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MEDI4736 and Tremelimumab in Treating Patients With Metastatic HER2 Negative Breast Cancer

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: NCT02536794
Recruitment Status : Completed
First Posted : September 1, 2015
Results First Posted : April 23, 2021
Last Update Posted : April 23, 2021
Sponsor:
Collaborators:
MedImmune LLC
Avon Breast Cancer Foundation
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Northwestern University

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Estrogen Receptor Negative
Estrogen Receptor Positive
HER2/Neu Negative
Recurrent Breast Carcinoma
Stage IV Breast Cancer
Interventions Biological: Anti-B7H1 Monoclonal Antibody MEDI4736
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Biological: Tremelimumab
Enrollment 30
Recruitment Details The study was opened to accrual on December 18 2015, with the first patient starting treatment on January 14, 2016 and a total accrual goal of 50 patients. The study closed to further accrual July 20, 2020 with 30 patients treated on study.
Pre-assignment Details  
Arm/Group Title Treatment (MEDI4736, Tremelimumab)
Hide Arm/Group Description

Patients receive anti-B7H1 monoclonal antibody MEDI4736 IV over 1 hour and tremelimumab IV over 1 hour on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Four weeks after the last combination dose, patients continue to receive anti-B7H1 monoclonal antibody MEDI4736 every 2 weeks for up to 18 additional doses in the absence of disease progression or unacceptable toxicity. Patients achieving PD or clinical benefit (CR, PR, or SD) may be retreated with anti-B7H1 monoclonal antibody MEDI4736 for an additional 52 weeks.

Anti-B7H1 Monoclonal Antibody MEDI4736: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Tremelimumab: Given IV

Period Title: Reached 1st Response Assessment
Started 30
Started Treatment 30
Attempted First Cycle 30
Attempted Second Cycle 24
Reached First Response 24
Completed 24
Not Completed 6
Reason Not Completed
Adverse Event             2
Progressive Disease             2
Withdrawal by Subject             1
Protocol Violation             1
Period Title: Continued Treatment After 1st Response
Started 24
Went on to Start Cycle 3 16
Completed 16
Not Completed 8
Reason Not Completed
Progressive disease             7
Adverse Event             1
Period Title: Follow up for 3 Years or Death
Started [1] 29 [2]
Completed 29
Not Completed 0
[1]
All patients who are treated on study go into the follow up phase
[2]
one patient did not go into follow up as treatment was discontinued due to a protocol violation
Arm/Group Title Treatment (MEDI4736, Tremelimumab)
Hide Arm/Group Description

Patients receive anti-B7H1 monoclonal antibody MEDI4736 IV over 1 hour and tremelimumab IV over 1 hour on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Four weeks after the last combination dose, patients continue to receive anti-B7H1 monoclonal antibody MEDI4736 every 2 weeks for up to 18 additional doses in the absence of disease progression or unacceptable toxicity. Patients achieving PD or clinical benefit (CR, PR, or SD) may be retreated with anti-B7H1 monoclonal antibody MEDI4736 for an additional 52 weeks.

Anti-B7H1 Monoclonal Antibody MEDI4736: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Tremelimumab: Given IV

