Trial Outcomes & Findings for REGN2810 (Anti-PD-1 Antibody), Platinum-based Doublet Chemotherapy, and Ipilimumab (Anti-CTLA-4 Antibody) Versus Pembrolizumab Monotherapy in Patients With Lung Cancer (NCT NCT03515629)

Last Updated: 2022-11-16

Results Overview

Per protocol, the final analysis of PFS was to be performed after observing 142 PFS events in the pembrolizumab treatment arm. PFS was not assessed due to insufficient data collected.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

5 participants

Primary outcome timeframe

Up to 32 months

Results posted on

2022-11-16

Participant Flow

This study was conducted at 3 centers that randomized 5 participants in the United States, Lithuania, and Italy.

Due to program de-prioritization, the sponsor decided to cease enrollment at which time only 5 participants were randomized to 2 of 3 treatment arms (i.e., no participants were randomized to receive pembrolizumab).

Participant milestones

Participant milestones
Measure	Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W Cemiplimab was administered at 350 mg as an intravenous (IV) infusion every 3 weeks (Q3W) for 108 weeks in combination with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.	Cemiplimab 350 mg Q3W + Chemotherapy + Ipilimumab 50 mg Q6W Cemiplimab was administered at 350 mg as an IV infusion Q3W for 108 weeks in combination with platinum-based doublet chemotherapy administered IV Q3W for 2 cycles and with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.
Overall Study STARTED	3	2
Overall Study COMPLETED	1	1
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Pembrolizumab Due to ceasing enrollment early, no participants were randomized to receive pembrolizumab.	Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W Cemiplimab was administered at 350 mg as an intravenous (IV) infusion every 3 weeks (Q3W) for 108 weeks in combination with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.	Cemiplimab 350 mg Q3W + Chemotherapy + Ipilimumab 50 mg Q6W Cemiplimab was administered at 350 mg as an IV infusion Q3W for 108 weeks in combination with platinum-based doublet chemotherapy administered IV Q3W for 2 cycles and with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.
Overall Study Death	0	1	1
Overall Study Progressive disease	0	1	0

Baseline Characteristics

REGN2810 (Anti-PD-1 Antibody), Platinum-based Doublet Chemotherapy, and Ipilimumab (Anti-CTLA-4 Antibody) Versus Pembrolizumab Monotherapy in Patients With Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W n=3 Participants Cemiplimab was administered at 350 mg as an intravenous (IV) infusion every 3 weeks (Q3W) for 108 weeks in combination with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.	Cemiplimab 350 mg Q3W + Chemotherapy + Ipilimumab 50 mg Q6W n=2 Participants Cemiplimab was administered at 350 mg as an IV infusion Q3W for 108 weeks in combination with platinum-based doublet chemotherapy administered IV Q3W for 2 cycles and with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.	Total n=5 Participants Total of all reporting groups
Age, Continuous	61.7 Years STANDARD_DEVIATION 9.29 • n=5 Participants	56.5 Years STANDARD_DEVIATION 4.95 • n=7 Participants	59.6 Years STANDARD_DEVIATION 7.57 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 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
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 32 months

Population: PFS was not assessed due to insufficient data collected.

Per protocol, the final analysis of PFS was to be performed after observing 142 PFS events in the pembrolizumab treatment arm. PFS was not assessed due to insufficient data collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 32 months

Population: OS was not assessed due to insufficient data collected.

Per protocol, if the final analysis of PFS was statistically significant for both cemiplimab combination therapy versus pembrolizumab treatment, the analysis of OS for cemiplimab combinations-versus-pembrolizumab comparison was to be performed at the time of PFS analysis, 12 months, and 18 months after analysis of PFS using the same method as used in the analysis of PFS.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 32 months

Population: ORR was not assessed due to insufficient data collected.

Per protocol, the ORR for each cemiplimab combination-versus-pembrolizumab comparison was to be analyzed using the Cochran-Mantel-Haenszel test stratified by histological status (non-squamous versus squamous).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 32 months

Population: Safety analysis set (SAF), defined as all enrolled participants who received any amount of study treatment

Outcome measures

Outcome measures
Measure	Pembrolizumab n=3 Participants Due to ceasing enrollment early, no participants were randomized to receive pembrolizumab.	Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W n=2 Participants Cemiplimab was administered at 350 mg as an intravenous (IV) infusion every 3 weeks (Q3W) for 108 weeks in combination with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.	Cemiplimab 350 mg Q3W + Chemotherapy + Ipilimumab 50 mg Q6W Cemiplimab was administered at 350 mg as an IV infusion Q3W for 108 weeks in combination with platinum-based doublet chemotherapy administered IV Q3W for 2 cycles and with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.
Number of Treatment-Emergent Adverse Events (TEAEs)	68 Events	91 Events	—

SECONDARY outcome

Timeframe: Up to 32 months

Population: Safety analysis set (SAF), defined as all enrolled participants who received any amount of study treatment.

