Trial Outcomes & Findings for Genetic Predictors of Benefit to Pembrolizumab (NCT NCT02710396)

Last Updated: 2023-07-24

Results Overview

Objective response to study treatment will be assessed by RECIST 1.1 by a study radiologist. Partial and complete responses will be confirmed by a repeat imaging occurring at least 4 weeks after the initial identification of response; unconfirmed responses will be considered stable or progressive disease dependent on results of the second CT scan. Durable clinical benefit (DCB) will be defined as stable disease (Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study), OR complete response (disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.), OR partial response (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) lasting longer than 6 months.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

19 participants

Primary outcome timeframe

Up to 2 years

Results posted on

2023-07-24

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort 1 Subjects will receive single agent pembrolizumab 200 mg IV will be administered every 3 weeks for up to 2 years. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2 (programmed cell death (PD) proteins). Pembrolizumab 200 mg will be administered IV every 3 weeks.	Cohort 2 Subjects will receive pembrolizumab 200 mg IV every 3 weeks for up to 2 years with 2 cycles of nab-paclitaxel and carboplatin administered with cycles 1 and 2. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2 (programmed cell death (PD) proteins). Pembrolizumab 200 mg will be administered IV every 3 weeks. Carboplatin: Carboplatin AUC (area under curve (AUC)) = 5 IV on day 1 every 3 weeks administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab. Nab-paclitaxel: Nab-paclitaxel 100 mg/m2 IV on days 1, 8 and 15 every 3 weeks administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab.
Overall Study STARTED	14	5
Overall Study COMPLETED	14	5
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Genetic Predictors of Benefit to Pembrolizumab

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 n=14 Participants Subjects will receive single agent pembrolizumab 200 mg IV will be administered every 3 weeks for up to 2 years. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2 (programmed cell death (PD) proteins). Pembrolizumab 200 mg will be administered IV every 3 weeks.	Cohort 2 n=5 Participants Subjects will receive pembrolizumab 200 mg IV every 3 weeks for up to 2 years with 2 cycles of nab-paclitaxel and carboplatin administered with cycles 1 and 2. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2 (programmed cell death (PD) proteins). Pembrolizumab 200 mg will be administered IV every 3 weeks. Carboplatin: Carboplatin AUC (area under curve (AUC)) = 5 IV on day 1 every 3 weeks administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab. Nab-paclitaxel: Nab-paclitaxel 100 mg/m2 IV on days 1, 8 and 15 every 3 weeks administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab.	Cohort 3 Subject will receive pembrolizumab 200 mg IV every 3 weeks for up to 2 years with 2 cycles of pemetrexed and carboplatin administered with cycles 1 and 2. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2 (programmed cell death (PD) proteins). Pembrolizumab 200 mg will be administered IV every 3 weeks. Carboplatin: Carboplatin AUC (area under curve (AUC)) = 5 IV on day 1 every 3 weeks administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab. Pemetrexed: Pemetrexed 500 mg/m2 IV administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab.	Total n=19 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Age, Categorical >=65 years	13 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	15 Participants n=4 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	8 Participants n=4 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	11 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	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	12 Participants n=4 Participants
Race (NIH/OMB) More than one race	4 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	14 participants n=5 Participants	5 participants n=7 Participants	—	19 participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 2 years

Population: Zero analyzed in Cohort 3 as zero subjects participated in Cohort 3.

Outcome measures

Outcome measures
Measure	Cohort 1 n=14 Participants Subjects will receive single agent pembrolizumab 200 mg IV will be administered every 3 weeks for up to 2 years. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2 (programmed cell death (PD) proteins). Pembrolizumab 200 mg will be administered IV every 3 weeks.	Cohort 2 n=5 Participants Subjects will receive pembrolizumab 200 mg IV every 3 weeks for up to 2 years with 2 cycles of nab-paclitaxel and carboplatin administered with cycles 1 and 2. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2 (programmed cell death (PD) proteins). Pembrolizumab 200 mg will be administered IV every 3 weeks. Carboplatin: Carboplatin AUC (area under curve (AUC)) = 5 IV on day 1 every 3 weeks administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab. Nab-paclitaxel: Nab-paclitaxel 100 mg/m2 IV on days 1, 8 and 15 every 3 weeks administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab.	Cohort 3 Subject will receive pembrolizumab 200 mg IV every 3 weeks for up to 2 years with 2 cycles of pemetrexed and carboplatin administered with cycles 1 and 2. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2 (programmed cell death (PD) proteins). Pembrolizumab 200 mg will be administered IV every 3 weeks. Carboplatin: Carboplatin AUC (area under curve (AUC)) = 5 IV on day 1 every 3 weeks administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab. Pemetrexed: Pemetrexed 500 mg/m2 IV administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab.
Number of Subjects With NSCLC Who Achieved DCB	3 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 2 years

Population: Zero analyzed in Cohort 3 as zero subjects participated in Cohort 3.

