, Krop I, Mahar MK, Bertalan MS, Shaw B, Mora JL, Goss N, Subramanian M, Nayak L, Dietrich J, Forst DA, Nahed BV, Batchelor TT, Shih HA, Gerstner ER, Moy B, Lawrence D, Giobbie-Hurder A, Carter SL, Oh K, Cahill DP, Sullivan RJ. Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. Nat Med. 2020 Aug;26(8):1280-1284. doi: 10.1038/s41591-020-0918-0. Epub 2020 Jun 2.
- Individual participant dataSharing planned: No
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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.
Nancy Wang, MD, MPH principal investigator
Massachusetts General Hospital
2 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, MRI and PET/CT in people with Brain Metastases, run by Massachusetts General Hospital at 2 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 51 inclusion and 22 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 21 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 2 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?
Yes. Results are posted in the registry (first posted 26 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Intracranial Benefit Rate (Cohorts A and B) (time frame: 44 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02886585, which also lists 2 linked publications.
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 21 Jul 2026.