GlioblastomaPhase 2NCT02337491

Pembrolizumab +/- Bevacizumab for Recurrent GBM

A Phase 2 study testing Pembrolizumab and Bevacizumab in people with Glioblastoma, run by Dana-Farber Cancer Institute at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

In this research study, the investigators are looking to determine the effectiveness of Pembrolizumab (MK-3475) when given with bevacizumab or when given alone for the treatment of recurrent glioblastoma multiforme (GBM). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Glioblastoma
What is being tested?: Pembrolizumab and Bevacizumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 80 participants
Where: 8 sitesUnited States
Study dates: 9 Feb 2015to 14 Sep 2020
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

Have histologically confirmed World Health Organization Grade IV malignant glioma (glioblastoma or gliosarcoma). Participants will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or variants is made.
Previous first line therapy with at least radiotherapy and temozolomide
Be at first or second relapse.
Participants must have shown unequivocal evidence for tumor progression by MRI or CT scan.
CT or MRI within 14 days prior to start of study drug.
An interval of at least 4 weeks (to start of study agent) between prior surgical resection or one week for stereotactic biopsy.

Show all 9Show fewer

An interval of at least 12 weeks from the completion of radiation therapy to start of study drug unless there is a new area of enhancement consistent with recurrent tumor outside the radiation field or there is unequivocal histologic confirmation of tumor progression
Participants must have recovered to grade 0 or 1 or pre-treatment baseline from clinically significant toxic effects of prior therapy (including but not limited to exceptions of alopecia, laboratory values listed per inclusion criteria, and lymphopenia which is common after therapy with temozolomide).
From the projected start of scheduled study treatment, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from antibodies, or 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies.

Who cannot join

Current or planned participation in a study of an investigational agent or using an investigational device.
Has a diagnosis of immunodeficiency.
Has tumor primarily localized to the brainstem or spinal cord.
Has presence of diffuse leptomeningeal disease or extracranial disease.
Has received systemic immunosuppressive treatments within 6 months of start of study drug
Requires treatment with high dose systemic corticosteroids defined as dexamethasone > 4 mg/day or bioequivalent for at least 3 consecutive days within 2 weeks of start of study drug.

Show all 29Show fewer

Has received prior interstitial brachytherapy, implanted chemotherapy, stereotactic radiosurgery or therapeutics delivered by local injection or convection enhanced delivery.
Requires therapeutic anticoagulation with warfarin at baseline; patients must be off warfarin or warfarin-derivative anti-coagulants for at least 7 days prior to starting study drug; however, therapeutic or prophylactic therapy with low-molecular weight heparin is allowed.
Has history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of start of study drug
Has evidence of intratumoral or peritumoral hemorrhage on baseline MRI scan other than those that are grade ≤ 1 and either post-operative or stable on at least 2 consecutive MRI scans.
Has gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE Grade > 3 within 6 months of start of study drug.
Has a known additional malignancy that is progressing or requires active treatment within 3 years of start of study drug. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
Has evidence of interstitial lung disease or 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 within the projected duration of the trial
Has a known history of HIV
Has known active Hepatitis B or Hepatitis C
Has received a live vaccine within 30 days prior to the first dose of study drug.
Has a known hypersensitivity to any of the study therapy products.
Has received anti-angiogenic or anti-VEGF targeted agents (e.g. bevacizumab, cediranib, aflibercept, vandetanib, XL-184, sunitinib, etc)
Has a history of non-healing wounds or ulcers, or bone refractures within 3 months of fracture
Has a history of arterial thromboembolism within 12 months of start of study drug.
Has inadequately controlled hypertension
Has a history of hypertensive crisis or hypertensive encephalopathy
Has had clinically significant cardiovascular disease within 12 months of start of study drug
Has a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to start of study drug.

Trial locations and contacts

8 sites in 1 country.