ORR is defined as participants with a partial (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) or complete response (Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm) as assessed by RECIST 1.1 criteria.

Outcome measures

Outcome measures
Measure	Cohort 1 n=14 Participants Subjects will receive single agent pembrolizumab 200 mg IV will be administered every 3 weeks for up to 2 years. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2 (programmed cell death (PD) proteins). Pembrolizumab 200 mg will be administered IV every 3 weeks.	Cohort 2 n=5 Participants Subjects will receive pembrolizumab 200 mg IV every 3 weeks for up to 2 years with 2 cycles of nab-paclitaxel and carboplatin administered with cycles 1 and 2. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2 (programmed cell death (PD) proteins). Pembrolizumab 200 mg will be administered IV every 3 weeks. Carboplatin: Carboplatin AUC (area under curve (AUC)) = 5 IV on day 1 every 3 weeks administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab. Nab-paclitaxel: Nab-paclitaxel 100 mg/m2 IV on days 1, 8 and 15 every 3 weeks administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab.	Cohort 3 Subject will receive pembrolizumab 200 mg IV every 3 weeks for up to 2 years with 2 cycles of pemetrexed and carboplatin administered with cycles 1 and 2. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2 (programmed cell death (PD) proteins). Pembrolizumab 200 mg will be administered IV every 3 weeks. Carboplatin: Carboplatin AUC (area under curve (AUC)) = 5 IV on day 1 every 3 weeks administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab. Pemetrexed: Pemetrexed 500 mg/m2 IV administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab.
Objective Response Rate (ORR)	4 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 2 years

Population: Zero analyzed in Cohort 3 as zero subjects participated in Cohort 3.

The length of time from treatment initiation to progression of 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. The appearance of one or more new lesions is also considered progression) as assessed by RECIST 1.1.

Outcome measures

Outcome measures
Measure	Cohort 1 n=14 Participants Subjects will receive single agent pembrolizumab 200 mg IV will be administered every 3 weeks for up to 2 years. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2 (programmed cell death (PD) proteins). Pembrolizumab 200 mg will be administered IV every 3 weeks.	Cohort 2 n=5 Participants Subjects will receive pembrolizumab 200 mg IV every 3 weeks for up to 2 years with 2 cycles of nab-paclitaxel and carboplatin administered with cycles 1 and 2. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2 (programmed cell death (PD) proteins). Pembrolizumab 200 mg will be administered IV every 3 weeks. Carboplatin: Carboplatin AUC (area under curve (AUC)) = 5 IV on day 1 every 3 weeks administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab. Nab-paclitaxel: Nab-paclitaxel 100 mg/m2 IV on days 1, 8 and 15 every 3 weeks administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab.	Cohort 3 Subject will receive pembrolizumab 200 mg IV every 3 weeks for up to 2 years with 2 cycles of pemetrexed and carboplatin administered with cycles 1 and 2. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2 (programmed cell death (PD) proteins). Pembrolizumab 200 mg will be administered IV every 3 weeks. Carboplatin: Carboplatin AUC (area under curve (AUC)) = 5 IV on day 1 every 3 weeks administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab. Pemetrexed: Pemetrexed 500 mg/m2 IV administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab.
Progression Free Survival (PFS)	4.80 months Interval 1.61 to 11.53	3.94 months Interval 1.38 to 23.49	—

SECONDARY outcome

Timeframe: Up to 28 months

Population: Zero analyzed in Cohort 3 as zero subjects participated in Cohort 3.

The length of time from the start of treatment to death.