Overall Number of Baseline Participants 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 30 participants
53.0
(35 to 83)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Female
30
 100.0%
Male
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Hispanic or Latino
4
  13.3%
Not Hispanic or Latino
25
  83.3%
Unknown or Not Reported
1
   3.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
   3.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
4
  13.3%
White
24
  80.0%
More than one race
0
   0.0%
Unknown or Not Reported
1
   3.3%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 30 participants
30
 100.0%
Received prior systemic therapies for breast cancer  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
30
 100.0%
Received prior chemotherapy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
No
1
   3.3%
yes
29
  96.7%
ER Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Negative
15
  50.0%
Positive
15
  50.0%
[1]
Measure Description: Estrogen Receptors (ER) status is determined the presence or absence of estrogen receptors in the breast cancer cells. ER positive is defined as 1% or greater.
PR Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Negative
22
  73.3%
Positive
8
  26.7%
[1]
Measure Description: progesterone receptor (PR) status is determined by the presence or absence of progresterone receptors in the breast cancer cells. PR positive will be defined as a result of greater than 10%.
Triple Negative Breast Cancer (TNBC)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
No
15
  50.0%
Yes
15
  50.0%
[1]
Measure Description: TBNC is breast cancer which is ER negative, PR negative and HER2 negative
HER 2 Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Positive
0
   0.0%
Negative
30
 100.0%
[1]
Measure Description: Human epidermal growth factor receptor 2 (HER2) status is determined to be positive (if the protein HER2 is present) or negative (protein HER2 is not present/present in very low levels).
1.Primary Outcome
Title Overall Response Rate (ORR) in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab
Hide Description

Overall response rate is defined as the number of patients with partial response (PR), plus those with complete response (CR) using the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 with the following definitions:

Complete Response - Disappearance of all lesions Partial Response - At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Time Frame Up to a maximum of 49 cycles where 1 cycle = 4 weeks for the first 4 cycles and than 1 cycle =2 weeks for 45 cycles
Hide Outcome Measure Data
Hide Analysis Population Description
Patients were required to complete 2 months of treatment to be evaluable for this endpoint
Arm/Group Title Treatment (MEDI4736, Tremelimumab)
Hide Arm/Group Description:

Patients receive anti-B7H1 monoclonal antibody MEDI4736 IV over 1 hour and tremelimumab IV over 1 hour on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Four weeks after the last combination dose, patients continue to receive anti-B7H1 monoclonal antibody MEDI4736 every 2 weeks for up to 18 additional doses in the absence of disease progression or unacceptable toxicity. Patients achieving PD or clinical benefit (CR, PR, or SD) may be retreated with anti-B7H1 monoclonal antibody MEDI4736 for an additional 52 weeks.

Anti-B7H1 Monoclonal Antibody MEDI4736: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Tremelimumab: Given IV

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: participants
4
2.Primary Outcome
Title Overall Response Rate (ORR) in Patients With Triple Negative Breast Cancer (TNBC) Treated With Durvalumab in Combination With Tremelimumab
Hide Description

Overall response rate is defined as the number of patients with partial response (PR), plus those with complete response (CR) using the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 with the following definitions:

Complete Response - Disappearance of all lesions Partial Response - At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

TNBC = patients whose status for ER, PR and HER2 is negative

Time Frame Up to a maximum of 49 cycles where 1 cycle = 4 weeks for the first 4 cycles and then 1 cycle = 2 weeks for up to 45 cycles
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol patients were required to complete 2 months of study treatment to be evaluable for this endpoint, however, the study was closed before this cohort of patients reached its planned sample size and so all TNBC patients with a response are reported here.
Arm/Group Title Treatment (MEDI4736, Tremelimumab)
Hide Arm/Group Description:

Patients receive anti-B7H1 monoclonal antibody MEDI4736 IV over 1 hour and tremelimumab IV over 1 hour on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Four weeks after the last combination dose, patients continue to receive anti-B7H1 monoclonal antibody MEDI4736 every 2 weeks for up to 18 additional doses in the absence of disease progression or unacceptable toxicity. Patients achieving PD or clinical benefit (CR, PR, or SD) may be retreated with anti-B7H1 monoclonal antibody MEDI4736 for an additional 52 weeks.

