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Pembrolizumab and Reirradiation in Bevacizumab Naïve and Bevacizumab Resistant Recurrent Glioblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03661723
Recruitment Status : Active, not recruiting
First Posted : September 7, 2018
Results First Posted : April 7, 2023
Last Update Posted : April 26, 2024
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
David Reardon, MD, Dana-Farber Cancer Institute

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Glioblastoma
Interventions Drug: Pembrolizumab
Drug: Bevacizumab
Radiation: Re-irradiation
Enrollment 60
Recruitment Details  
Pre-assignment Details  
Arm/Group Title COH A Safety Lead-In - Dose Level 0 (200 mg Pembro Once Every 3 Weeks + 2 Weeks of RT) COH A Phase II @ RP2D (Dose Level 0: 200 mg Pembro Once Every 3 Weeks + 2 Weeks of RT) COH B Safety Lead-In - Dose Level 0 (200 mg Pembro + 15 mg/kg Bev Every 3 Weeks + 2 Weeks of RT) COH B PhII @ RP2D (Dose Level 0: 200 mg Pembro + 15 mg/kg Bev Every 3 Weeks + 2 Weeks of RT)
Hide Arm/Group Description

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.

    o Pembrolizumab is a drug (an antibody) that may treat cancer by working with the immune system

  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks o RT destroys cancer cells using radiation aimed at a cancer from a machine

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.

    o Pembrolizumab is a drug (an antibody) that may treat cancer by working with the immune system

  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks o RT destroys cancer cells using radiation aimed at a cancer from a machine

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.

    o Pembrolizumab is a drug (an antibody) that may treat cancer by working with the immune system

  • Bevacizumab or biosimilar (15 mg/kg) administered intravenously (IV) once every 3 weeks

    o Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels.

  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks o RT destroys cancer cells using radiation aimed at a cancer from a machine

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.

    o Pembrolizumab is a drug (an antibody) that may treat cancer by working with the immune system

  • Bevacizumab or biosimilar (15 mg/kg) administered intravenously (IV) once every 3 weeks

    o Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels.

  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks o RT destroys cancer cells using radiation aimed at a cancer from a machine
Period Title: Overall Study
Started 6 24 6 24
Completed 0 0 0 0
Not Completed 6 24 6 24
Reason Not Completed
Disease Progression             4             24             4             19
Withdrawal by Subject             1             0             2             4
Physician Decision             1             0             0             0
Clinical Deterioration             0             0             0             1
Arm/Group Title COH A - Dose Level 0 (200 mg Pembro Once Every 3 Weeks + 2 Weeks of RT) COH B - Dose Level 0 (200 mg Pembro + 15 mg/kg Bev Once Every 3 Weeks + 2 Weeks of RT) Total
Hide Arm/Group Description

Inclusive of both Safety Lead-In & PH II COH A participants, as they were all treated at the same dose:

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.
  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks

Inclusive of both Safety Lead-In & PH II COH B participants, as they were all treated at the same dose:

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.
  • Bevacizumab or biosimilar (15 mg/kg) administered intravenously (IV) once every 3 weeks
  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks
 Total of all reporting groups
Overall Number of Baseline Participants 30 30 60
Hide Baseline Analysis Population Description
Populations are defined by treatment assignment; Safety Lead-in and Phase II patient information is reported together
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 30 participants 60 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
26
  86.7%
22
  73.3%
48
  80.0%
>=65 years
4
  13.3%
8
  26.7%
12
  20.0%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 30 participants 30 participants 60 participants
61
(20 to 76)
61
(34 to 75)
61
(20 to 76)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 30 participants 60 participants
Female
14
  46.7%
14
  46.7%
28
  46.7%
Male
16
  53.3%
16
  53.3%
32
  53.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 30 participants 60 participants
Hispanic or Latino
1
   3.3%
5
  16.7%
6
  10.0%
Not Hispanic or Latino
26
  86.7%
17
  56.7%
43
  71.7%
Unknown or Not Reported
3
  10.0%
8
  26.7%
11
  18.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 30 participants 60 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
   3.3%
1
   1.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
1
   3.3%
1
   1.7%
White
27
  90.0%
18
  60.0%
45
  75.0%
More than one race
2
   6.7%
3
  10.0%
5
   8.3%
Unknown or Not Reported
1
   3.3%
7
  23.3%
8
  13.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 30 participants 30 participants 60 participants
30 30 60
Karnofsky performance status (KPS)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 30 participants 60 participants
KPS = 70
5
  16.7%
9
  30.0%
14
  23.3%
KPS = 80
10
  33.3%
12
  40.0%
22
  36.7%
KPS = 90
14
  46.7%
8
  26.7%
22
  36.7%
KPS = 100
1
   3.3%
1
   3.3%
2
   3.3%
[1]
Measure Description:

