Trial Outcomes & Findings for MEDI4736 and Tremelimumab in Treating Patients With Metastatic HER2 Negative Breast Cancer (NCT NCT02536794)

NCT ID: NCT02536794

Last Updated: 2022-05-17

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 30 participants
• Primary outcome timeframe: 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
• Results posted on: 2022-05-17

Participant Flow

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.

Participant milestones

Measure	Treatment (MEDI4736, Tremelimumab) 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
Reached 1st Response Assessment STARTED	30
Reached 1st Response Assessment Started Treatment	30
Reached 1st Response Assessment Attempted First Cycle	30
Reached 1st Response Assessment Attempted Second Cycle	24
Reached 1st Response Assessment Reached First Response	24
Reached 1st Response Assessment COMPLETED	24
Reached 1st Response Assessment NOT COMPLETED	6
Continued Treatment After 1st Response STARTED	24
Continued Treatment After 1st Response Went on to Start Cycle 3	16
Continued Treatment After 1st Response COMPLETED	16
Continued Treatment After 1st Response NOT COMPLETED	8
Follow up for 3 Years or Death STARTED	29
Follow up for 3 Years or Death COMPLETED	29
Follow up for 3 Years or Death NOT COMPLETED	0

Reasons for withdrawal

Measure	Treatment (MEDI4736, Tremelimumab) 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
Reached 1st Response Assessment Adverse Event	2
Reached 1st Response Assessment Progressive Disease	2
Reached 1st Response Assessment Withdrawal by Subject	1
Reached 1st Response Assessment Protocol Violation	1
Continued Treatment After 1st Response Progressive disease	7
Continued Treatment After 1st Response Adverse Event	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Treatment (MEDI4736, Tremelimumab) n=30 Participants 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
Age, Continuous	53.0 years n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants
Race (NIH/OMB) White	24 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	30 Participants n=5 Participants
Received prior systemic therapies for breast cancer	30 Participants n=5 Participants
Received prior chemotherapy No	1 Participants n=5 Participants
Received prior chemotherapy yes	29 Participants n=5 Participants
ER Status Negative	15 Participants n=5 Participants
ER Status Positive	15 Participants n=5 Participants
PR Status Negative	22 Participants n=5 Participants
PR Status Positive	8 Participants n=5 Participants
Triple Negative Breast Cancer (TNBC) No	15 Participants n=5 Participants
Triple Negative Breast Cancer (TNBC) Yes	15 Participants n=5 Participants
HER 2 Status Positive	0 Participants n=5 Participants
HER 2 Status Negative	30 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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

Population: number of HER2 negative breast cancer patients that met criteria to be evaluable for this endpoint

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.

Outcome measures

Measure

Treatment (MEDI4736, Tremelimumab) n=27 Participants 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 Response Rate (ORR) in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab

4 participants

PRIMARY outcome

Timeframe: 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

Population: number of triple negative breast cancer patients that met criteria to be evaluable for this endpoint

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

Outcome measures

Measure

Treatment (MEDI4736, Tremelimumab) n=14 Participants 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 Response Rate (ORR) in Patients With Triple Negative Breast Cancer (TNBC) Treated With Durvalumab in Combination With Tremelimumab

4 participants

SECONDARY outcome

Timeframe: 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

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

Outcome measures

Measure	Treatment (MEDI4736, Tremelimumab) n=30 Participants 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
Toxicity in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab Grade 1 or 2 Adverse Event	27 participants
Toxicity in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab Grade 3 or 4 Adverse Event	12 participants
Toxicity in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab Grade 1 or 2 Serious Adverse Event	6 participants
Toxicity in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab Grade 3 or 4 Serious Adverse Event	7 participants

SECONDARY outcome

Timeframe: 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

Population: number of HER2 negative breast cancer patients that met criteria to be evaluable for this endpoint

OS is defined as the time from treatment initiation until death due to any cause

Outcome measures

Measure

Treatment (MEDI4736, Tremelimumab) n=27 Participants 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 Survival (OS) in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab

11.3 months Interval 7.16 to 36.6

SECONDARY outcome

Timeframe: 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

Population: number HER2 negative breast cancer patients that met criteria to be evaluable for this endpoint

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.)