Outcome measures

Outcome measures
Measure	Pembrolizumab n=3 Participants Due to ceasing enrollment early, no participants were randomized to receive pembrolizumab.	Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W n=2 Participants Cemiplimab was administered at 350 mg as an intravenous (IV) infusion every 3 weeks (Q3W) for 108 weeks in combination with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.	Cemiplimab 350 mg Q3W + Chemotherapy + Ipilimumab 50 mg Q6W Cemiplimab was administered at 350 mg as an IV infusion Q3W for 108 weeks in combination with platinum-based doublet chemotherapy administered IV Q3W for 2 cycles and with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.
Number of Participants With Dose-Limiting Toxicities (DLTs)	0 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Up to 32 months

Population: Safety analysis set (SAF), defined as all enrolled participants who received any amount of study treatment

Outcome measures

Outcome measures
Measure	Pembrolizumab n=3 Participants Due to ceasing enrollment early, no participants were randomized to receive pembrolizumab.	Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W n=2 Participants Cemiplimab was administered at 350 mg as an intravenous (IV) infusion every 3 weeks (Q3W) for 108 weeks in combination with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.	Cemiplimab 350 mg Q3W + Chemotherapy + Ipilimumab 50 mg Q6W Cemiplimab was administered at 350 mg as an IV infusion Q3W for 108 weeks in combination with platinum-based doublet chemotherapy administered IV Q3W for 2 cycles and with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.
Number of Participants With Any Serious TEAEs	2 Participants	2 Participants	—

SECONDARY outcome

Timeframe: Up to 32 months

Population: Safety analysis set (SAF), defined as all enrolled participants who received any amount of study treatment

Outcome measures

Outcome measures
Measure	Pembrolizumab n=3 Participants Due to ceasing enrollment early, no participants were randomized to receive pembrolizumab.	Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W n=2 Participants Cemiplimab was administered at 350 mg as an intravenous (IV) infusion every 3 weeks (Q3W) for 108 weeks in combination with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.	Cemiplimab 350 mg Q3W + Chemotherapy + Ipilimumab 50 mg Q6W Cemiplimab was administered at 350 mg as an IV infusion Q3W for 108 weeks in combination with platinum-based doublet chemotherapy administered IV Q3W for 2 cycles and with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.
Number of Participants With TEAEs Leading to Death	1 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Up to 32 months

Population: Safety analysis set (SAF), defined as all enrolled participants who received any amount of study treatment

Outcome measures

Outcome measures
Measure	Pembrolizumab n=3 Participants Due to ceasing enrollment early, no participants were randomized to receive pembrolizumab.	Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W n=2 Participants Cemiplimab was administered at 350 mg as an intravenous (IV) infusion every 3 weeks (Q3W) for 108 weeks in combination with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.	Cemiplimab 350 mg Q3W + Chemotherapy + Ipilimumab 50 mg Q6W Cemiplimab was administered at 350 mg as an IV infusion Q3W for 108 weeks in combination with platinum-based doublet chemotherapy administered IV Q3W for 2 cycles and with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.
Number of Participants With Laboratory Abnormalities	1 Participants	1 Participants	—

SECONDARY outcome

Timeframe: At 12 months

Population: OS was not assessed due to insufficient data collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At 18 months

Population: OS was not assessed due to insufficient data collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 32 months

Population: Due to the minimal amount of responses and decrease in number of overall participants analyzed for this outcome measure, results are not reported to protect the confidentiality of the participants.

Quality of Life (QoL) as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) four-point scale, with 1 as "not at all" and 4 as "very much." Per protocol, the change in EORTC QLQ-C30 scores from the first assessment to the end of the study were to be summarized descriptively at each post-baseline time point and compared using a mixed effects model, if appropriate.