Karnofsky Performance Scale (KPS):

100 Normal, no complaints, no evidence of dz 90 Able to carry on normal activity; minor signs/symptoms of dz 80 Normal activity w effort; some signs/symptoms of dz 70 Cares for self, unable to carry on normal activity/do active work 60 Requires occasional assistance, but able to care for most needs 50 Requires considerable assistance & frequent medical care 40 Disabled; requires special care & assistance 30 Severely disabled; hospitalization indicated 20 Very sick; hospitalization indicated 10 Moribund; fatal processes progressing rapidly 0 Dead
Current Recurrence #  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 30 participants 60 participants
First Relapse
19
  63.3%
10
  33.3%
29
  48.3%
Second Relapse
11
  36.7%
12
  40.0%
23
  38.3%
Third Relapse
0
   0.0%
5
  16.7%
5
   8.3%
Fourth Relapse
0
   0.0%
3
  10.0%
3
   5.0%
Extent of Resection Prior to Study Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 30 participants 60 participants
Gross Total Resection (GTR)
8
  26.7%
1
   3.3%
9
  15.0%
Sub-Total Resection (STR)
6
  20.0%
0
   0.0%
6
  10.0%
Biopsy
1
   3.3%
0
   0.0%
1
   1.7%
None
11
  36.7%
29
  96.7%
40
  66.7%
Unknown
4
  13.3%
0
   0.0%
4
   6.7%
MGMT Methylation Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 30 participants 60 participants
Methylated
7
  23.3%
11
  36.7%
18
  30.0%
Unmethylated
11
  36.7%
14
  46.7%
25
  41.7%
Unknown
12
  40.0%
5
  16.7%
17
  28.3%
[1]
Measure Description: The DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) antagonizes the genotoxic effects of alkylating agents. MGMT promoter methylation is the key mechanism of MGMT gene silencing and predicts a favorable outcome in patients with glioblastoma who are exposed to alkylating agent chemotherapy.
IDH mutation  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 30 participants 60 participants
Present
2
   6.7%
3
  10.0%
5
   8.3%
Absent
17
  56.7%
26
  86.7%
43
  71.7%
Unknown
11
  36.7%
1
   3.3%
12
  20.0%
Dexamethasone Use @ Time On Study  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 30 participants 60 participants
Receiving Dexamethasone
6
  20.0%
13
  43.3%
19
  31.7%
No Dexamethasone
24
  80.0%
17
  56.7%
41
  68.3%
Time from Original GBM Diagnosis to Trial Registration  
Median (Full Range)
Unit of measure:  Months
Number Analyzed 30 participants 30 participants 60 participants
13.5
(1 to 48)
14.5
(0 to 63)
14
(0 to 63)
1.Primary Outcome
Title Objective Response Rate (ORR)
Hide Description

Per Response Assessment in Neuro-Oncology (RANO) Criteria:

  • Complete Response (CR):

    • Disappearance of all enhancing measurable & non-measurable disease sustained for at least 4 weeks
    • No new lesions
    • Stable or improved non-enhancing (T2/FLAIR) lesions
    • No corticosteroids (or physiologic replacement doses only)
    • And stable or improved clinically

  • Partial Response (PR):

    • >=50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks;
    • No progression of non-measurable disease
    • No new lesions
    • Stable or improved non-enhancing (T2/FLAIR) lesions
    • Same or lower dose of corticosteroids compared with baseline scan
    • And stable or improved clinically

Overall Response Rate (ORR) = Frequency of CR + PR within a population.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
# of participants in the analysis population who achieve a complete response (CR) or partial response (PR) using RANO criteria
Arm/Group Title COH A - Dose Level 0 (200 mg Pembro Once Every 3 Weeks + 2 Weeks of RT) COH B - Dose Level 0 (200 mg Pembro + 15 mg/kg Bev Once Every 3 Weeks + 2 Weeks of RT)
Hide Arm/Group Description:

Inclusive of both Safety Lead-In & PH II COH A participants, as they were all treated at the same dose:

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.
  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks

Inclusive of both Safety Lead-In & PH II COH B participants, as they were all treated at the same dose:

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.
  • Bevacizumab or biosimilar (15 mg/kg) administered intravenously (IV) once every 3 weeks
  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks
Overall Number of Participants Analyzed 30 30
Measure Type: Count of Participants
Unit of Measure: Participants
1
   3.3%
3
  10.0%
2.Primary Outcome
Title Overall Survival Rate at 6 Months (OS-6)
Hide Description [Not Specified]
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title COH A - Dose Level 0 (200 mg Pembro Once Every 3 Weeks + 2 Weeks of RT) COH B - Dose Level 0 (200 mg Pembro + 15 mg/kg Bev Once Every 3 Weeks + 2 Weeks of RT)
Hide Arm/Group Description:

Inclusive of both Safety Lead-In & PH II COH A participants, as they were all treated at the same dose:

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.
  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks

Inclusive of both Safety Lead-In & PH II COH B participants, as they were all treated at the same dose:

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.
  • Bevacizumab or biosimilar (15 mg/kg) administered intravenously (IV) once every 3 weeks
  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks
Overall Number of Participants Analyzed 30 30
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
83.3
(6.5 to 92.7)
56.7
(37.3 to 72.1)
3.Primary Outcome
Title Overall Survival Rate at 12 Months (OS-12)
Hide Description [Not Specified]
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title COH A - Dose Level 0 (200 mg Pembro Once Every 3 Weeks + 2 Weeks of RT) COH B - Dose Level 0 (200 mg Pembro + 15 mg/kg Bev Once Every 3 Weeks + 2 Weeks of RT)
Hide Arm/Group Description:

Inclusive of both Safety Lead-In & PH II COH A participants, as they were all treated at the same dose:

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.
  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks

Inclusive of both Safety Lead-In & PH II COH B participants, as they were all treated at the same dose:

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.
  • Bevacizumab or biosimilar (15 mg/kg) administered intravenously (IV) once every 3 weeks
  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks
Overall Number of Participants Analyzed 30 30
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
40.0
(22.8 to 56.6)
16.6
(6.0 to 31.7)
4.Secondary Outcome
Title Safety & Tolerability: SAEs Experienced by Participants
Hide Description Number of Participants who Experienced an SAE Deemed At Least Possibly Related to Study Treatment (XRT, pembrolizumab, &/or bevacizumab)
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title COH A - Dose Level 0 (200 mg Pembro Once Every 3 Weeks + 2 Weeks of RT) COH B - Dose Level 0 (200 mg Pembro + 15 mg/kg Bev Once Every 3 Weeks + 2 Weeks of RT)
Hide Arm/Group Description:

Inclusive of both Safety Lead-In & PH II COH A participants, as they were all treated at the same dose:

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.
  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks

Inclusive of both Safety Lead-In & PH II COH B participants, as they were all treated at the same dose:

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.
  • Bevacizumab or biosimilar (15 mg/kg) administered intravenously (IV) once every 3 weeks
  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks
Overall Number of Participants Analyzed 30 30
Measure Type: Count of Participants
Unit of Measure: Participants
6
  20.0%
7
  23.3%
5.Secondary Outcome
Title Duration of Response
Hide Description Each patient's response data is reviewed and the duration of his/her best response determined (in days).
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
5 COH B patients were censored for duration of response, as they each withdrew consent to be followed (or initiated a new therapy regimen) right after a scan that showed stable disease.
Arm/Group Title COH A - Dose Level 0 (200 mg Pembro Once Every 3 Weeks + 2 Weeks of RT) COH B - Dose Level 0 (200 mg Pembro + 15 mg/kg Bev Once Every 3 Weeks + 2 Weeks of RT)
Hide Arm/Group Description:

Inclusive of both Safety Lead-In & PH II COH A participants, as they were all treated at the same dose:

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.
  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks

Inclusive of both Safety Lead-In & PH II COH B participants, as they were all treated at the same dose:

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.
  • Bevacizumab or biosimilar (15 mg/kg) administered intravenously (IV) once every 3 weeks
  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks
Overall Number of Participants Analyzed 30 25
Median (Full Range)
Unit of Measure: days
79.5
(0 to 266)
42.0
(0 to 168)
6.Secondary Outcome
Title Median Progression Free Survival (PFS)
Hide Description

Progression is defined using Radiologic Assessment in Neuro-Oncology (RANO) criteria, as any of the following:

  • ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement, on stable or increasing doses of corticosteroids
  • Any new enhancing measurable lesion
  • Clear clinical deterioration not attributable to other causes apart from the tumor or changes in corticosteroid dose
  • Cohort B: Significant increase in T2/FLAIR non-enhancing lesions on stable or increasing doses of corticosteroids not felt to be caused by co-morbid events
  • Clear progression of non-measurable disease
  • Or failure to return for evaluation as a result of death or deteriorating condition
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title COH A - Dose Level 0 (200 mg Pembro Once Every 3 Weeks + 2 Weeks of RT) COH B - Dose Level 0 (200 mg Pembro + 15 mg/kg Bev Once Every 3 Weeks + 2 Weeks of RT)
Hide Arm/Group Description:

Inclusive of both Safety Lead-In & PH II COH A participants, as they were all treated at the same dose:

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.
  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks

Inclusive of both Safety Lead-In & PH II COH B participants, as they were all treated at the same dose:

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.
  • Bevacizumab or biosimilar (15 mg/kg) administered intravenously (IV) once every 3 weeks
  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks
Overall Number of Participants Analyzed 30 30
Median (Standard Error)
Unit of Measure: months
4.2  (0.4551) 4.0  (0.5467)
7.Secondary Outcome
Title 6-month Progression Free Survival (PFS-6)
Hide Description

Progression is defined using Radiologic Assessment in Neuro-Oncology (RANO) criteria, as any of the following:

  • ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement, on stable or increasing doses of corticosteroids
  • Any new enhancing measurable lesion
  • Clear clinical deterioration not attributable to other causes apart from the tumor or changes in corticosteroid dose
  • Cohort B: Significant increase in T2/FLAIR non-enhancing lesions on stable or increasing doses of corticosteroids not felt to be caused by co-morbid events
  • Clear progression of non-measurable disease
  • Or failure to return for evaluation as a result of death or deteriorating condition
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title COH A - Dose Level 0 (200 mg Pembro Once Every 3 Weeks + 2 Weeks of RT) COH B - Dose Level 0 (200 mg Pembro + 15 mg/kg Bev Once Every 3 Weeks + 2 Weeks of RT)
Hide Arm/Group Description:

Inclusive of both Safety Lead-In & PH II COH A participants, as they were all treated at the same dose:

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.
  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks

Inclusive of both Safety Lead-In & PH II COH B participants, as they were all treated at the same dose:

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.
  • Bevacizumab or biosimilar (15 mg/kg) administered intravenously (IV) once every 3 weeks
  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks
Overall Number of Participants Analyzed 30 30
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
13.3
(4.2 to 27.7)
10.6
(2.2 to 27.0)
8.Secondary Outcome
Title Median Overall Survival (OS)
Hide Description [Not Specified]
Time Frame Participants were followed for survival until death; survival was followed for a max of 4 years. Other Adverse Events (AEs) were collected from registration through 30 days after last dose (SAEs through 90 days); AEs were followed for a max of 2 years.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title COH A - Dose Level 0 (200 mg Pembro Once Every 3 Weeks + 2 Weeks of RT) COH B - Dose Level 0 (200 mg Pembro + 15 mg/kg Bev Once Every 3 Weeks + 2 Weeks of RT)
Hide Arm/Group Description:

Inclusive of both Safety Lead-In & PH II COH A participants, as they were all treated at the same dose:

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.
  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks

Inclusive of both Safety Lead-In & PH II COH B participants, as they were all treated at the same dose:

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.
  • Bevacizumab or biosimilar (15 mg/kg) administered intravenously (IV) once every 3 weeks
  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks
Overall Number of Participants Analyzed 30 30
Median (Standard Error)
Unit of Measure: months
11.8  (1.0262) 8.6  (1.1766)
Time Frame Adverse Events (AEs) were collected from registration through 30 days after last dose. Serious AEs (SAEs) were collected through 90 days after last dose (or 30 days if pt initiated new anticancer therapy). AEs were followed for a max of 2 years on this trial. Participants were followed every 3 months (+/- 1 month) until death for survival. Survival was followed for a max of 4 years on this trial.
Adverse Event Reporting Description An AE is any undesirable sign, symptom or medical condition that develops or worsens in severity after initiating study treatment or any protocol-specified procedure, regardless of attribution. An SAE is any AE at any dose & regardless of causality that: results in death, is life-threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or birth defect, or is an important medical event
 