City, postcode or hospital

8 sites in 1 country

United States8 sites

Massachusetts General Hospital
Boston, Massachusetts, 02113
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Duke University Medical Center
Durham, North Carolina, 27710
UT, MD Anderson Cancer Center
Houston, Texas, 77030
University of California, Los Angeles
Los Angeles, California, 90095
Memorial Sloan-Kettering Cancer
New York, New York, 10021
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
University of California, San Francisco
San Francisco, California, 94143-0372

Other trials in United States

About this study

Official title: Phase II Study of Pembrolizumab (MK-3475) With and Without Bevacizumab for Recurrent Glioblastoma

Read the detailed description

Pembrolizumab (MK-3475) is a humanized monoclonal antibody. An antibody is a common type of protein made in the body in response to a foreign substance. Antibodies attack foreign substances and protect against infection. Antibodies can also be produced in the laboratory for use in treating patients, an antibody that is made in the lab is also known as a humanized monoclonal antibody. There are now several approved antibodies for the therapy of cancer and other disease. Pembrolizumab (MK-3475) has been studied in lab experiments and in other types of cancer. Information from these studies suggests that Pembrolizumab (MK-3475) may be beneficial in your type of cancer. Bevacizumab, also known as Avastin, is approved by the FDA for treating recurrent GBM. Bevacizumab is an anti-angiogenic medicine, which means it blocks blood vessels from forming that could supply the tumor with nutrients and oxygen.

There is a safety lead-in to evaluate pembrolizumab in combination of with bevacizumab (cohort A) expected to enroll up to 18 participants. Three dose levels (DL) are evaluated for pembrolizumab administered at 200 mg (flat dosing) under various dose intervals: every 3 (DL 0), 4 (DL -1) or 6 (DL -2) weeks. A standard 3+3 design is used starting at DL 0. De-escalation may occur depending on observation of dose-limiting toxicity (DLT). At least 6 participants will be evaluated for DLT at DL 0. The Phase II study randomizes participants to cohort A: pembrolizumab (using the MTD determined in the safety lead-in) and bevacizumab or cohort B: pembrolizumab monotherapy (using the MTD determined in the safety lead-in). Accrual goals are established for each cohort: A n=50 and B n=30 participants. The two cohorts are evaluated independently against a historical control and not compared. All participants treated at the safety lead-in established MTD dose level will be rolled into the Phase II cohort.

Conditions: Glioblastoma
Being tested: Pembrolizumab, Bevacizumab
Keywords: Recurrent
Medical subject headings: Glioblastoma, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PembrolizumabDrug
Also called MK-3475, SCH 900475
BevacizumabDrug
Also called Avastin

Study groups in NCT02337491
Study group	Role	What they receive
Cohort A Safety Lead-In: Pembrolizumab (DL 0) + Bevacizumab	Experimental	Pembrolizumab (Dose Level 0): 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Bevacizumab: 10 mg/kg administered Intravenously on days 1, 15 and 29 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles. Receives: Drug: Pembrolizumab
Cohort A: Pembrolizumab + Bevacizumab	Experimental	Pembrolizumab: 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Bevacizumab: 10 mg/kg administered Intravenously on days 1, 15 and 29 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles. Receives: Drug: Pembrolizumab; Drug: Bevacizumab
Cohort B: Pembrolizumab	Experimental	Pembrolizumab: 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles. Receives: Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

Pembrolizumab Maximum Tolerated Dose (MTD) [Cohort A Safety Lead-In]
The MTD of pembrolizumab in combination with bevacizumab 10 mg/kg intravenously (IV) on days 1, 15 and 29 of each 42 day cycle is determined by the number of participants who experience a dose limiting toxicity (DLT) at the various regimens of dosing frequency of pembrolizumab 200 mg IV administered under evaluation. See subsequent primary outcome measure for the DLT definition. The MTD is defined as the pembrolizumab dose frequency regimen at which fewer than one-third of participants experience a DLT. If de-escalation does not occur per design, then the starting dose is the Recommended Phase II Dose (RP2D).
Measured: one cycle/42 days
Pembrolizumab Dose Limiting Toxicity (DLT) [Cohort A Safety Lead-In]
A DLT is defined as an adverse event (AE) that (a) is >= grade 3 and related to the pembrolizumab with an attribution of possible, probably or definite, and (b) occurs during and/or begins during the first 42 days of study treatment, and (c) does not meet any of the following exception criteria: grade 3 immune-related AE that downgrades to <= grade 2 within 5 days, or <= grade 1/baseline within 14 days of onset; grade 3 asymptomatic endocrinopathy; grade 3 inflammatory reaction attribution to anti-tumor response; grade 3 pneumonitis, neurologic event, or uveitis that downgrades to <=grade 1 within 3 days; liver transaminase elevation <= 8 times institutional upper limit of normal (ULN); total bilirubin <= 5 times institutional ULN; any pre-existing lab abnormality that deteriorates to grade 3/4 and determine not clinically significant by Investigator, Overall Principal Investigator and Sponsor.
Measured: The evaluation for MTD occurred continuously through one cycle of treatment (42 days).
6-Month Progression-Free Survival (PFS6)
PFS6 is the proportion of patients remaining alive and progression-free at 6-months from study entry.
Progressive disease was established based on Response Assessment in Neuro-Oncology (RANO) criteria. PD is a >25% increase in sum of perpendicular diameters of all measurable enhancing lesions, significant increase of non-enhancing lesions, any new lesions, clear clinical deterioration, failure to return for evaluation due to death or deteriorating condition.
Measured: Disease was assessed radiographically for response every cycle on treatment. Treatment duration in cycles (cycle=42 days) was a mean (SD) of 4.5 (4.4) for Cohort A and 2.5 (2.7) for Cohort B. Assessment at week 72/cycle 12 pertains to the 6-month PFS.

