Trial Outcomes & Findings for MK-3475 in Melanoma and NSCLC Patients With Brain Metastases (NCT NCT02085070)
NCT ID: NCT02085070
Last Updated: 2021-03-24
Results Overview
RECIST criteria v1.1 was modified to account for differences in measuring the response of clinically evaluable brain lesions as opposed to systemic lesions (modified RECIST, or mRECIST). Size was considered the tumor's largest diameter. Measurements from multiple lesions were summed to calculate the sum of the diameters (SD). The SD calculated on a baseline scan performed within 28 days of study drug initiation was used as a reference to determine the objective response of the clinically evaluable lesions. mRECIST differ from RECIST v1.0 in allowing lesions measuring 5mm or less for response evaluation, provided that the MRI slice thickness was no more than 2.5mm. Seeing that the primary trial endpoint was brain metastasis response, up to 5 lesions were used for evaluation. Complete response (CR) constitutes complete disappearance of all target lesions, partial response (PR) constitutes \>= 30% decrease in the sum of the sum of the largest diameter of target
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
65 participants
Primary outcome timeframe
8 weeks
Results posted on
2021-03-24
Participant Flow
29 NSCLC patients were ineligible based on PD-L1.
Patients were assigned to a cohort based on tumor type.
Participant milestones
| Measure |
Melanoma Patients
After establishing eligibility criteria, for patients with melanoma the investigator will determine at least one lesion that requires local therapy (surgical resection or LITT) based on size, location, and/or risk of hemorrhage; this will be considered the "surgical lesion". All other eligible brain lesions will be considered "clinically evaluable lesions" and will be followed by modified RECIST (mRECIST) criteria to determine best response.
MK-3475: IV MK-3475
|
Non-small Cell Lung Cancer Patients
NSCLC patients are not required to have a "surgical lesion" but must have at least one "clinically evaluable lesion" in the central nervous system. Patients on NSCLC are required to have formalin-fixed, paraffin-embedded tumor tissue available for biomarker analysis.
MK-3475: IV MK-3475
|
|---|---|---|
|
Overall Study
STARTED
|
23
|
42
|
|
Overall Study
COMPLETED
|
23
|
42
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
MK-3475 in Melanoma and NSCLC Patients With Brain Metastases
Baseline characteristics by cohort
| Measure |
Melanoma Patients
n=23 Participants
After establishing eligibility criteria, for patients with melanoma the investigator will determine at least one lesion that requires local therapy (surgical resection or LITT) based on size, location, and/or risk of hemorrhage; this will be considered the "surgical lesion". All other eligible brain lesions will be considered "clinically evaluable lesions" and will be followed by modified RECIST (mRECIST) criteria to determine best response.
MK-3475: IV MK-3475
|
Non-small Cell Lung Cancer Patients
n=42 Participants
NSCLC patients are not required to have a "surgical lesion" but must have at least one "clinically evaluable lesion" in the central nervous system. Patients on NSCLC are required to have formalin-fixed, paraffin-embedded tumor tissue available for biomarker analysis.
MK-3475: IV MK-3475
|
Total
n=65 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
10 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
13 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
23 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
59 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
23 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
58 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
23 participants
n=5 Participants
|
42 participants
n=7 Participants
|
65 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: modified RECIST 1.1 was used to determine response
RECIST criteria v1.1 was modified to account for differences in measuring the response of clinically evaluable brain lesions as opposed to systemic lesions (modified RECIST, or mRECIST). Size was considered the tumor's largest diameter. Measurements from multiple lesions were summed to calculate the sum of the diameters (SD). The SD calculated on a baseline scan performed within 28 days of study drug initiation was used as a reference to determine the objective response of the clinically evaluable lesions. mRECIST differ from RECIST v1.0 in allowing lesions measuring 5mm or less for response evaluation, provided that the MRI slice thickness was no more than 2.5mm. Seeing that the primary trial endpoint was brain metastasis response, up to 5 lesions were used for evaluation. Complete response (CR) constitutes complete disappearance of all target lesions, partial response (PR) constitutes \>= 30% decrease in the sum of the sum of the largest diameter of target
Outcome measures
| Measure |
Melanoma Patients
n=23 Participants
After establishing eligibility criteria, for patients with melanoma the investigator will determine at least one lesion that requires local therapy (surgical resection or LITT) based on size, location, and/or risk of hemorrhage; this will be considered the "surgical lesion". All other eligible brain lesions will be considered "clinically evaluable lesions" and will be followed by modified RECIST (mRECIST) criteria to determine best response.
MK-3475: IV MK-3475
|
Non-small Cell Lung Cancer Patients
n=42 Participants
NSCLC patients are not required to have a "surgical lesion" but must have at least one "clinically evaluable lesion" in the central nervous system. Patients on NSCLC are required to have formalin-fixed, paraffin-embedded tumor tissue available for biomarker analysis.