Arm/Group Title COH A - Dose Level 0 (200 mg Pembro Once Every 3 Weeks + 2 Weeks of RT) COH B - Dose Level 0 (200 mg Pembro + 15 mg/kg Bev Once Every 3 Weeks + 2 Weeks of RT)
Hide Arm/Group Description

Inclusive of both Safety Lead-In & PH II COH A participants, as they were all treated at the same dose:

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.
  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks

Inclusive of both Safety Lead-In & PH II COH B participants, as they were all treated at the same dose:

  • Pembrolizumab (200 mg) administered intravenously (IV) once every 3 weeks.
  • Bevacizumab or biosimilar (15 mg/kg) administered intravenously (IV) once every 3 weeks
  • Re-irradiation (35 Gy) administered 5 days per week for 2 weeks
All-Cause Mortality
COH A - Dose Level 0 (200 mg Pembro Once Every 3 Weeks + 2 Weeks of RT) COH B - Dose Level 0 (200 mg Pembro + 15 mg/kg Bev Once Every 3 Weeks + 2 Weeks of RT)
Affected / at Risk (%) Affected / at Risk (%)
Total   30/30 (100.00%)   28/30 (93.33%) 
Hide Serious Adverse Events
COH A - Dose Level 0 (200 mg Pembro Once Every 3 Weeks + 2 Weeks of RT) COH B - Dose Level 0 (200 mg Pembro + 15 mg/kg Bev Once Every 3 Weeks + 2 Weeks of RT)
Affected / at Risk (%) Affected / at Risk (%)
Total   14/30 (46.67%)   11/30 (36.67%) 
Eye disorders     
Papilledema * 1  1/30 (3.33%)  0/30 (0.00%) 
Gastrointestinal disorders     
Vomiting * 1  1/30 (3.33%)  0/30 (0.00%) 
General disorders     
Fever * 1  1/30 (3.33%)  0/30 (0.00%) 
Gait disturbance * 1  1/30 (3.33%)  0/30 (0.00%) 
Infections and infestations     
Urinary tract infection * 1  1/30 (3.33%)  0/30 (0.00%) 
Sepsis * 1  0/30 (0.00%)  1/30 (3.33%) 
Injury, poisoning and procedural complications     
Fall * 1  3/30 (10.00%)  1/30 (3.33%) 
Wound complication * 1  1/30 (3.33%)  0/30 (0.00%) 
Wound dehiscence * 1  1/30 (3.33%)  0/30 (0.00%) 
Metabolism and nutrition disorders     
Hyperglycemia * 1  1/30 (3.33%)  1/30 (3.33%) 
Hyponatremia * 1  0/30 (0.00%)  1/30 (3.33%) 
Musculoskeletal and connective tissue disorders     
Generalized muscle weakness * 1  2/30 (6.67%)  1/30 (3.33%) 
Muscle weakness left-sided * 1  2/30 (6.67%)  0/30 (0.00%) 
Nervous system disorders     
Dysarthria * 1  2/30 (6.67%)  0/30 (0.00%) 
Dysphasia * 1  1/30 (3.33%)  1/30 (3.33%) 
Edema cerebral * 1  2/30 (6.67%)  2/30 (6.67%) 
Headache * 1  4/30 (13.33%)  0/30 (0.00%) 
Intracranial hemorrhage * 1  1/30 (3.33%)  1/30 (3.33%) 
Seizure * 1  1/30 (3.33%)  2/30 (6.67%) 
Stroke * 1  1/30 (3.33%)  0/30 (0.00%) 
Nervous system disorders - Other, specify: Left facial droop * 1  1/30 (3.33%)  0/30 (0.00%) 
Psychiatric disorders     
Confusion * 1  2/30 (6.67%)  2/30 (6.67%) 
Surgical and medical procedures     
Surgical and medical procedures - Other, specify: Craniotomy revision with hardware removal * 1  1/30 (3.33%)  0/30 (0.00%) 
Surgical and medical procedures - Other, specify: Craniotomy for tumor resection * 1  1/30 (3.33%)  0/30 (0.00%) 
Vascular disorders     