Secondary outcomes (3)

Progression-Free Survival (PFS)
PFS based on Kaplan-Meier is defined as the time from study entry to the earliest documentation of disease progression (PD) or death. Participants alive without evidence of PD were censored at the date of last disease assessment. Per Response Assessment in Neuro-Oncology (RANO) criteria, PD is a >25% increase in sum of perpendicular diameters of all measurable enhancing lesions, significant increase of non-enhancing lesions, any new lesions, clear clinical deterioration, failure to return for evaluation due to death or deteriorating condition.
Measured: Disease was assessed radiographically for response every cycle on treatment and every 6 weeks long-term. Median PFS follow-up (months) was 25 for Cohort A and 26 for Cohort B.
Overall Survival (OS)
OS based on Kaplan-Meier is defined as the time from study entry to death or date last known alive.
Measured: Participants were followed long-term for survival every 3 months from the end of treatment until death or lost to follow-up. Median survival follow-up was 25 months for each cohort.
Overall Radiographic Response (ORR)
ORR was established based on Response Assessment in Neuro-Oncology (RANO) criteria. RANO criteria has 5 potential categories: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive disease (PD) and Unknown. CR: disappearance of all enhancing lesions, stable or improved non-enhancing lesions, and stable or improved clinically. PR: >= 50% decrease in sum of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, stable or improved non-enhancing lesions, and stable or improved clinically. PD: >25% increase in sum of perpendicular diameters of all measurable enhancing lesions, significant increase of non-enhancing lesions, any new lesions, clear clinical deterioration, failure to return for evaluation due to death or deteriorating condition. SD: does not qualify for CR, PR or PD.
Measured: Disease was assessed radiographically for response every cycle on treatment. Treatment duration in cycles (each cycle=42 days) was a mean (SD) of 4.5 (4.4) for Cohort A and 2.5 (2.7) for Cohort B.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

9 Feb 201514 Sep 2020

First posted13 Jan 2015 (estimated)
Study start9 Feb 2015
Primary completion28 Aug 2016
Study completion14 Sep 2020

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 (1)Papers the sponsor has linked to this study.
Other trials for GlioblastomaStudies of the same condition, open and under way.
More trials run by Dana-Farber Cancer InstituteThe 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: Randomised
Intervention model: Parallel groups
Model description: There is a safety lead-in before the start of the randomized phase 2 study.
Masking: None (open label)
Enrolment: 80 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02337491
Sponsor's protocol ID: 14-477
Status last verified: Nov 2020
First submitted: 9 Jan 2015
Last updated: 22 Dec 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

de Melo SM, Elias Nunes da Silva ME, Torloni MR, Riera R, De Cicco K, Latorraca CO, Pinto ACPN. Anti-PD-1 and anti-PD-L1 antibodies for glioma. Cochrane Database Syst Rev. 2025 Jan 8;1(1):CD012532. doi: 10.1002/14651858.CD012532.pub2.
PubMed 39777725

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 22 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase II Study of Pembrolizumab (MK-3475) With and Without Bevacizumab for Recurrent Glioblastoma
ClinicalTrials.gov ID: NCT02337491
Acronym / sponsor ID: 14-477
Conditions: Glioblastoma
Keywords: Recurrent
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 80 participants (actual)
Lead sponsor: Dana-Farber Cancer InstituteUniversity, hospital or other
Study start: 9 Feb 2015 (actual)
Primary completion: 28 Aug 2016 (actual)
Study completion: 14 Sep 2020 (actual)
First posted: 13 Jan 2015 (estimated)
Results: Posted 9 Apr 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3
Model description: There is a safety lead-in before the start of the randomized phase 2 study.