Anti-B7H1 Monoclonal Antibody MEDI4736: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Tremelimumab: Given IV

Overall Number of Participants Analyzed 15
Measure Type: Number
Unit of Measure: participants
4
3.Secondary Outcome
Title Toxicity in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab
Hide Description

Toxicity will be evaluated by the number, frequency, and severity of adverse events as defined by the NCI Common Terminology Criteria for Adverse Events or CTCAE version 4.03

Events that were considered to at least be possibly related to either study drugs are reported here and in general grading is as follows:

Mild (grade 1): the event causes discomfort without disruption of normal daily activities Moderate (grade 2): the event causes discomfort that affects normal daily activities Severe (grade 3): the event makes the patient unable to perform normal daily activities or significantly affects his/her clinical status Life-threatening (grade 4): the patient was at risk of death at the time of the event Fatal (grade 5): the event caused death

Time Frame Up to a maximum of 49 cycles where 1 cycle = 4 weeks for the first 4 cycles and than 1 cycle =2 weeks for 45 cycles
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (MEDI4736, Tremelimumab)
Hide Arm/Group Description:

Patients receive anti-B7H1 monoclonal antibody MEDI4736 IV over 1 hour and tremelimumab IV over 1 hour on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Four weeks after the last combination dose, patients continue to receive anti-B7H1 monoclonal antibody MEDI4736 every 2 weeks for up to 18 additional doses in the absence of disease progression or unacceptable toxicity. Patients achieving PD or clinical benefit (CR, PR, or SD) may be retreated with anti-B7H1 monoclonal antibody MEDI4736 for an additional 52 weeks.

Anti-B7H1 Monoclonal Antibody MEDI4736: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Tremelimumab: Given IV

Overall Number of Participants Analyzed 30
Measure Type: Number
Unit of Measure: participants
Grade 1 or 2 Adverse Event 27
Grade 3 or 4 Adverse Event 12
Grade 1 or 2 Serious Adverse Event 6
Grade 3 or 4 Serious Adverse Event 7
4.Secondary Outcome
Title Overall Survival (OS) in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab
Hide Description OS is defined as the time from treatment initiation until death due to any cause
Time Frame Time from treatment initiation until 3 years post treatment continuation where patients were treated up to a maximum of 49 cycles where 1 cycle = 4 weeks for the first 4 cycles and than 1 cycle =2 weeks for 45 cycles
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Progression Free Survival (PFS) in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab
Hide Description PFS is defined as the time from treatment initiation to documented disease progression. Progressive Disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression.)
Time Frame Time from treatment initiation until 3 years post treatment continuation where patients were treated up to a maximum of 49 cycles where 1 cycle = 4 weeks,for the first 4 cycles and than 1 cycle =2 weeks for 45 cycles
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Clinical Benefit Rate (CBR) in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab
Hide Description

CBR is defined as the number of patients with complete response (CR) plus those with partial response (PR) plus those with stable disease (SD) for ≥ 12 weeks using Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 with the following definitions:

Complete Response - Disappearance of all lesions Partial Response - At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters Stable Disease - Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of diameters while on study

Time Frame Up to a maximum of 49 cycles where 1 cycle = 4 weeks for the first 4 cycles and than 1 cycle =2 weeks for 45 cycles
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol patients were required to complete 2 months of study treatment to be evaluable for this endpoint, however all patients who had a response are reported here as the study did not meet its total sample size
Arm/Group Title Treatment (MEDI4736, Tremelimumab)
Hide Arm/Group Description:

Patients receive anti-B7H1 monoclonal antibody MEDI4736 IV over 1 hour and tremelimumab IV over 1 hour on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Four weeks after the last combination dose, patients continue to receive anti-B7H1 monoclonal antibody MEDI4736 every 2 weeks for up to 18 additional doses in the absence of disease progression or unacceptable toxicity. Patients achieving PD or clinical benefit (CR, PR, or SD) may be retreated with anti-B7H1 monoclonal antibody MEDI4736 for an additional 52 weeks.