Outcome measures

Outcome measures
Measure	Pembrolizumab n=2 Participants Due to ceasing enrollment early, no participants were randomized to receive pembrolizumab.	Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W n=2 Participants Cemiplimab was administered at 350 mg as an intravenous (IV) infusion every 3 weeks (Q3W) for 108 weeks in combination with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.	Cemiplimab 350 mg Q3W + Chemotherapy + Ipilimumab 50 mg Q6W Cemiplimab was administered at 350 mg as an IV infusion Q3W for 108 weeks in combination with platinum-based doublet chemotherapy administered IV Q3W for 2 cycles and with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.
Quality of Life (Core 30 Questionnaire)	NA Score on a scale Standard Deviation NA Due to the minimal amount of responses and decrease in number of overall participants analyzed for this outcome measure, results are not reported to protect the confidentiality of the participants.	NA Score on a scale Standard Deviation NA Due to the minimal amount of responses and decrease in number of overall participants analyzed for this outcome measure, results are not reported to protect the confidentiality of the participants.	—

SECONDARY outcome

Timeframe: Up to 32 months

QoL as measured by the Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) to assess lung cancer-associated symptoms and treatment-related side effects among lung cancer patients. The scale for EORTC-QLQ-LC13 is 1-4 for most outcome measures of systems, with 1 rated as "not at all" and 4 rated as "very much." Per protocol, the change in EORTC QLQ-LC13 scores from the first assessment to the end of the study were to be summarized descriptively at each post-baseline time point and compared using a mixed effects model, if appropriate.

Outcome measures

Outcome measures
Measure	Pembrolizumab n=2 Participants Due to ceasing enrollment early, no participants were randomized to receive pembrolizumab.	Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W n=2 Participants Cemiplimab was administered at 350 mg as an intravenous (IV) infusion every 3 weeks (Q3W) for 108 weeks in combination with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.	Cemiplimab 350 mg Q3W + Chemotherapy + Ipilimumab 50 mg Q6W Cemiplimab was administered at 350 mg as an IV infusion Q3W for 108 weeks in combination with platinum-based doublet chemotherapy administered IV Q3W for 2 cycles and with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.
Quality of Life (Lung Cancer 13 Questionnaire)	NA Score on a scale Standard Deviation NA Due to the minimal amount of responses and decrease in number of overall participants analyzed for this outcome measure, results are not reported to protect the confidentiality of the participants.	NA Score on a scale Standard Deviation NA Due to the minimal amount of responses and decrease in number of overall participants analyzed for this outcome measure, results are not reported to protect the confidentiality of the participants.	—

Adverse Events

Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W

Serious events: 2 serious events

Other events: 3 other events

Deaths: 2 deaths

Cemiplimab 350 mg Q3W + Chemotherapy + Ipilimumab 50 mg Q6W

Serious events: 2 serious events

Other events: 2 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W n=3 participants at risk Cemiplimab was administered at 350 mg as an intravenous (IV) infusion every 3 weeks (Q3W) for 108 weeks in combination with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.	Cemiplimab 350 mg Q3W + Chemotherapy + Ipilimumab 50 mg Q6W n=2 participants at risk Cemiplimab was administered at 350 mg as an IV infusion Q3W for 108 weeks in combination with platinum-based doublet chemotherapy administered IV Q3W for 2 cycles and with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.
Cardiac disorders Pericarditis	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Endocrine disorders Secondary adrenocortical insufficiency	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Gastrointestinal disorders Enterocolitis	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Gastrointestinal disorders Gastritis	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
General disorders Multiple organ dysfunction syndrome	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Immune system disorders Cytokine release syndrome	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Musculoskeletal and connective tissue disorders Back pain	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)

Other adverse events

Additional Information

Clinical Trials Administrator

Regeneron Pharmaceuticals, Inc.

