Trial Outcomes & Findings for Pembrolizumab Plus Bevacizumab for Treatment of Brain Metastases in Metastatic Melanoma or Non-small Cell Lung Cancer (NSCLC) (NCT NCT02681549)
NCT ID: NCT02681549
Last Updated: 2025-08-07
Results Overview
Brain metastasis response rate (BMRR) using modified RECIST (mRECIST) criteria
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
41 participants
Primary outcome timeframe
up to 2 years from start of treatment
Results posted on
2025-08-07
Participant Flow
Participant milestones
| Measure |
Untreated Brain Metastases From Melanoma
pembrolizumab plus bevacizumab
Pembrolizumab plus Bevacizumab: Pembrolizumab will be administered on day 1 of every cycle until disease progression or withdrawal from study. Bevacizumab will be administered in addition to pembrolizumab on day 1 of cycles 1, 2, 3, and 4 (or alternative cycles if bevacizumab is held during these cycles). Three weeks constitutes one cycle.
|
Untreated Brain Metastases From NSCLC
pembrolizumab plus bevacizumab
Pembrolizumab plus Bevacizumab: Pembrolizumab will be administered on day 1 of every cycle until disease progression or withdrawal from study. Bevacizumab will be administered in addition to pembrolizumab on day 1 of cycles 1, 2, 3, and 4 (or alternative cycles if bevacizumab is held during these cycles). Three weeks constitutes one cycle.
|
|---|---|---|
|
Overall Study
STARTED
|
37
|
4
|
|
Overall Study
COMPLETED
|
37
|
2
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
This measure does not apply to NSCLC group.
Baseline characteristics by cohort
| Measure |
Untreated Brain Metastases From Melanoma
n=37 Participants
pembrolizumab plus bevacizumab
|
Untreated Brain Metastases From NSCLC
n=4 Participants
pembrolizumab plus bevacizumab
|
Total
n=41 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
66 years
n=37 Participants
|
67 years
n=4 Participants
|
66 years
n=41 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=37 Participants
|
3 Participants
n=4 Participants
|
13 Participants
n=41 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=37 Participants
|
1 Participants
n=4 Participants
|
28 Participants
n=41 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=37 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=41 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
34 Participants
n=37 Participants
|
3 Participants
n=4 Participants
|
37 Participants
n=41 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=37 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=41 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=37 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=41 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=37 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=41 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=37 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=41 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=37 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=41 Participants
|
|
Race (NIH/OMB)
White
|
36 Participants
n=37 Participants
|
3 Participants
n=4 Participants
|
39 Participants
n=41 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=37 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=41 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=37 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=41 Participants
|
|
Region of Enrollment
United States
|
37 participants
n=37 Participants
|
5 participants
n=4 Participants
|
42 participants
n=41 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) performance status
0
|
25 units on a scale
n=37 Participants
|
1 units on a scale
n=4 Participants
|
26 units on a scale
n=41 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) performance status
1
|
12 units on a scale
n=37 Participants
|
4 units on a scale
n=4 Participants
|
16 units on a scale
n=41 Participants
|
|
Mutation Status
BRAF WT
|
19 participants
n=37 Participants • This measure does not apply to NSCLC group.
|
—
|
19 participants
n=37 Participants • This measure does not apply to NSCLC group.
|
|
Mutation Status
BRAF Mutant
|
16 participants
n=37 Participants • This measure does not apply to NSCLC group.
|
—
|
16 participants
n=37 Participants • This measure does not apply to NSCLC group.
|
|
Mutation Status
V600E
|
9 participants
n=37 Participants • This measure does not apply to NSCLC group.
|
—
|
9 participants
n=37 Participants • This measure does not apply to NSCLC group.
|
|
Mutation Status
V600K
|
6 participants
n=37 Participants • This measure does not apply to NSCLC group.
|
—
|
6 participants
n=37 Participants • This measure does not apply to NSCLC group.
|
|
Mutation Status
Unknown V600 type
|
1 participants
n=37 Participants • This measure does not apply to NSCLC group.
|
—
|
1 participants
n=37 Participants • This measure does not apply to NSCLC group.
|
|
Mutation Status
NRAS Mutant
|
4 participants
n=37 Participants • This measure does not apply to NSCLC group.
|
—
|
4 participants
n=37 Participants • This measure does not apply to NSCLC group.
|
|
Mutation Status
Unknown Mutation Status
|
2 participants
n=37 Participants • This measure does not apply to NSCLC group.
|
—
|
2 participants
n=37 Participants • This measure does not apply to NSCLC group.
|
|
Serum lactate dehydrogenase
Normal levels
|
25 Participants
n=37 Participants • This measure does not apply to NSCLC group.
|
0 Participants
This measure does not apply to NSCLC group.
|
25 Participants
n=37 Participants • This measure does not apply to NSCLC group.
|
|
Serum lactate dehydrogenase
Elevated levels
|
12 Participants
n=37 Participants • This measure does not apply to NSCLC group.
|
0 Participants
This measure does not apply to NSCLC group.