Arm	Type	Receives
Cohort A Safety Lead-In: Pembrolizumab (DL 0) + Bevacizumab	Experimental	Drug: PembrolizumabPembrolizumab (Dose Level 0): 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Bevacizumab: 10 mg/kg administered Intravenously on days 1, 15 and 29 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.
Cohort A: Pembrolizumab + Bevacizumab	Experimental	Drug: Pembrolizumab, Drug: BevacizumabPembrolizumab: 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Bevacizumab: 10 mg/kg administered Intravenously on days 1, 15 and 29 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.
Cohort B: Pembrolizumab	Experimental	Drug: PembrolizumabPembrolizumab: 200 mg administered intravenously on days 1 and 22 of each 42 day cycle Participants were treated until disease progression or unacceptable toxicity up to 16 cycles.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Have histologically confirmed World Health Organization Grade IV malignant glioma (glioblastoma or gliosarcoma). Participants will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or variants is made.
Previous first line therapy with at least radiotherapy and temozolomide
Be at first or second relapse.
Participants must have shown unequivocal evidence for tumor progression by MRI or CT scan.
CT or MRI within 14 days prior to start of study drug.

Key exclusion criteria (29 listed)

Current or planned participation in a study of an investigational agent or using an investigational device.
Has a diagnosis of immunodeficiency.
Has tumor primarily localized to the brainstem or spinal cord.
Has presence of diffuse leptomeningeal disease or extracranial disease.
Has received systemic immunosuppressive treatments within 6 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
PembrolizumabAlso: MK-3475, SCH 900475	Drug	Cohort A Safety Lead-In: Pembrolizumab (DL 0) + Bevacizumab, Cohort A: Pembrolizumab + Bevacizumab, Cohort B: Pembrolizumab
BevacizumabAlso: Avastin	Drug	Cohort A: Pembrolizumab + Bevacizumab

Primary outcome

Pembrolizumab Maximum Tolerated Dose (MTD) [Cohort A Safety Lead-In]
Time frame: one cycle/42 days
The MTD of pembrolizumab in combination with bevacizumab 10 mg/kg intravenously (IV) on days 1, 15 and 29 of each 42 day cycle is determined by the number of participants who experience a dose limiting toxicity (DLT) at the various regimens of dosing frequency of pembrolizumab 200 mg IV administered under evaluation. See subsequent primary outcome measure for the DLT definition. The MTD is defined as the pembrolizumab dose frequency regimen at which fewer than one-third of participants experience a DLT. If de-escalation does not occur per design, then the starting dose is the Recommended Phase II Dose (RP2D).
Pembrolizumab Dose Limiting Toxicity (DLT) [Cohort A Safety Lead-In]
Time frame: The evaluation for MTD occurred continuously through one cycle of treatment (42 days).
A DLT is defined as an adverse event (AE) that (a) is >= grade 3 and related to the pembrolizumab with an attribution of possible, probably or definite, and (b) occurs during and/or begins during the first 42 days of study treatment, and (c) does not meet any of the following exception criteria: grade 3 immune-related AE that downgrades to <= grade 2 within 5 days, or <= grade 1/baseline within 14 days of onset; grade 3 asymptomatic endocrinopathy; grade 3 inflammatory reaction attribution to anti-tumor response; grade 3 pneumonitis, neurologic event, or uveitis that downgrades to <=grade 1 within 3 days; liver transaminase elevation <= 8 times institutional upper limit of normal (ULN); total bilirubin <= 5 times institutional ULN; any pre-existing lab abnormality that deteriorates to grade 3/4 and determine not clinically significant by Investigator, Overall Principal Investigator and Sponsor.
6-Month Progression-Free Survival (PFS6)
Time frame: Disease was assessed radiographically for response every cycle on treatment. Treatment duration in cycles (cycle=42 days) was a mean (SD) of 4.5 (4.4) for Cohort A and 2.5 (2.7) for Cohort B. Assessment at week 72/cycle 12 pertains to the 6-month PFS.
PFS6 is the proportion of patients remaining alive and progression-free at 6-months from study entry. Progressive disease was established based on Response Assessment in Neuro-Oncology (RANO) criteria. PD is a >25% increase in sum of perpendicular diameters of all measurable enhancing lesions, significant increase of non-enhancing lesions, any new lesions, clear clinical deterioration, failure to return for evaluation due to death or deteriorating condition.