Outcome measures

Measure

Treatment (MEDI4736, Tremelimumab) n=27 Participants 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

Progression Free Survival (PFS) in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab

4.86 months Interval 3.09 to 7.89

SECONDARY outcome

Timeframe: 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

Population: 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. number of patients HER2 negative breast cancer patients that met criteria to be evaluable for this endpoint

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

Outcome measures

Measure

Treatment (MEDI4736, Tremelimumab) n=27 Participants 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

Clinical Benefit Rate (CBR) in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab

5 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and at 2 months of treatment

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

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and at 2 months of treatment

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

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and at 2 months of treatment

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

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and at 2 months of treatment

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

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and at 2 months of treatment

To evaluate if tissue-based immunohistochemical expression of HLA predicts response to MEDI4736 in combination with tremelimumab

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and at 2 months of treatment

To evaluate if tissue-based immunohistochemical expression of Immune-related candidate gene signatures predicts response to MEDI4736 in combination with tremelimumab

Outcome measures

Outcome data not reported

POST_HOC outcome

Timeframe: 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

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.)

Outcome measures

Measure	Treatment (MEDI4736, Tremelimumab) n=30 Participants 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
Response in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab Complete Response	1 Participants
Response in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab Partial Response	3 Participants
Response in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab Stable Disease	4 Participants
Response in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab Progressive Disease	19 Participants
Response in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab Not evaluable	3 Participants

POST_HOC outcome

Timeframe: 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

Population: This includes patients who did not complete 2 months of treatment but would otherwise be evaluable for the endpoint

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.

Outcome measures

Measure

Treatment (MEDI4736, Tremelimumab) n=27 Participants 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 Response Rate (ORR) in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab (All Included)

4 participants

Adverse Events

Treatment (MEDI4736, Tremelimumab)

Serious events: 18 serious events

Other events: 30 other events

Deaths: 22 deaths

Serious adverse events

Measure	Treatment (MEDI4736, Tremelimumab) n=30 participants at risk 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
Nervous system disorders Confusion	6.7% 2/30 • Number of events 2 • 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.
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.3% 1/30 • Number of events 1 • 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.
Gastrointestinal disorders Vomiting	3.3% 1/30 • Number of events 1 • 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.
Hepatobiliary disorders Hepatitis	3.3% 1/30 • Number of events 1 • 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.
Cardiac disorders Myocarditis and Ventricular Tachycardia	3.3% 1/30 • Number of events 1 • 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.
Respiratory, thoracic and mediastinal disorders Shortness of breath	3.3% 1/30 • Number of events 1 • 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.
Infections and infestations Spontaneous bacterial peritonitis	3.3% 1/30 • Number of events 1 • 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.
Renal and urinary disorders Nephritis	3.3% 1/30 • Number of events 1 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Disease progression	3.3% 1/30 • Number of events 1 • 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.
Nervous system disorders Dizziness	3.3% 1/30 • Number of events 1 • 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.
General disorders Fever and chills	6.7% 2/30 • Number of events 2 • 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.
General disorders Fever	3.3% 1/30 • Number of events 1 • 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.
Gastrointestinal disorders Enteritis	3.3% 1/30 • Number of events 1 • 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.
Respiratory, thoracic and mediastinal disorders Respiratory failure	3.3% 1/30 • Number of events 2 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pseudoprogression	3.3% 1/30 • Number of events 1 • 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.
Infections and infestations Urosepsis	3.3% 1/30 • Number of events 1 • 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.