|
12 Participants
n=37 Participants • This measure does not apply to NSCLC group.
|
|
Number of intracranial target lesions
1-2
|
23 Participants
n=37 Participants
|
4 Participants
n=4 Participants
|
27 Participants
n=41 Participants
|
|
Number of intracranial target lesions
3-5
|
14 Participants
n=37 Participants
|
0 Participants
n=4 Participants
|
14 Participants
n=41 Participants
|
|
Presence of extracranial metastases
Yes
|
32 Participants
n=37 Participants
|
4 Participants
n=4 Participants
|
36 Participants
n=41 Participants
|
|
Presence of extracranial metastases
No
|
5 Participants
n=37 Participants
|
0 Participants
n=4 Participants
|
5 Participants
n=41 Participants
|
|
Prior systemic therapy
Yes
|
7 Participants
n=37 Participants
|
0 Participants
n=4 Participants
|
7 Participants
n=41 Participants
|
|
Prior systemic therapy
No
|
30 Participants
n=37 Participants
|
4 Participants
n=4 Participants
|
34 Participants
n=41 Participants
|
|
Prior local therapy for MBM
Yes
|
19 Participants
n=37 Participants
|
2 Participants
n=4 Participants
|
21 Participants
n=41 Participants
|
|
Prior local therapy for MBM
No
|
18 Participants
n=37 Participants
|
3 Participants
n=4 Participants
|
21 Participants
n=41 Participants
|
PRIMARY outcome
Timeframe: up to 2 years from start of treatmentBrain metastasis response rate (BMRR) using modified RECIST (mRECIST) criteria
Outcome measures
| Measure |
Untreated Brain Metastases From Melanoma
n=37 Participants
pembrolizumab plus bevacizumab
|
Untreated Brain Metastases From NSCLC
n=4 Participants
pembrolizumab plus bevacizumab
|
|---|---|---|
|
Brain Metastasis Response Rate (BMRR)
|
54.1 percentage of participants
|
75 percentage of participants
|
SECONDARY outcome
Timeframe: up to 2 years from start of treatmentPopulation: At time of analysis it was found that data reported by participants was incorrect and could not be used.
Number of patients using steroids to control of cerebral edema for greater than 96 hours
Outcome measures
| Measure |
Untreated Brain Metastases From Melanoma
n=37 Participants
pembrolizumab plus bevacizumab
|
Untreated Brain Metastases From NSCLC
n=4 Participants
pembrolizumab plus bevacizumab
|
|---|---|---|
|
Steroid Use
|
3 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: up to 2 years from start of treatmentPopulation: Denominator for extracranial response is 32 because 5 patients did not have extracranial metastases at baseline
best overall response rate (ORR) by mRECIST criteria in the brain or RECIST criteria in the body
Outcome measures
| Measure |
Untreated Brain Metastases From Melanoma
n=37 Participants
pembrolizumab plus bevacizumab
|
Untreated Brain Metastases From NSCLC
n=4 Participants
pembrolizumab plus bevacizumab
|
|---|---|---|
|
Overall Response Rate (ORR)
Intracranial
|
54.1 percentage of participants
|
75 percentage of participants
|
|
Overall Response Rate (ORR)
Extracranial
|
56.3 percentage of participants
|
75 percentage of participants
|
SECONDARY outcome
Timeframe: up to 9 years from start of treatment or to disease progressionProgression-free survival by mRECIST criteria in the brain or RECIST criteria in the body
Outcome measures
| Measure |
Untreated Brain Metastases From Melanoma
n=37 Participants
pembrolizumab plus bevacizumab
|
Untreated Brain Metastases From NSCLC
n=4 Participants
pembrolizumab plus bevacizumab
|
|---|---|---|
|
Progression-free Survival (PFS)
Median overall PFS
|
1.2 years
Interval 0.23 to
Due to small sample size and censoring, upper limit could not be calculated
|
NA years
Due to small sample size and censoring, PFS could not be calculated
|
|
Progression-free Survival (PFS)
Median intracranial PFS
|
2.2 years
Interval 0.41 to
Due to small sample size and censoring, upper limit could not be calculated
|
NA years
Due to small sample size and censoring, PFS could not be calculated
|
SECONDARY outcome
Timeframe: up to 2 years from start of treatmentNumber of participants that experienced at least 1 treatment related adverse event.