Anti-B7H1 Monoclonal Antibody MEDI4736: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Tremelimumab: Given IV

Overall Number of Participants Analyzed 27
Measure Type: Number
Unit of Measure: participants
5
7.Other Pre-specified Outcome
Title Tumor Infiltrating Lymphocytes (TILs) Expression
Hide Description To evaluate if tissue-based immunohistochemical expression of TILs predicts response to MEDI4736 in combination with tremelimumab. Changes will also be analyzed to assess for pharmacodynamic effects of treatment
Time Frame Baseline and at 2 months of treatment
Outcome Measure Data Not Reported
8.Other Pre-specified Outcome
Title Programmed Death-ligand 1 (PD-L1) Expression
Hide Description To evaluate if tissue-based immunohistochemical expression of PD-L1 predicts response to MEDI4736 in combination with tremelimumab. Changes will also be analyzed to assess for pharmacodynamic effects of treatment
Time Frame Baseline and at 2 months of treatment
Outcome Measure Data Not Reported
9.Other Pre-specified Outcome
Title Change in T Cell Receptor Genotype
Hide Description To evaluate if tissue-based immunohistochemical expression of T cell receptor genotype predicts response to MEDI4736 in combination with tremelimumab. Changes will also be analyzed to assess for pharmacodynamic effects of treatment
Time Frame Baseline and at 2 months of treatment
Outcome Measure Data Not Reported
10.Other Pre-specified Outcome
Title Changes in Peripheral T Cell Subpopulations
Hide Description To evaluate if tissue-based immunohistochemical expression of peripheral T cell subpopulations predicts response to MEDI4736 in combination with tremelimumab. Changes will also be analyzed to assess for pharmacodynamic effects of treatment
Time Frame Baseline and at 2 months of treatment
Outcome Measure Data Not Reported
11.Other Pre-specified Outcome
Title Human Leukocyte Antigen (HLA)
Hide Description To evaluate if tissue-based immunohistochemical expression of HLA predicts response to MEDI4736 in combination with tremelimumab
Time Frame Baseline and at 2 months of treatment
Outcome Measure Data Not Reported
12.Other Pre-specified Outcome
Title Immune-related Candidate Gene Signatures
Hide Description To evaluate if tissue-based immunohistochemical expression of Immune-related candidate gene signatures predicts response to MEDI4736 in combination with tremelimumab
Time Frame Baseline and at 2 months of treatment
Outcome Measure Data Not Reported
13.Post-Hoc Outcome
Title Response in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab
Hide Description

Patients response is defined as the best response to treatment whilst on study using Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 with the following definitions:

Complete Response - Disappearance of all lesions Partial Response - At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters Stable Disease - Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of diameters while on study Progressive Disease - At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression.)

Time Frame Up to a maximum of 49 cycles where 1 cycle = 4 weeks for the first 4 cycles and than 1 cycle =2 weeks for 45 cycles
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (MEDI4736, Tremelimumab)
Hide Arm/Group Description:

Patients receive anti-B7H1 monoclonal antibody MEDI4736 IV over 1 hour and tremelimumab IV over 1 hour on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Four weeks after the last combination dose, patients continue to receive anti-B7H1 monoclonal antibody MEDI4736 every 2 weeks for up to 18 additional doses in the absence of disease progression or unacceptable toxicity. Patients achieving PD or clinical benefit (CR, PR, or SD) may be retreated with anti-B7H1 monoclonal antibody MEDI4736 for an additional 52 weeks.

Anti-B7H1 Monoclonal Antibody MEDI4736: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Tremelimumab: Given IV

Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response
1
   3.3%
Partial Response
3
  10.0%
Stable Disease
4
  13.3%
Progressive Disease
19
  63.3%
Not evaluable
3
  10.0%
14.Post-Hoc Outcome
Title Overall Response Rate (ORR) in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab (All Included)
Hide Description

Overall response rate is defined as the number of patients with partial response (PR), plus those with complete response (CR) using the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 with the following definitions:

Complete Response - Disappearance of all lesions Partial Response - At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Time Frame Up to a maximum of 49 cycles where 1 cycle = 4 weeks for the first 4 cycles and than 1 cycle =2 weeks for 45 cycles
Hide Outcome Measure Data
Hide Analysis Population Description
This includes patients who did not complete 2 months of treatment but would otherwise be evaluable for the endpoint
Arm/Group Title Treatment (MEDI4736, Tremelimumab)
Hide Arm/Group Description:

Patients receive anti-B7H1 monoclonal antibody MEDI4736 IV over 1 hour and tremelimumab IV over 1 hour on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Four weeks after the last combination dose, patients continue to receive anti-B7H1 monoclonal antibody MEDI4736 every 2 weeks for up to 18 additional doses in the absence of disease progression or unacceptable toxicity. Patients achieving PD or clinical benefit (CR, PR, or SD) may be retreated with anti-B7H1 monoclonal antibody MEDI4736 for an additional 52 weeks.

Anti-B7H1 Monoclonal Antibody MEDI4736: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Tremelimumab: Given IV

Overall Number of Participants Analyzed 27
Measure Type: Number
Unit of Measure: participants
4
Time Frame Adverse events are collected from the time of treatment initiation until 30 days post last treatment. Adverse events were collected up to a maximum of 49 cycles where 1 cycle = 4 weeks for the first 4 cycles and than 1 cycle =2 weeks for 45 cycles.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment (MEDI4736, Tremelimumab)
Hide Arm/Group Description

Patients receive anti-B7H1 monoclonal antibody MEDI4736 IV over 1 hour and tremelimumab IV over 1 hour on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Four weeks after the last combination dose, patients continue to receive anti-B7H1 monoclonal antibody MEDI4736 every 2 weeks for up to 18 additional doses in the absence of disease progression or unacceptable toxicity. Patients achieving PD or clinical benefit (CR, PR, or SD) may be retreated with anti-B7H1 monoclonal antibody MEDI4736 for an additional 52 weeks.

Anti-B7H1 Monoclonal Antibody MEDI4736: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Tremelimumab: Given IV