MK-3475: IV MK-3475
|
|---|---|---|
|
Overall Response in the Brain by mRECIST
progression/stable
|
17 participants
|
31 participants
|
|
Overall Response in the Brain by mRECIST
better response
|
6 participants
|
11 participants
|
Adverse Events
Melanoma Patients
Serious events: 5 serious events
Other events: 13 other events
Deaths: 16 deaths
Non-small Cell Lung Cancer Patients
Serious events: 5 serious events
Other events: 35 other events
Deaths: 35 deaths
Serious adverse events
| Measure |
Melanoma Patients
n=23 participants at risk
After establishing eligibility criteria, for patients with melanoma the investigator will determine at least one lesion that requires local therapy (surgical resection or LITT) based on size, location, and/or risk of hemorrhage; this will be considered the "surgical lesion". All other eligible brain lesions will be considered "clinically evaluable lesions" and will be followed by modified RECIST (mRECIST) criteria to determine best response.
MK-3475: IV MK-3475
|
Non-small Cell Lung Cancer Patients
n=42 participants at risk
NSCLC patients are not required to have a "surgical lesion" but must have at least one "clinically evaluable lesion" in the central nervous system. Patients on NSCLC are required to have formalin-fixed, paraffin-embedded tumor tissue available for biomarker analysis.
MK-3475: IV MK-3475
|
|---|---|---|
|
Psychiatric disorders
Confusion
|
8.7%
2/23 • Number of events 2 • 2 Years
|
0.00%
0/42 • 2 Years
|
|
Skin and subcutaneous tissue disorders
Rash
|
4.3%
1/23 • Number of events 1 • 2 Years
|
0.00%
0/42 • 2 Years
|
|
General disorders
Fever
|
4.3%
1/23 • Number of events 1 • 2 Years
|
0.00%
0/42 • 2 Years
|
|
Nervous system disorders
Seizure
|
4.3%
1/23 • Number of events 1 • 2 Years
|
0.00%
0/42 • 2 Years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/23 • 2 Years
|
4.8%
2/42 • Number of events 2 • 2 Years
|
|
Renal and urinary disorders
Acute Kidney Injury
|
0.00%
0/23 • 2 Years
|
2.4%
1/42 • Number of events 1 • 2 Years
|
|
Endocrine disorders
Adrenal Insufficienvy
|
0.00%
0/23 • 2 Years
|
2.4%
1/42 • Number of events 1 • 2 Years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/23 • 2 Years
|
2.4%
1/42 • Number of events 1 • 2 Years
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/23 • 2 Years
|
2.4%
1/42 • Number of events 1 • 2 Years
|
Other adverse events
| Measure |
Melanoma Patients
n=23 participants at risk
After establishing eligibility criteria, for patients with melanoma the investigator will determine at least one lesion that requires local therapy (surgical resection or LITT) based on size, location, and/or risk of hemorrhage; this will be considered the "surgical lesion". All other eligible brain lesions will be considered "clinically evaluable lesions" and will be followed by modified RECIST (mRECIST) criteria to determine best response.
MK-3475: IV MK-3475
|
Non-small Cell Lung Cancer Patients
n=42 participants at risk
NSCLC patients are not required to have a "surgical lesion" but must have at least one "clinically evaluable lesion" in the central nervous system. Patients on NSCLC are required to have formalin-fixed, paraffin-embedded tumor tissue available for biomarker analysis.
MK-3475: IV MK-3475
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
8.7%
2/23 • Number of events 2 • 2 Years
|
14.3%
6/42 • Number of events 6 • 2 Years
|
|
Gastrointestinal disorders
Colitis
|
8.7%
2/23 • Number of events 2 • 2 Years
|
0.00%
0/42 • 2 Years
|
|
Gastrointestinal disorders
Constipation
|
8.7%
2/23 • Number of events 2 • 2 Years
|
50.0%
21/42 • Number of events 30 • 2 Years
|
|
Gastrointestinal disorders
Diarrhea
|
13.0%
3/23 • Number of events 3 • 2 Years
|
33.3%
14/42 • Number of events 26 • 2 Years
|
|
Gastrointestinal disorders
Nausea
|
30.4%
7/23 • Number of events 7 • 2 Years
|
28.6%
12/42 • Number of events 17 • 2 Years
|
|
Gastrointestinal disorders
Vomiting
|
8.7%
2/23 • Number of events 2 • 2 Years
|
9.5%
4/42 • Number of events 6 • 2 Years
|
|
General disorders
Chills
|
8.7%
2/23 • Number of events 2 • 2 Years
|
2.4%
1/42 • Number of events 1 • 2 Years
|
|
General disorders
Fatigue
|
56.5%
13/23 • Number of events 13 • 2 Years
|
83.3%
35/42 • Number of events 65 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.7%
2/23 • Number of events 2 • 2 Years
|
7.1%
3/42 • Number of events 3 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.7%