Outcome measures

Outcome measures
Measure	Cohort 1 n=14 Participants Subjects will receive single agent pembrolizumab 200 mg IV will be administered every 3 weeks for up to 2 years. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2 (programmed cell death (PD) proteins). Pembrolizumab 200 mg will be administered IV every 3 weeks.	Cohort 2 n=5 Participants Subjects will receive pembrolizumab 200 mg IV every 3 weeks for up to 2 years with 2 cycles of nab-paclitaxel and carboplatin administered with cycles 1 and 2. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2 (programmed cell death (PD) proteins). Pembrolizumab 200 mg will be administered IV every 3 weeks. Carboplatin: Carboplatin AUC (area under curve (AUC)) = 5 IV on day 1 every 3 weeks administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab. Nab-paclitaxel: Nab-paclitaxel 100 mg/m2 IV on days 1, 8 and 15 every 3 weeks administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab.	Cohort 3 Subject will receive pembrolizumab 200 mg IV every 3 weeks for up to 2 years with 2 cycles of pemetrexed and carboplatin administered with cycles 1 and 2. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2 (programmed cell death (PD) proteins). Pembrolizumab 200 mg will be administered IV every 3 weeks. Carboplatin: Carboplatin AUC (area under curve (AUC)) = 5 IV on day 1 every 3 weeks administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab. Pemetrexed: Pemetrexed 500 mg/m2 IV administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab.
Overall Survival (OS)	14.06 Months Interval 5.95 to 20.37	23.49 Months Interval 1.38 to 27.63	—