Thromboembolic event * 1  1/30 (3.33%)  3/30 (10.00%) 
1
Term from vocabulary, CTCAE version 4.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
COH A - Dose Level 0 (200 mg Pembro Once Every 3 Weeks + 2 Weeks of RT) COH B - Dose Level 0 (200 mg Pembro + 15 mg/kg Bev Once Every 3 Weeks + 2 Weeks of RT)
Affected / at Risk (%) Affected / at Risk (%)
Total   30/30 (100.00%)   30/30 (100.00%) 
Endocrine disorders     
Hyperthyroidism * 1  2/30 (6.67%)  0/30 (0.00%) 
Nausea * 1  2/30 (6.67%)  0/30 (0.00%) 
General disorders     
Fatigue * 1  12/30 (40.00%)  4/30 (13.33%) 
Flu like symptoms * 1  2/30 (6.67%)  0/30 (0.00%) 
Gait disturbance * 1  2/30 (6.67%)  5/30 (16.67%) 
Infections and infestations     
Sinusitis * 1  2/30 (6.67%)  0/30 (0.00%) 
Skin infection * 1  2/30 (6.67%)  0/30 (0.00%) 
Upper respiratory infection * 1  2/30 (6.67%)  0/30 (0.00%) 
Urinary tract infection * 1  3/30 (10.00%)  2/30 (6.67%) 
Injury, poisoning and procedural complications     
Fall * 1  3/30 (10.00%)  0/30 (0.00%) 
Investigations     
Alanine aminotransferase increased * 1  0/30 (0.00%)  2/30 (6.67%) 
Aspartate aminotransferase increased * 1  0/30 (0.00%)  2/30 (6.67%) 
Lymphocyte count decreased * 1  7/30 (23.33%)  3/30 (10.00%) 
Weight gain * 1  3/30 (10.00%)  0/30 (0.00%) 
Metabolism and nutrition disorders     
Anorexia * 1  0/30 (0.00%)  3/30 (10.00%) 
Hyperglycemia * 1  4/30 (13.33%)  3/30 (10.00%) 
Hypophosphatemia * 1  4/30 (13.33%)  0/30 (0.00%) 
Musculoskeletal and connective tissue disorders     
Generalized muscle weakness * 1  2/30 (6.67%)  4/30 (13.33%) 
Muscle weakness left-sided * 1  5/30 (16.67%)  0/30 (0.00%) 
Muscle weakness right-sided * 1  3/30 (10.00%)  3/30 (10.00%) 
Nervous system disorders     
Cognitive disturbance * 1  0/30 (0.00%)  2/30 (6.67%) 
Dysphasia * 1  8/30 (26.67%)  5/30 (16.67%) 
Headache * 1  10/30 (33.33%)  5/30 (16.67%) 
Memory impairment * 1  3/30 (10.00%)  2/30 (6.67%) 
Seizure * 1  2/30 (6.67%)  0/30 (0.00%) 
Psychiatric disorders     
Agitation * 1  2/30 (6.67%)  2/30 (6.67%) 
Confusion * 1  4/30 (13.33%)  0/30 (0.00%) 
Renal and urinary disorders     
Proteinuria * 1  0/30 (0.00%)  8/30 (26.67%) 
Urinary incontinence * 1  2/30 (6.67%)  3/30 (10.00%) 
Vascular disorders     
Hypertension * 1  4/30 (13.33%)  6/30 (20.00%) 
1
Term from vocabulary, CTCAE version 4.0
*
Indicates events were collected by non-systematic assessment
[Not Specified]
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: David A. Reardon, MD (Clinical Director, Center for Neuro-Oncology)
Organization: Dana-Farber Cancer Institute
Phone: 617-632-2166
EMail: david_reardon@dfci.harvard.edu
Layout table for additonal information
Responsible Party: David Reardon, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT03661723    
Other Study ID Numbers: 18-277
3475-787 ( Other Identifier: Merck )
First Submitted: September 5, 2018
First Posted: September 7, 2018
Results First Submitted: December 26, 2022
Results First Posted: April 7, 2023
Last Update Posted: April 26, 2024