All-Cause Mortality
Treatment (MEDI4736, Tremelimumab)
Affected / at Risk (%)
Total   22/30 (73.33%)    
Hide Serious Adverse Events
Treatment (MEDI4736, Tremelimumab)
Affected / at Risk (%) # Events
Total   18/30 (60.00%)    
Cardiac disorders   
Myocarditis and Ventricular Tachycardia  1  1/30 (3.33%)  1
Gastrointestinal disorders   
Vomiting  1  1/30 (3.33%)  1
Vomiting  1 [1]  1/30 (3.33%)  1
Enteritis  1 [2]  1/30 (3.33%)  1
General disorders   
Fever and chills  1 [3]  2/30 (6.67%)  2
Fever  1 [4]  1/30 (3.33%)  1
Hepatobiliary disorders   
Hepatitis  1  2/30 (6.67%)  2
Hepatitis  1 [5]  1/30 (3.33%)  1
Infections and infestations   
Spontaneous bacterial peritonitis  1  1/30 (3.33%)  1
Urosepsis  1 [6]  1/30 (3.33%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Disease progression  1  2/30 (6.67%)  2
Disease progression  1 [7]  1/30 (3.33%)  1
Disease progression  1 [8]  1/30 (3.33%)  1
Pseudoprogression  1 [9]  1/30 (3.33%)  1
Nervous system disorders   
Confusion  1  2/30 (6.67%)  2
Dizziness  1 [10]  1/30 (3.33%)  1
Renal and urinary disorders   
Nephritis  1  1/30 (3.33%)  1
Respiratory, thoracic and mediastinal disorders   
Pleural effusion  1  1/30 (3.33%)  1
Shortness of breath  1  1/30 (3.33%)  1
Respiratory failure  1 [11]  1/30 (3.33%)  2
1
Term from vocabulary, CTCAE (4.03)
Indicates events were collected by systematic assessment
[1]
Patient also experienced diarrhea during this event
[2]
Patient also experienced increased INR at the time of the event
[3]
one patient also experienced elevated AST and hepatic hemorrhage at the time of the event
[4]
Patient also experienced weakness at the time of the event
[5]
Patient also experienced pain during this event
[6]
Patient also experienced pain and delirium during this event
[7]
Patient also experienced hypersomnia during this event
[8]
Patient also experience anorexia and edema in limbs at the time of this event
[9]
Patient also experienced fever, left arm weakness and gait disturbance during this event
[10]
Patient also experienced headaches and vomiting at the time of this event
[11]
patient experienced pleural effusion and pneumonitis during this event
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment (MEDI4736, Tremelimumab)
Affected / at Risk (%) # Events
Total   30/30 (100.00%)    
Blood and lymphatic system disorders   
Anemia  1  15/30 (50.00%) 
Cardiac disorders   
Palpitations  1  1/30 (3.33%) 
Sinus tachycardia  1  3/30 (10.00%) 
Ear and labyrinth disorders   
Ear pain  1  1/30 (3.33%) 
Endocrine disorders   
Hyperthyroidism  1  2/30 (6.67%) 
Hypothyroidism  1  4/30 (13.33%) 
Eye disorders   
Blurred vision  1  1/30 (3.33%) 
Floaters  1  1/30 (3.33%) 
Gastrointestinal disorders   
Abdominal pain  1  8/30 (26.67%) 
Bloating  1  1/30 (3.33%) 
Constipation  1  5/30 (16.67%) 
Colitis  1  1/30 (3.33%) 
Dental caries  1  1/30 (3.33%) 
Diarrhea  1  6/30 (20.00%) 
Dry mouth  1  1/30 (3.33%) 
Dehydration  1  1/30 (3.33%) 
Fecal incontinence  1  1/30 (3.33%) 
Flatulence  1  1/30 (3.33%) 
Gastroesophageal reflux disease  1  1/30 (3.33%) 
Mucositis oral  1  1/30 (3.33%) 
Nausea  1  6/30 (20.00%) 
Oral pain  1  1/30 (3.33%) 
Vomiting  1  4/30 (13.33%) 
General disorders   
Chills  1  1/30 (3.33%) 
Edema limbs  1  1/30 (3.33%) 
Fatigue  1  11/30 (36.67%) 
Fever  1  2/30 (6.67%) 
Flu like symptoms  1  1/30 (3.33%) 
Night sweats  1  1/30 (3.33%) 
Breast leison discomfort  1  1/30 (3.33%) 
Discomfort  1  1/30 (3.33%) 
Non-cardiac chest pain  1  2/30 (6.67%) 
Pain  1  4/30 (13.33%) 
Infections and infestations   
Pharyngitis  1  1/30 (3.33%) 
Rash pustular  1  1/30 (3.33%) 
Sinusitis  1  1/30 (3.33%) 
Skin infection  1  1/30 (3.33%) 
Upper respiratory infection  1  2/30 (6.67%) 
Vaginal infection  1  1/30 (3.33%) 
Injury, poisoning and procedural complications   