Other adverse events

Measure	Treatment (MEDI4736, Tremelimumab) n=30 participants at risk 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
Musculoskeletal and connective tissue disorders cancer related pain	3.3% 1/30 • 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.
Musculoskeletal and connective tissue disorders bilateral hand stiffness	3.3% 1/30 • 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.
Musculoskeletal and connective tissue disorders Neck pain	3.3% 1/30 • 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.
Musculoskeletal and connective tissue disorders Pain in extremity	13.3% 4/30 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) disease progression	3.3% 1/30 • 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.
Nervous system disorders Dizziness	3.3% 1/30 • 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.
Nervous system disorders Headache	10.0% 3/30 • 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.
Nervous system disorders Nervous system disorder NOS	3.3% 1/30 • 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.
Nervous system disorders Ptosis	3.3% 1/30 • 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.
Nervous system disorders Peripheral sensory neuropathy	6.7% 2/30 • 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.
Psychiatric disorders Anxiety	3.3% 1/30 • 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.
Psychiatric disorders Confusion	3.3% 1/30 • 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.
Psychiatric disorders Insomnia	10.0% 3/30 • 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.
Renal and urinary disorders Proteinuria	3.3% 1/30 • 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.
Renal and urinary disorders Urinary incontinence	3.3% 1/30 • 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.
Respiratory, thoracic and mediastinal disorders Cough	3.3% 1/30 • 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.
Respiratory, thoracic and mediastinal disorders Dyspnea	6.7% 2/30 • 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.
Respiratory, thoracic and mediastinal disorders Hypoxia	3.3% 1/30 • 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.
Respiratory, thoracic and mediastinal disorders Nasal congestion	3.3% 1/30 • 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.
Respiratory, thoracic and mediastinal disorders Pleural effusion	6.7% 2/30 • 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.
Respiratory, thoracic and mediastinal disorders Postnasal drip	3.3% 1/30 • 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.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	3.3% 1/30 • 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.
Respiratory, thoracic and mediastinal disorders Sore throat	3.3% 1/30 • 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.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	3.3% 1/30 • 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.
Skin and subcutaneous tissue disorders Dry skin	3.3% 1/30 • 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.
Skin and subcutaneous tissue disorders Pruritus	20.0% 6/30 • 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.
Skin and subcutaneous tissue disorders Rash maculo-papular	16.7% 5/30 • 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.
Skin and subcutaneous tissue disorders Skin ulceration	3.3% 1/30 • 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.
Vascular disorders Lymphedema	3.3% 1/30 • 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.
Vascular disorders Thromboembolic event	6.7% 2/30 • 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.
Blood and lymphatic system disorders Anemia	50.0% 15/30 • 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.
Cardiac disorders Palpitations	3.3% 1/30 • 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.
Cardiac disorders Sinus tachycardia	10.0% 3/30 • 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.
Ear and labyrinth disorders Ear pain	3.3% 1/30 • 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.
Endocrine disorders Hyperthyroidism	6.7% 2/30 • 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.
Endocrine disorders Hypothyroidism	13.3% 4/30 • 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.
Eye disorders Blurred vision	3.3% 1/30 • 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.
Eye disorders Floaters	3.3% 1/30 • 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.
Gastrointestinal disorders Abdominal pain	26.7% 8/30 • 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.
Gastrointestinal disorders Bloating	3.3% 1/30 • 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.
Gastrointestinal disorders Constipation	16.7% 5/30 • 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.
Gastrointestinal disorders Colitis	3.3% 1/30 • 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.
Gastrointestinal disorders Dental caries	3.3% 1/30 • 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.
Gastrointestinal disorders Diarrhea	20.0% 6/30 • 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.
Gastrointestinal disorders Dry mouth	3.3% 1/30 • 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.
Gastrointestinal disorders Dehydration	3.3% 1/30 • 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.
Gastrointestinal disorders Fecal incontinence	3.3% 1/30 • 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.
Gastrointestinal disorders Flatulence	3.3% 1/30 • 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.
Gastrointestinal disorders Gastroesophageal reflux disease	3.3% 1/30 • 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.
Gastrointestinal disorders Mucositis oral	3.3% 1/30 • 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.
Gastrointestinal disorders Nausea	20.0% 6/30 • 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.
Gastrointestinal disorders Oral pain	3.3% 1/30 • 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.
Gastrointestinal disorders Vomiting	13.3% 4/30 • 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.
General disorders Chills	3.3% 1/30 • 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.
General disorders Edema limbs	3.3% 1/30 • 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.