Outcome measures
| Measure |
Untreated Brain Metastases From Melanoma
n=37 Participants
pembrolizumab plus bevacizumab
|
Untreated Brain Metastases From NSCLC
n=4 Participants
pembrolizumab plus bevacizumab
|
|---|---|---|
|
Safety and Toxicity of Combination Pembrolizumab and Bevacizumab Assessed Using Common Terminology Criteria for Adverse Events v. 4.
|
32 Participants
|
3 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 2 years from start of trialOutcome measures
Outcome data not reported
Adverse Events
Untreated Brain Metastases From Melanoma
Serious events: 4 serious events
Other events: 27 other events
Deaths: 1 deaths
Untreated Brain Metastases From NSCLC
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Untreated Brain Metastases From Melanoma
n=37 participants at risk
pembrolizumab plus bevacizumab
|
Untreated Brain Metastases From NSCLC
n=5 participants at risk
pembrolizumab plus bevacizumab
|
|---|---|---|
|
Investigations
Investigations - Other, specify
|
5.4%
2/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Endocrine disorders
Hypophysitis
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Vascular disorders
Wound dehiscence and infection
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Cardiac disorders
Pericardial tamponade
|
0.00%
0/37 • up to 2 years from the start of treatment
|
20.0%
1/5 • up to 2 years from the start of treatment
|
Other adverse events
| Measure |
Untreated Brain Metastases From Melanoma
n=37 participants at risk
pembrolizumab plus bevacizumab
|
Untreated Brain Metastases From NSCLC
n=5 participants at risk
pembrolizumab plus bevacizumab
|
|---|---|---|
|
General disorders
Fatigue
|
24.3%
9/37 • up to 2 years from the start of treatment
|
20.0%
1/5 • up to 2 years from the start of treatment
|
|
Skin and subcutaneous tissue disorders
Rash
|
21.6%
8/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Musculoskeletal and connective tissue disorders
Arthralgias
|
18.9%
7/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Investigations
Investigations - Other, specify
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/37 • up to 2 years from the start of treatment
|
20.0%
1/5 • up to 2 years from the start of treatment
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
8.1%
3/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Skin and subcutaneous tissue disorders
Vitiligo
|
8.1%
3/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Gastrointestinal disorders
Diarrhea
|
5.4%
2/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Gastrointestinal disorders
Mucositis
|
5.4%
2/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Endocrine disorders
Adrenal insufficiency
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Gastrointestinal disorders
Nausea
|
2.7%
1/37 • up to 2 years from the start of treatment
|
20.0%
1/5 • up to 2 years from the start of treatment
|
|
Metabolism and nutrition disorders
Anorexia
|
2.7%
1/37 • up to 2 years from the start of treatment
|
40.0%
2/5 • up to 2 years from the start of treatment
|
|
Eye disorders
Dry eyes
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
5.4%
2/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Metabolism and nutrition disorders
Failure to thrive
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Renal and urinary disorders
Hematuria
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Renal and urinary disorders
Proteinuria
|
5.4%
2/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Injury, poisoning and procedural complications
Bruising
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
General disorders
Gingival bleed
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Gastrointestinal disorders
Microscopic diverticular perforation
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Vascular disorders
Hypertension
|
5.4%
2/37 • up to 2 years from the start of treatment
|
40.0%
2/5 • up to 2 years from the start of treatment
|
|
Nervous system disorders
Headache
|
40.5%
15/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Nervous system disorders
Motor neuropathy
|
8.1%
3/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Nervous system disorders
Sensory neuropathy
|
8.1%
3/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Nervous system disorders
Stroke
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Nervous system disorders
Dysarthria
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Nervous system disorders
Tremor
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Nervous system disorders
Ataxia
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Nervous system disorders
Encephalitis
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
General disorders
General disorders and administration site conditions - Other, specify
|
0.00%
0/37 • up to 2 years from the start of treatment
|
20.0%
1/5 • up to 2 years from the start of treatment
|
|
Infections and infestations
Infections and infestations - Other, specify
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Injury, poisoning and procedural complications
Fall
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Metabolism and nutrition disorders
Hyponatremia
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Gastrointestinal disorders
Pain- Abdominal
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
General disorders
Pain
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Renal and urinary disorders
Urinary Tract Obstruction
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Infections and infestations
Parainfluenza
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Renal and urinary disorders
Urinary Incontinence
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Nervous system disorders
Intracranial Hemorrage
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Renal and urinary disorders
Acute Kidney Injury
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Vascular disorders
Thromboembolic Event
|
5.4%
2/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Cardiac disorders
Ventriculitis
|
2.7%
1/37 • up to 2 years from the start of treatment
|
0.00%
0/5 • up to 2 years from the start of treatment
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, specify
|
0.00%
0/37 • up to 2 years from the start of treatment
|
40.0%
2/5 • up to 2 years from the start of treatment
|
|
Eye disorders
Floaters
|
0.00%
0/37 • up to 2 years from the start of treatment
|
20.0%
1/5 • up to 2 years from the start of treatment
|
|
Vascular disorders
Vascular disorders - Other, specify
|
0.00%
0/37 • up to 2 years from the start of treatment
|
20.0%
1/5 • up to 2 years from the start of treatment
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/37 • up to 2 years from the start of treatment
|
20.0%
1/5 • up to 2 years from the start of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, specify
|
0.00%
0/37 • up to 2 years from the start of treatment
|
20.0%
1/5 • up to 2 years from the start of treatment
|
Additional Information
Harriet Kluger, MD
Harvey and Kate Cushing Professor of Medicine (Oncology) and of Dermatology; Director, Yale SPORE in Skin Cancer, Yale Cancer Center
Phone: (203) 200-6622
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place