Trial Outcomes & Findings for Pembrolizumab and Binimetinib in Treating Patients With Locally Advanced or Metastatic Triple Negative Breast Cancer (NCT NCT03106415)

Last Updated: 2025-06-27

Results Overview

Will be assessed by Common Terminology Criteria for Adverse Events version 4.0. Safety/adverse events data will be tabulated, including adverse events of all grades.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

23 participants

Primary outcome timeframe

35 days

Results posted on

2025-06-27

Participant Flow

Participant milestones

Participant milestones
Measure	Phase 1 Dose Level 0 Patients receive 45mg binimetinib PO BID on days 1-14 of cycle 1 and on days 1-21 of cycle 2 and subsequent cycles. Beginning cycle 2, patients also receive 200mg pembrolizumab IV over 30 minutes on day 1. Cycle 1 equals 14 days. Cycles 2 and beyond repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Phase 1 Dose Level -1 Patients receive 30mg binimetinib PO BID on days 1-14 of cycle 1 and on days 1-21 of cycle 2 and subsequent cycles. Beginning cycle 2, patients also receive 200mg pembrolizumab IV over 30 minutes on day 1. Cycle 1 equals 14 days. Cycles 2 and beyond repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Phase 2 Patients receive 30mg binimetinib PO BID on days 1-14 of cycle 1 and on days 1-21 of cycle 2 and subsequent cycles. Beginning cycle 2, patients also receive 200mg pembrolizumab IV over 30 minutes on day 1. Cycle 1 equals 14 days. Cycles 2 and beyond repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Phase 1 STARTED	5	8	0
Phase 1 COMPLETED	3	6	0
Phase 1 NOT COMPLETED	2	2	0
Phase 2 STARTED	0	8	10
Phase 2 COMPLETED	0	8	10
Phase 2 NOT COMPLETED	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1 Dose Level 0 Patients receive 45mg binimetinib PO BID on days 1-14 of cycle 1 and on days 1-21 of cycle 2 and subsequent cycles. Beginning cycle 2, patients also receive 200mg pembrolizumab IV over 30 minutes on day 1. Cycle 1 equals 14 days. Cycles 2 and beyond repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Phase 1 Dose Level -1 Patients receive 30mg binimetinib PO BID on days 1-14 of cycle 1 and on days 1-21 of cycle 2 and subsequent cycles. Beginning cycle 2, patients also receive 200mg pembrolizumab IV over 30 minutes on day 1. Cycle 1 equals 14 days. Cycles 2 and beyond repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Phase 1 Withdrawal by Subject	1	0
Phase 1 Adverse Event	1	1
Phase 1 Protocol Violation	0	1

Baseline Characteristics

Pembrolizumab and Binimetinib in Treating Patients With Locally Advanced or Metastatic Triple Negative Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1 Dose Level 0 n=5 Participants Patients receive 45mg binimetinib PO BID on days 1-14 of cycle 1 and on days 1-21 of cycle 2 and subsequent cycles. Beginning cycle 2, patients also receive 200mg pembrolizumab IV over 30 minutes on day 1. Cycle 1 equals 14 days. Cycles 2 and beyond repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Phase 1 Dose Level -1 n=8 Participants Patients receive 30mg binimetinib PO BID on days 1-14 of cycle 1 and on days 1-21 of cycle 2 and subsequent cycles. Beginning cycle 2, patients also receive 200mg pembrolizumab IV over 30 minutes on day 1. Cycle 1 equals 14 days. Cycles 2 and beyond repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Phase 2 n=10 Participants Patients receive 30mg binimetinib PO BID on days 1-14 of cycle 1 and on days 1-21 of cycle 2 and subsequent cycles. Beginning cycle 2, patients also receive 200mg pembrolizumab IV over 30 minutes on day 1. Cycle 1 equals 14 days. Cycles 2 and beyond repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Total n=23 Participants Total of all reporting groups
Age, Continuous	63 years n=5 Participants	62 years n=7 Participants	54.5 years n=5 Participants	58 years n=4 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	8 Participants n=7 Participants	10 Participants n=5 Participants	23 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants	21 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	8 Participants n=4 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants	12 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants

PRIMARY outcome

Timeframe: 35 days

Population: All patients treated per protocol and evaluated for dose limiting toxicities.

Will be assessed by Common Terminology Criteria for Adverse Events version 4.0. Safety/adverse events data will be tabulated, including adverse events of all grades.

Outcome measures

Outcome measures
Measure	Phase 1 Dose Level 0 n=3 Participants Patients receive 45mg binimetinib PO BID on days 1-14 of cycle 1 and on days 1-21 of cycle 2 and subsequent cycles. Beginning cycle 2, patients also receive 200mg pembrolizumab IV over 30 minutes on day 1. Cycle 1 equals 14 days. Cycles 2 and beyond repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Phase 1 Dose Level -1 n=6 Participants Patients receive 30mg binimetinib PO BID on days 1-14 of cycle 1 and on days 1-21 of cycle 2 and subsequent cycles. Beginning cycle 2, patients also receive 200mg pembrolizumab IV over 30 minutes on day 1. Cycle 1 equals 14 days. Cycles 2 and beyond repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Maximum Tolerated Dose (MTD) of Pembrolizumab in Combination With Binimetinib Using the Standard 3+3 Design (Phase I) Experienced Dose Limiting Toxicity	2 Participants	0 Participants
Maximum Tolerated Dose (MTD) of Pembrolizumab in Combination With Binimetinib Using the Standard 3+3 Design (Phase I) No Dose Limiting toxicity	1 Participants	6 Participants

PRIMARY outcome

Timeframe: 3 years

Population: Phase 1 dose level -1 patients are included with phase 2 patients in order to increase the strength of analysis.

Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST). Will utilize Simon's Two-Stage Optimal Design to test the null hypothesis. Will be estimated using the approach of Jung and Kim. The 90% lower confidence bound will be calculated using the approach of Koyama and Chen. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	Phase 1 Dose Level 0 n=18 Participants Patients receive 45mg binimetinib PO BID on days 1-14 of cycle 1 and on days 1-21 of cycle 2 and subsequent cycles. Beginning cycle 2, patients also receive 200mg pembrolizumab IV over 30 minutes on day 1. Cycle 1 equals 14 days. Cycles 2 and beyond repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Phase 1 Dose Level -1 Patients receive 30mg binimetinib PO BID on days 1-14 of cycle 1 and on days 1-21 of cycle 2 and subsequent cycles. Beginning cycle 2, patients also receive 200mg pembrolizumab IV over 30 minutes on day 1. Cycle 1 equals 14 days. Cycles 2 and beyond repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Objective Response Rate (ORR) as (Phase II)	.304 Proportion of participants Interval 0.122 to 0.473	—

SECONDARY outcome

Timeframe: Up to 3 years

Population: Only patients treated at the maximum tolerated dose level 0f -1 are evaluable for this phase 2 response analysis. Phase 1 dose level -1 patients and Phase 2 dose level -1 patients were combined for this analysis. Patients treated on other dose levels explored during the phase 1 portion, such as dose level 0, are excluded.

The Overall Response Rate, ORR, is defined as the proportion of patients with a response per irRECIST. It will be estimated as a binomial proportion with a 2-sided 95% confidence intervals. Baseline tumor infiltrating lymphocyte (TILs) and percent change in TILs from baseline will be summarized. Logistic regression models will be used to assess the correlation between these biomarkers and ORR in order to assess their prognostic significance.

Outcome measures

Outcome measures
Measure	Phase 1 Dose Level 0 n=18 Participants Patients receive 45mg binimetinib PO BID on days 1-14 of cycle 1 and on days 1-21 of cycle 2 and subsequent cycles. Beginning cycle 2, patients also receive 200mg pembrolizumab IV over 30 minutes on day 1. Cycle 1 equals 14 days. Cycles 2 and beyond repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Phase 1 Dose Level -1 Patients receive 30mg binimetinib PO BID on days 1-14 of cycle 1 and on days 1-21 of cycle 2 and subsequent cycles. Beginning cycle 2, patients also receive 200mg pembrolizumab IV over 30 minutes on day 1. Cycle 1 equals 14 days. Cycles 2 and beyond repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ORR by Immune-related RECIST Criteria (irRECIST)	0.278 proportion of participants Interval 0.097 to 0.535	—

SECONDARY outcome

Timeframe: The time from study enrollment to date of progression, assessed up to 3 years

Population: All treated and evaluable patients were analyzed by dose level.

Patients who are alive (including those lost to follow-up) at the time of data analysis will be censored at the last known alive date. A Kaplan-Meier curve will be used to summarize the PFS experience of this patient cohort. Cox Proportional Hazard models will be used to assess baseline TILs and percent change in TILs from baseline and their correlation with PFS. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Outcome measures
Measure	Phase 1 Dose Level 0 n=4 Participants Patients receive 45mg binimetinib PO BID on days 1-14 of cycle 1 and on days 1-21 of cycle 2 and subsequent cycles. Beginning cycle 2, patients also receive 200mg pembrolizumab IV over 30 minutes on day 1. Cycle 1 equals 14 days. Cycles 2 and beyond repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Phase 1 Dose Level -1 n=18 Participants Patients receive 30mg binimetinib PO BID on days 1-14 of cycle 1 and on days 1-21 of cycle 2 and subsequent cycles. Beginning cycle 2, patients also receive 200mg pembrolizumab IV over 30 minutes on day 1. Cycle 1 equals 14 days. Cycles 2 and beyond repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Progression Free Survival (PFS)	2.43 Months Interval 0.49 to Due to lack of events the upper limit was not reached	7.92 Months Interval 3.88 to Due to lack of events the upper limit was not reached

SECONDARY outcome

Timeframe: The time from study enrollment to death attributable to any cause, assessed up to 3 years

Population: All treated and evaluable patients were analyzed by dose level.