Adverse Events

Cohort 1

Serious events: 10 serious events

Other events: 13 other events

Deaths: 12 deaths

Cohort 2

Serious events: 5 serious events

Other events: 5 other events

Deaths: 4 deaths

Cohort 3

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Catherine Shu

Columbia University Herbert Irving Comprehensive Cancer Center

Phone: 212 305 3997

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort 1 n=14 participants at risk Subjects will receive single agent pembrolizumab 200 mg IV will be administered every 3 weeks for up to 2 years. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2 (programmed cell death (PD) proteins). Pembrolizumab 200 mg will be administered IV every 3 weeks.	Cohort 2 n=5 participants at risk Subjects will receive pembrolizumab 200 mg IV every 3 weeks for up to 2 years with 2 cycles of nab-paclitaxel and carboplatin administered with cycles 1 and 2. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2 (programmed cell death (PD) proteins). Pembrolizumab 200 mg will be administered IV every 3 weeks. Carboplatin: Carboplatin AUC (area under curve (AUC)) = 5 IV on day 1 every 3 weeks administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab. Nab-paclitaxel: Nab-paclitaxel 100 mg/m2 IV on days 1, 8 and 15 every 3 weeks administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab.	Cohort 3 Subject will receive pembrolizumab 200 mg IV every 3 weeks for up to 2 years with 2 cycles of pemetrexed and carboplatin administered with cycles 1 and 2. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2 (programmed cell death (PD) proteins). Pembrolizumab 200 mg will be administered IV every 3 weeks. Carboplatin: Carboplatin AUC (area under curve (AUC)) = 5 IV on day 1 every 3 weeks administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab. Pemetrexed: Pemetrexed 500 mg/m2 IV administered for 2 cycles concurrently with cycles 1 and 2 of pembrolizumab.
Gastrointestinal disorders Abdominal Pain	7.1% 1/14 • Up to 28 months Zero subjects participated in Cohort 3.	20.0% 1/5 • Up to 28 months Zero subjects participated in Cohort 3.	— 0/0 • Up to 28 months Zero subjects participated in Cohort 3.
Gastrointestinal disorders Colitis	7.1% 1/14 • Up to 28 months Zero subjects participated in Cohort 3.	0.00% 0/5 • Up to 28 months Zero subjects participated in Cohort 3.	— 0/0 • Up to 28 months Zero subjects participated in Cohort 3.
Psychiatric disorders Delirium	7.1% 1/14 • Up to 28 months Zero subjects participated in Cohort 3.	0.00% 0/5 • Up to 28 months Zero subjects participated in Cohort 3.	— 0/0 • Up to 28 months Zero subjects participated in Cohort 3.
Nervous system disorders Dysphasia	7.1% 1/14 • Up to 28 months Zero subjects participated in Cohort 3.	0.00% 0/5 • Up to 28 months Zero subjects participated in Cohort 3.	— 0/0 • Up to 28 months Zero subjects participated in Cohort 3.
Respiratory, thoracic and mediastinal disorders Dyspnea	7.1% 1/14 • Up to 28 months Zero subjects participated in Cohort 3.	0.00% 0/5 • Up to 28 months Zero subjects participated in Cohort 3.	— 0/0 • Up to 28 months Zero subjects participated in Cohort 3.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	14.3% 2/14 • Up to 28 months Zero subjects participated in Cohort 3.	0.00% 0/5 • Up to 28 months Zero subjects participated in Cohort 3.	— 0/0 • Up to 28 months Zero subjects participated in Cohort 3.
Renal and urinary disorders Hematuria	7.1% 1/14 • Up to 28 months Zero subjects participated in Cohort 3.	0.00% 0/5 • Up to 28 months Zero subjects participated in Cohort 3.	— 0/0 • Up to 28 months Zero subjects participated in Cohort 3.
Metabolism and nutrition disorders Hyperglycemia	7.1% 1/14 • Up to 28 months Zero subjects participated in Cohort 3.	0.00% 0/5 • Up to 28 months Zero subjects participated in Cohort 3.	— 0/0 • Up to 28 months Zero subjects participated in Cohort 3.
Gastrointestinal disorders Lower gastrointestinal hemorrhage	7.1% 1/14 • Up to 28 months Zero subjects participated in Cohort 3.	0.00% 0/5 • Up to 28 months Zero subjects participated in Cohort 3.	— 0/0 • Up to 28 months Zero subjects participated in Cohort 3.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified	21.4% 3/14 • Up to 28 months Zero subjects participated in Cohort 3.	0.00% 0/5 • Up to 28 months Zero subjects participated in Cohort 3.	— 0/0 • Up to 28 months Zero subjects participated in Cohort 3.
Musculoskeletal and connective tissue disorders Pain in extremity	7.1% 1/14 • Up to 28 months Zero subjects participated in Cohort 3.	0.00% 0/5 • Up to 28 months Zero subjects participated in Cohort 3.	— 0/0 • Up to 28 months Zero subjects participated in Cohort 3.
Respiratory, thoracic and mediastinal disorders Pleural effusion	7.1% 1/14 • Up to 28 months Zero subjects participated in Cohort 3.	0.00% 0/5 • Up to 28 months Zero subjects participated in Cohort 3.	— 0/0 • Up to 28 months Zero subjects participated in Cohort 3.
Respiratory, thoracic and mediastinal disorders Pneumothorax	7.1% 1/14 • Up to 28 months Zero subjects participated in Cohort 3.	20.0% 1/5 • Up to 28 months Zero subjects participated in Cohort 3.	— 0/0 • Up to 28 months Zero subjects participated in Cohort 3.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/14 • Up to 28 months Zero subjects participated in Cohort 3.	20.0% 1/5 • Up to 28 months Zero subjects participated in Cohort 3.	— 0/0 • Up to 28 months Zero subjects participated in Cohort 3.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	7.1% 1/14 • Up to 28 months Zero subjects participated in Cohort 3.	0.00% 0/5 • Up to 28 months Zero subjects participated in Cohort 3.	— 0/0 • Up to 28 months Zero subjects participated in Cohort 3.
Infections and infestations Sepsis	7.1% 1/14 • Up to 28 months Zero subjects participated in Cohort 3.	0.00% 0/5 • Up to 28 months Zero subjects participated in Cohort 3.	— 0/0 • Up to 28 months Zero subjects participated in Cohort 3.
Infections and infestations Urinary tract infection	7.1% 1/14 • Up to 28 months Zero subjects participated in Cohort 3.	0.00% 0/5 • Up to 28 months Zero subjects participated in Cohort 3.	— 0/0 • Up to 28 months Zero subjects participated in Cohort 3.
Renal and urinary disorders Acute kidney injury	0.00% 0/14 • Up to 28 months Zero subjects participated in Cohort 3.	20.0% 1/5 • Up to 28 months Zero subjects participated in Cohort 3.	— 0/0 • Up to 28 months Zero subjects participated in Cohort 3.
Infections and infestations Bronchial infection	0.00% 0/14 • Up to 28 months Zero subjects participated in Cohort 3.	20.0% 1/5 • Up to 28 months Zero subjects participated in Cohort 3.	— 0/0 • Up to 28 months Zero subjects participated in Cohort 3.
Injury, poisoning and procedural complications Fracture	0.00% 0/14 • Up to 28 months Zero subjects participated in Cohort 3.	20.0% 1/5 • Up to 28 months Zero subjects participated in Cohort 3.	— 0/0 • Up to 28 months Zero subjects participated in Cohort 3.
Infections and infestations Lung infection	0.00% 0/14 • Up to 28 months Zero subjects participated in Cohort 3.	20.0% 1/5 • Up to 28 months Zero subjects participated in Cohort 3.	— 0/0 • Up to 28 months Zero subjects participated in Cohort 3.