Fall  1  1/30 (3.33%) 
Investigations   
Activated partial thromboplastin time prolonged  1  9/30 (30.00%) 
Alanine aminotransferase increased  1  9/30 (30.00%) 
Alkaline phosphatase increased  1  11/30 (36.67%) 
Aspartate aminotransferase increased  1  9/30 (30.00%) 
Blood bilirubin increased  1  7/30 (23.33%) 
Cardiac troponin I increased  1  1/30 (3.33%) 
Creatinine increased  1  3/30 (10.00%) 
Electrocardiogram QT corrected interval prolonged  1  1/30 (3.33%) 
GGT increased  1  8/30 (26.67%) 
Hemoglobin increased  1  1/30 (3.33%) 
INR increased  1  4/30 (13.33%) 
low GFR (clinically significant)  1  1/30 (3.33%) 
LV diastolic dysfunction  1  1/30 (3.33%) 
Lipase increased  1  6/30 (20.00%) 
Lymphocyte count decreased  1  13/30 (43.33%) 
Neutrophil count decreased  1  1/30 (3.33%) 
Platelet count decreased  1  7/30 (23.33%) 
Serum amylase increased  1  3/30 (10.00%) 
Weight gain  1  1/30 (3.33%) 
Weight loss  1  1/30 (3.33%) 
White blood cell decreased  1  4/30 (13.33%) 
Metabolism and nutrition disorders   
Anorexia  1  2/30 (6.67%) 
Alkalosis  1  1/30 (3.33%) 
Hypercalcemia  1  2/30 (6.67%) 
Hyperglycemia  1  18/30 (60.00%) 
Hyperkalemia  1  1/30 (3.33%) 
Hypermagnesemia  1  4/30 (13.33%) 
Hypernatremia  1  2/30 (6.67%) 
Hypoalbuminemia  1  16/30 (53.33%) 
Hypocalcemia  1  5/30 (16.67%) 
Hypoglycemia  1  2/30 (6.67%) 
Hypokalemia  1  4/30 (13.33%) 
Hypomagnesemia  1  10/30 (33.33%) 
Hyponatremia  1  6/30 (20.00%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  1/30 (3.33%) 
Back pain  1  3/30 (10.00%) 
Bone pain  1  1/30 (3.33%) 
joint stiffness (feet)  1  1/30 (3.33%) 
generalized aches and pains  1  1/30 (3.33%) 
cancer related pain  1  1/30 (3.33%) 
bilateral hand stiffness  1  1/30 (3.33%) 
Neck pain  1  1/30 (3.33%) 
Pain in extremity  1  4/30 (13.33%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
disease progression  1  1/30 (3.33%) 
Nervous system disorders   
Dizziness  1  1/30 (3.33%) 
Headache  1  3/30 (10.00%) 
Nervous system disorder NOS  1  1/30 (3.33%) 
Ptosis  1  1/30 (3.33%) 
Peripheral sensory neuropathy  1  2/30 (6.67%) 
Psychiatric disorders   
Anxiety  1  1/30 (3.33%) 
Confusion  1  1/30 (3.33%) 
Insomnia  1  3/30 (10.00%) 
Renal and urinary disorders   
Proteinuria  1  1/30 (3.33%) 
Urinary incontinence  1  1/30 (3.33%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  1/30 (3.33%) 
Dyspnea  1  2/30 (6.67%) 
Hypoxia  1  1/30 (3.33%) 
Nasal congestion  1  1/30 (3.33%) 
Pleural effusion  1  2/30 (6.67%) 
Postnasal drip  1  1/30 (3.33%) 
Pulmonary edema  1  1/30 (3.33%) 
Sore throat  1  1/30 (3.33%) 
Pleuritic pain  1  1/30 (3.33%) 
Skin and subcutaneous tissue disorders   
Dry skin  1  1/30 (3.33%) 
Pruritus  1  6/30 (20.00%) 
Rash maculo-papular  1  5/30 (16.67%) 
Skin ulceration  1  1/30 (3.33%) 
Vascular disorders   
Lymphedema  1  1/30 (3.33%) 
Thromboembolic event  1  2/30 (6.67%) 
1
Term from vocabulary, CTCAE (4.03)
Indicates events were collected by systematic assessment
The study was closed before reaching the planned total sample size of 50 patients due to slow accrual.
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: Massimo Cristofanilli
Organization: Northwestern University
Phone: 312 503 5488
EMail: Massimo.cristofanilli@nm.org
Layout table for additonal information
Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT02536794    
Other Study ID Numbers: NU 15B01
NCI-2015-01445 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ESR-14-10694
D4190C00030
STU00200984
NU 15B01 ( Other Identifier: Northwestern University )
P30CA060553 ( U.S. NIH Grant/Contract )
First Submitted: August 28, 2015
First Posted: September 1, 2015
Results First Submitted: March 26, 2021
Results First Posted: April 23, 2021
Last Update Posted: April 23, 2021