General disorders Fatigue	36.7% 11/30 • 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.
General disorders Fever	6.7% 2/30 • 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.
General disorders Flu like symptoms	3.3% 1/30 • 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.
General disorders Night sweats	3.3% 1/30 • 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.
General disorders Breast leison discomfort	3.3% 1/30 • 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.
General disorders Discomfort	3.3% 1/30 • 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.
General disorders Non-cardiac chest pain	6.7% 2/30 • 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.
General disorders Pain	13.3% 4/30 • 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.
Infections and infestations Pharyngitis	3.3% 1/30 • 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.
Infections and infestations Rash pustular	3.3% 1/30 • 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.
Infections and infestations Sinusitis	3.3% 1/30 • 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.
Infections and infestations Skin infection	3.3% 1/30 • 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.
Infections and infestations Upper respiratory infection	6.7% 2/30 • 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.
Infections and infestations Vaginal infection	3.3% 1/30 • 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.
Injury, poisoning and procedural complications Fall	3.3% 1/30 • 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.
Investigations Activated partial thromboplastin time prolonged	30.0% 9/30 • 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.
Investigations Alanine aminotransferase increased	30.0% 9/30 • 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.
Investigations Alkaline phosphatase increased	36.7% 11/30 • 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.
Investigations Aspartate aminotransferase increased	30.0% 9/30 • 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.
Investigations Blood bilirubin increased	23.3% 7/30 • 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.
Investigations Cardiac troponin I increased	3.3% 1/30 • 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.
Investigations Creatinine increased	10.0% 3/30 • 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.
Investigations Electrocardiogram QT corrected interval prolonged	3.3% 1/30 • 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.
Investigations GGT increased	26.7% 8/30 • 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.
Investigations Hemoglobin increased	3.3% 1/30 • 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.
Investigations INR increased	13.3% 4/30 • 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.
Investigations low GFR (clinically significant)	3.3% 1/30 • 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.
Investigations LV diastolic dysfunction	3.3% 1/30 • 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.
Investigations Lipase increased	20.0% 6/30 • 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.
Investigations Lymphocyte count decreased	43.3% 13/30 • 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.
Investigations Neutrophil count decreased	3.3% 1/30 • 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.
Investigations Platelet count decreased	23.3% 7/30 • 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.
Investigations Serum amylase increased	10.0% 3/30 • 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.
Investigations Weight gain	3.3% 1/30 • 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.
Investigations Weight loss	3.3% 1/30 • 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.
Investigations White blood cell decreased	13.3% 4/30 • 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.
Metabolism and nutrition disorders Anorexia	6.7% 2/30 • 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.
Metabolism and nutrition disorders Alkalosis	3.3% 1/30 • 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.
Metabolism and nutrition disorders Hypercalcemia	6.7% 2/30 • 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.
Metabolism and nutrition disorders Hyperglycemia	60.0% 18/30 • 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.
Metabolism and nutrition disorders Hyperkalemia	3.3% 1/30 • 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.
Metabolism and nutrition disorders Hypermagnesemia	13.3% 4/30 • 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.
Metabolism and nutrition disorders Hypernatremia	6.7% 2/30 • 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.
Metabolism and nutrition disorders Hypoalbuminemia	53.3% 16/30 • 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.
Metabolism and nutrition disorders Hypocalcemia	16.7% 5/30 • 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.
Metabolism and nutrition disorders Hypoglycemia	6.7% 2/30 • 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.
Metabolism and nutrition disorders Hypokalemia	13.3% 4/30 • 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.
Metabolism and nutrition disorders Hypomagnesemia	33.3% 10/30 • 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.
Metabolism and nutrition disorders Hyponatremia	20.0% 6/30 • 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.
Musculoskeletal and connective tissue disorders Arthralgia	3.3% 1/30 • 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.
Musculoskeletal and connective tissue disorders Back pain	10.0% 3/30 • 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.
Musculoskeletal and connective tissue disorders Bone pain	3.3% 1/30 • 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.
Musculoskeletal and connective tissue disorders joint stiffness (feet)	3.3% 1/30 • 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.
Musculoskeletal and connective tissue disorders generalized aches and pains	3.3% 1/30 • 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.

Additional Information

Ami Shah, MD

Northwestern University

Phone: 312 503 5488

Email: amishah@northwestern.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place