3 secondary outcomes

Progression-Free Survival (PFS)
Time frame: Disease was assessed radiographically for response every cycle on treatment and every 6 weeks long-term. Median PFS follow-up (months) was 25 for Cohort A and 26 for Cohort B.
Overall Survival (OS)
Time frame: Participants were followed long-term for survival every 3 months from the end of treatment until death or lost to follow-up. Median survival follow-up was 25 months for each cohort.
Overall Radiographic Response (ORR)
Time frame: Disease was assessed radiographically for response every cycle on treatment. Treatment duration in cycles (each cycle=42 days) was a mean (SD) of 4.5 (4.4) for Cohort A and 2.5 (2.7) for Cohort B.

Results and safety

Results posted to the registry on 9 Apr 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort A: Pembrolizumab + Bevacizumab	50	0
Cohort B: Pembrolizumab	30	0

Primary outcome: Pembrolizumab Maximum Tolerated Dose (MTD) [Cohort A Safety Lead-In]

Time frame: one cycle/42 days. Number. Unit: mg every 3 weeks

Measure	Cohort A Safety Lead-In: Pembrolizumab (DL 0) + Bevacizumab n = 6
Value	200

Population analysed: The analysis dataset is comprised of all participants who enrolled in the safety lead-in study. Only dose level 0 was evaluated and no de-escalation doses were evaluated.

Primary outcome: Pembrolizumab Dose Limiting Toxicity (DLT) [Cohort A Safety Lead-In]

Time frame: The evaluation for MTD occurred continuously through one cycle of treatment (42 days).. Number. Unit: participants with DLT

Measure	Cohort A Safety Lead-In: Pembrolizumab (DL 0) + Bevacizumab n = 6
Value	0

Population analysed: The analysis dataset is comprised of all participants who enrolled in the safety lead-in study.

Primary outcome: 6-Month Progression-Free Survival (PFS6)

Time frame: Disease was assessed radiographically for response every cycle on treatment. Treatment duration in cycles (cycle=42 days) was a mean (SD) of 4.5 (4.4) for Cohort A and 2.5 (2.7) for Cohort B. Assessment at week 72/cycle 12 pertains to the 6-month PFS.. Number (95% Confidence Interval). Unit: proportion of participants

Measure	Cohort A: Pembrolizumab + Bevacizumab n = 50	Cohort B: Pembrolizumab n = 30
Value	0.26 (0.146 to 0.403)	0.067 (0.009 to 0.221)

Population analysed: The analysis dataset is comprised of all enrolled participants.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment for unresolved AEs and up to day 90 for serious adverse events. AEs were evaluated over treatment which was a maximum duration of 16 cycles (approximates 22 months).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort A: Pembrolizumab + Bevacizumab	22 of 50 (44%)	50 of 50 (100%)	3 of 50
Cohort B: Pembrolizumab	10 of 30 (33.3%)	29 of 30 (96.7%)	1 of 30

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39777725de Melo SM, Elias Nunes da Silva ME, Torloni MR, Riera R, De Cicco K, Latorraca CO, Pinto ACPN. Anti-PD-1 and anti-PD-L1 antibodies for glioma. Cochrane Database Syst Rev. 2025 Jan 8;1(1):CD012532. doi: 10.1002/14651858.CD012532.pub2.

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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.

David Reardon, MD principal investigator

Dana-Farber Cancer Institute

8 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 Bevacizumab in people with Glioblastoma, run by Dana-Farber Cancer Institute at 8 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 9 inclusion and 29 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: finished, as of the sponsor's last update on 22 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 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 9 Apr 2018). 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?

Pembrolizumab Maximum Tolerated Dose (MTD) [Cohort A Safety Lead-In] (time frame: one cycle/42 days). 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 NCT02337491, which also lists 1 linked publication.

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 Dec 2020.