Outcome measures

Outcome measures
Measure	Phase 1 Dose Level 0 n=4 Participants Patients receive 45mg binimetinib PO BID on days 1-14 of cycle 1 and on days 1-21 of cycle 2 and subsequent cycles. Beginning cycle 2, patients also receive 200mg pembrolizumab IV over 30 minutes on day 1. Cycle 1 equals 14 days. Cycles 2 and beyond repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Phase 1 Dose Level -1 n=18 Participants Patients receive 30mg binimetinib PO BID on days 1-14 of cycle 1 and on days 1-21 of cycle 2 and subsequent cycles. Beginning cycle 2, patients also receive 200mg pembrolizumab IV over 30 minutes on day 1. Cycle 1 equals 14 days. Cycles 2 and beyond repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Survival (OS)	7.03 Months Interval 0.49 to Due to lack of events the upper limit was not reached	33.18 Months Interval 11.24 to Due to lack of events the upper limit was not reached

Adverse Events

Phase 1 Dose Level 0

Serious events: 1 serious events

Other events: 3 other events

Deaths: 5 deaths

Phase 1 Dose Level -1

Serious events: 3 serious events

Other events: 8 other events

Deaths: 4 deaths

Phase 2

Serious events: 5 serious events

Other events: 10 other events

Deaths: 7 deaths

Serious adverse events

Other adverse events

Additional Information

Saranya Chumsri MD

Mayo Clinic

Phone: 904-953-2000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Phase 1 Dose Level 0 n=4 participants at risk Patients receive 45mg binimetinib PO BID on days 1-14 of cycle 1 and on days 1-21 of cycle 2 and subsequent cycles. Beginning cycle 2, patients also receive 200mg pembrolizumab IV over 30 minutes on day 1. Cycle 1 equals 14 days. Cycles 2 and beyond repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Phase 1 Dose Level -1 n=8 participants at risk Patients receive 30mg binimetinib PO BID on days 1-14 of cycle 1 and on days 1-21 of cycle 2 and subsequent cycles. Beginning cycle 2, patients also receive 200mg pembrolizumab IV over 30 minutes on day 1. Cycle 1 equals 14 days. Cycles 2 and beyond repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Phase 2 n=10 participants at risk Patients receive 30mg binimetinib PO BID on days 1-14 of cycle 1 and on days 1-21 of cycle 2 and subsequent cycles. Beginning cycle 2, patients also receive 200mg pembrolizumab IV over 30 minutes on day 1. Cycle 1 equals 14 days. Cycles 2 and beyond repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	0.00% 0/4 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	0.00% 0/8 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	10.0% 1/10 • Number of events 1 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events
Endocrine disorders Hypothyroidism	0.00% 0/4 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	0.00% 0/8 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	10.0% 1/10 • Number of events 1 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events
Gastrointestinal disorders Colonic hemorrhage	0.00% 0/4 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	12.5% 1/8 • Number of events 1 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	0.00% 0/10 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/4 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	0.00% 0/8 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	10.0% 1/10 • Number of events 1 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events
Infections and infestations Lung infection	0.00% 0/4 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	0.00% 0/8 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	10.0% 1/10 • Number of events 2 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events
Infections and infestations Sepsis	0.00% 0/4 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	0.00% 0/8 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	10.0% 1/10 • Number of events 2 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events
Infections and infestations Urinary tract infection	0.00% 0/4 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	0.00% 0/8 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	10.0% 1/10 • Number of events 1 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events
Investigations Aspartate aminotransferase increased	0.00% 0/4 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	12.5% 1/8 • Number of events 1 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	0.00% 0/10 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events
Investigations Neutrophil count decreased	0.00% 0/4 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	0.00% 0/8 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	20.0% 2/10 • Number of events 2 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/4 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	12.5% 1/8 • Number of events 1 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	0.00% 0/10 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/4 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	12.5% 1/8 • Number of events 1 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	0.00% 0/10 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, mal, uncpec - Oth spec	25.0% 1/4 • Number of events 1 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	0.00% 0/8 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	0.00% 0/10 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events
Renal and urinary disorders Acute kidney injury	0.00% 0/4 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	0.00% 0/8 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	10.0% 1/10 • Number of events 2 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events
Respiratory, thoracic and mediastinal disorders Dyspnea	25.0% 1/4 • Number of events 1 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	0.00% 0/8 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	20.0% 2/10 • Number of events 3 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/4 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	0.00% 0/8 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	10.0% 1/10 • Number of events 1 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/4 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	0.00% 0/8 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	10.0% 1/10 • Number of events 1 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/4 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	0.00% 0/8 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	10.0% 1/10 • Number of events 1 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/4 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	0.00% 0/8 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	10.0% 1/10 • Number of events 1 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events
Skin and subcutaneous tissue disorders Skin and subcut tissue disord - Oth spec	0.00% 0/4 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	0.00% 0/8 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	10.0% 1/10 • Number of events 1 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events
Vascular disorders Hypertension	0.00% 0/4 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	12.5% 1/8 • Number of events 1 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	0.00% 0/10 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events
Vascular disorders Thromboembolic event	0.00% 0/4 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	0.00% 0/8 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events	10.0% 1/10 • Number of events 1 • Adverse events were followed for 3 years and mortality was followed for 4.5 years One Phase 1 Dose Level 0 patient was never treated or assessed for adverse events