2/23 • Number of events 2 • 2 Years
|
42.9%
18/42 • Number of events 26 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Pain
|
13.0%
3/23 • Number of events 4 • 2 Years
|
9.5%
4/42 • Number of events 10 • 2 Years
|
|
Nervous system disorders
Ataxia
|
13.0%
3/23 • Number of events 3 • 2 Years
|
0.00%
0/42 • 2 Years
|
|
Nervous system disorders
Cognitive disturbance
|
8.7%
2/23 • Number of events 2 • 2 Years
|
4.8%
2/42 • Number of events 2 • 2 Years
|
|
Nervous system disorders
Confusion
|
8.7%
2/23 • Number of events 2 • 2 Years
|
0.00%
0/42 • 2 Years
|
|
Nervous system disorders
Dizziness
|
8.7%
2/23 • Number of events 2 • 2 Years
|
23.8%
10/42 • Number of events 13 • 2 Years
|
|
Nervous system disorders
Dysphasia
|
8.7%
2/23 • Number of events 2 • 2 Years
|
0.00%
0/42 • 2 Years
|
|
Nervous system disorders
Gait disturbance
|
8.7%
2/23 • Number of events 2 • 2 Years
|
0.00%
0/42 • 2 Years
|
|
Nervous system disorders
Headache
|
13.0%
3/23 • Number of events 3 • 2 Years
|
35.7%
15/42 • Number of events 30 • 2 Years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
13.0%
3/23 • Number of events 3 • 2 Years
|
61.9%
26/42 • Number of events 42 • 2 Years
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
8.7%
2/23 • Number of events 2 • 2 Years
|
4.8%
2/42 • Number of events 3 • 2 Years
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
17.4%
4/23 • Number of events 4 • 2 Years
|
11.9%
5/42 • Number of events 9 • 2 Years
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
13.0%
3/23 • Number of events 3 • 2 Years
|
23.8%
10/42 • Number of events 11 • 2 Years
|
|
Endocrine disorders
Hypothyroidism
|
4.3%
1/23 • Number of events 1 • 2 Years
|
14.3%
6/42 • Number of events 8 • 2 Years
|
|
Eye disorders
Floaters
|
0.00%
0/23 • 2 Years
|
9.5%
4/42 • Number of events 5 • 2 Years
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/23 • 2 Years
|
7.1%
3/42 • Number of events 3 • 2 Years
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
0.00%
0/23 • 2 Years
|
7.1%
3/42 • Number of events 4 • 2 Years
|
|
General disorders
Edema limbs
|
0.00%
0/23 • 2 Years
|
23.8%
10/42 • Number of events 14 • 2 Years
|
|
General disorders
Fever
|
4.3%
1/23 • Number of events 1 • 2 Years
|
7.1%
3/42 • Number of events 5 • 2 Years
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/23 • 2 Years
|
11.9%
5/42 • Number of events 5 • 2 Years
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/23 • 2 Years
|
7.1%
3/42 • Number of events 5 • 2 Years
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/23 • 2 Years
|
7.1%
3/42 • Number of events 4 • 2 Years
|
|
Investigations
Creatinine increased
|
0.00%
0/23 • 2 Years
|
7.1%
3/42 • Number of events 4 • 2 Years
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/23 • 2 Years
|
40.5%
17/42 • Number of events 25 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/23 • 2 Years
|
7.1%
3/42 • Number of events 5 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
0.00%
0/23 • 2 Years
|
7.1%
3/42 • Number of events 4 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
4.3%
1/23 • Number of events 1 • 2 Years
|
9.5%
4/42 • Number of events 6 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/23 • 2 Years
|
7.1%
3/42 • Number of events 3 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
4.3%
1/23 • Number of events 1 • 2 Years
|
31.0%
13/42 • Number of events 25 • 2 Years
|
|
Nervous system disorders
Seizure
|
4.3%
1/23 • Number of events 1 • 2 Years
|
7.1%
3/42 • Number of events 5 • 2 Years
|
|
Psychiatric disorders
Anxiety
|
4.3%
1/23 • Number of events 1 • 2 Years
|
21.4%
9/42 • Number of events 11 • 2 Years
|
|
Psychiatric disorders
Depression
|
0.00%
0/23 • 2 Years
|
7.1%
3/42 • Number of events 3 • 2 Years
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/23 • 2 Years
|
16.7%
7/42 • Number of events 8 • 2 Years
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
4.3%
1/23 • Number of events 1 • 2 Years
|
11.9%
5/42 • Number of events 7 • 2 Years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/23 • 2 Years
|
50.0%
21/42 • Number of events 28 • 2 Years
|
|
Vascular disorders
Hypertension
|
0.00%
0/23 • 2 Years
|
16.7%
7/42 • Number of events 8 • 2 Years
|
|
Vascular disorders
Thromboembolic event
|
0.00%
0/23 • 2 Years
|
14.3%
6/42 • Number of events 7 • 2 Years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place