Phone: 844-734-6643

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W n=3 participants at risk Cemiplimab was administered at 350 mg as an intravenous (IV) infusion every 3 weeks (Q3W) for 108 weeks in combination with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.	Cemiplimab 350 mg Q3W + Chemotherapy + Ipilimumab 50 mg Q6W n=2 participants at risk Cemiplimab was administered at 350 mg as an IV infusion Q3W for 108 weeks in combination with platinum-based doublet chemotherapy administered IV Q3W for 2 cycles and with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses.
Blood and lymphatic system disorders Anaemia	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	100.0% 2/2 • Number of events 2 • From first dose of study drug to end of study (up to 32 months)
Blood and lymphatic system disorders Leukopenia	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	100.0% 2/2 • Number of events 2 • From first dose of study drug to end of study (up to 32 months)
Blood and lymphatic system disorders Neutropenia	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Endocrine disorders Adrenocortical insufficiency acute	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Endocrine disorders Hypothyroidism	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Endocrine disorders Secondary adrenocortical insufficiency	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Endocrine disorders Hyperthyroidism	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Gastrointestinal disorders Abdominal pain upper	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	100.0% 2/2 • Number of events 4 • From first dose of study drug to end of study (up to 32 months)
Gastrointestinal disorders Nausea	33.3% 1/3 • Number of events 2 • From first dose of study drug to end of study (up to 32 months)	100.0% 2/2 • Number of events 7 • From first dose of study drug to end of study (up to 32 months)
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Gastrointestinal disorders Constipation	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 2 • From first dose of study drug to end of study (up to 32 months)
Gastrointestinal disorders Dyspepsia	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Gastrointestinal disorders Mouth ulceration	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 2 • From first dose of study drug to end of study (up to 32 months)
Gastrointestinal disorders Vomiting	33.3% 1/3 • Number of events 3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 2 • From first dose of study drug to end of study (up to 32 months)
Gastrointestinal disorders Gastritis	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
General disorders Chest pain	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	100.0% 2/2 • Number of events 3 • From first dose of study drug to end of study (up to 32 months)
General disorders Fatigue	66.7% 2/3 • Number of events 4 • From first dose of study drug to end of study (up to 32 months)	100.0% 2/2 • Number of events 2 • From first dose of study drug to end of study (up to 32 months)
General disorders Asthenia	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
General disorders Pain	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
General disorders Influenza like illness	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
General disorders Non-cardiac chest pain	33.3% 1/3 • Number of events 3 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
General disorders Oedema peripheral	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
General disorders Pyrexia	66.7% 2/3 • Number of events 3 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
General disorders Suprapubic pain	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Injury, poisoning and procedural complications Fall	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	100.0% 2/2 • Number of events 2 • From first dose of study drug to end of study (up to 32 months)
Injury, poisoning and procedural complications Thermal burn	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Metabolism and nutrition disorders Decreased appetite	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	100.0% 2/2 • Number of events 5 • From first dose of study drug to end of study (up to 32 months)
Metabolism and nutrition disorders Hypokalaemia	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	100.0% 2/2 • Number of events 3 • From first dose of study drug to end of study (up to 32 months)
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Metabolism and nutrition disorders Hypochloraemia	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Metabolism and nutrition disorders Hypomagnesaemia	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 3 • From first dose of study drug to end of study (up to 32 months)
Metabolism and nutrition disorders Hypoglycaemia	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Metabolism and nutrition disorders Metabolic acidosis	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	100.0% 2/2 • Number of events 4 • From first dose of study drug to end of study (up to 32 months)
Musculoskeletal and connective tissue disorders Arthralgia	66.7% 2/3 • Number of events 2 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Musculoskeletal and connective tissue disorders Back pain	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Nervous system disorders Dizziness	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	100.0% 2/2 • Number of events 3 • From first dose of study drug to end of study (up to 32 months)
Nervous system disorders Balance disorder	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Nervous system disorders Dysgeusia	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 2 • From first dose of study drug to end of study (up to 32 months)
Nervous system disorders Headache	33.3% 1/3 • Number of events 4 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 3 • From first dose of study drug to end of study (up to 32 months)
Nervous system disorders Paraesthesia	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	100.0% 2/2 • Number of events 2 • From first dose of study drug to end of study (up to 32 months)
Skin and subcutaneous tissue disorders Erythema	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 2 • From first dose of study drug to end of study (up to 32 months)
Skin and subcutaneous tissue disorders Hair colour changes	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Skin and subcutaneous tissue disorders Pruritus	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Skin and subcutaneous tissue disorders Rash	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 3 • From first dose of study drug to end of study (up to 32 months)
Skin and subcutaneous tissue disorders Skin reaction	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Vascular disorders Hypertension	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	100.0% 2/2 • Number of events 2 • From first dose of study drug to end of study (up to 32 months)
Vascular disorders Hypotension	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Vascular disorders Aortic arteriosclerosis	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Ear and labyrinth disorders Tinnitus	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Hepatobiliary disorders Immune-mediated hepatitis	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Immune system disorders Drug hypersensitivity	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Infections and infestations Oral candidiasis	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Infections and infestations Fungal oesophagitis	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Infections and infestations Otitis media acute	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Infections and infestations Pneumonia	66.7% 2/3 • Number of events 2 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Infections and infestations Rhinitis	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Infections and infestations Urinary tract infection	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Investigations Liver function test increased	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pseudoprogression	0.00% 0/3 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Respiratory, thoracic and mediastinal disorders Cough	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	50.0% 1/2 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Respiratory, thoracic and mediastinal disorders Haemoptysis	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Respiratory, thoracic and mediastinal disorders Pneumonitis	66.7% 2/3 • Number of events 2 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Cardiac disorders Bradycardia	33.3% 1/3 • Number of events 2 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Cardiac disorders Palpitations	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Eye disorders Vision blurred	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Psychiatric disorders Confusional state	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Psychiatric disorders Insomnia	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Renal and urinary disorders Dysuria	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)
Renal and urinary disorders Oliguria	33.3% 1/3 • Number of events 1 • From first dose of study drug to end of study (up to 32 months)	0.00% 0/2 • From first dose of study drug to end of study (up to 32 months)