Trial Outcomes & Findings for A Study of Pemetrexed and Carboplatin/Cisplatin or Gemcitabine and Carboplatin/Cisplatin With or Without IMC-1121B in Participants Previously Untreated With Recurrent or Advanced Non-Small Cell Lung Cancer (NSCLC) (NCT NCT01160744)

Last Updated: 2019-09-13

Results Overview

PFS was the time from randomization to the first objective progression as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v 1.1) or death from any cause, whichever occurred first. Progressive disease (PD) was defined as ≥20% increase in sum of diameter (SOD) of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 millimeters (mm); appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants alive and without disease progression were censored at the time of the last objective tumor assessment. Participants who did not progress and were lost to follow-up were censored at their last radiographic assessment. If no baseline or post baseline radiologic assessments were available, participants were censored at date of randomization.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

280 participants

Primary outcome timeframe

Randomization to PD or death (up to 24 months)

Results posted on

2019-09-13

Participant Flow

Participants who died (any cause) or had disease progression were considered to be study completers.

Participant milestones

Participant milestones
Measure	Pem + Carb or Cis (Non-Squamous) Pemetrexed (Pem): 500 milligrams/square meter (mg/m²) on Day 1 of every 21-day cycle. Carboplatin (Carb) \[Area Under the Concentration Time Curve 6 (AUC 6)\] : Day 1 of every 21-day cycle. Cisplatin (Cis): 75 mg/m² intravenous (IV) on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Pem + Carb or Cis (Non-Squamous) Ramucirumab (Ram): 10 milligrams/kilogram (mg/kg) Day 1 of every 21-day cycle. Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Gem + Carb or Cis (Squamous) Gemcitabine (Gem): 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb \[Area Under the Concentration Time Curve 5 (AUC 5)\]: Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Gem + Carb or Cis (Squamous) Ram: 10 mg/kg on Day 1 of each every 21-day cycle. Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of each every 21-day cycle. Participants were treated for up to 89 weeks.
Overall Study STARTED	71	69	69	71
Overall Study Received Study Drug	69	67	63	71
Overall Study COMPLETED	60	64	62	67
Overall Study NOT COMPLETED	11	5	7	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Pem + Carb or Cis (Non-Squamous) Pemetrexed (Pem): 500 milligrams/square meter (mg/m²) on Day 1 of every 21-day cycle. Carboplatin (Carb) \[Area Under the Concentration Time Curve 6 (AUC 6)\] : Day 1 of every 21-day cycle. Cisplatin (Cis): 75 mg/m² intravenous (IV) on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Pem + Carb or Cis (Non-Squamous) Ramucirumab (Ram): 10 milligrams/kilogram (mg/kg) Day 1 of every 21-day cycle. Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Gem + Carb or Cis (Squamous) Gemcitabine (Gem): 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb \[Area Under the Concentration Time Curve 5 (AUC 5)\]: Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Gem + Carb or Cis (Squamous) Ram: 10 mg/kg on Day 1 of each every 21-day cycle. Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of each every 21-day cycle. Participants were treated for up to 89 weeks.
Overall Study Withdrawal by Subject	11	5	6	4
Overall Study Not meet inclusion/exclusion criteria	0	0	1	0

Baseline Characteristics

A Study of Pemetrexed and Carboplatin/Cisplatin or Gemcitabine and Carboplatin/Cisplatin With or Without IMC-1121B in Participants Previously Untreated With Recurrent or Advanced Non-Small Cell Lung Cancer (NSCLC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pem + Carb or Cis (Non-Squamous) n=71 Participants Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Pem + Carb or Cis (Non-Squamous) n=69 Participants Ram: 10 mg/kg Day 1 of every 21-day cycle. Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Gem + Carb or Cis (Squamous) n=69 Participants Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Gem + Carb or Cis (Squamous) n=71 Participants Ram: 10 mg/kg on Day 1 of each every 21-day cycle. Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Total n=280 Participants Total of all reporting groups
Age, Customized <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Customized Between 18 and 65 years	37 Participants n=5 Participants	37 Participants n=7 Participants	27 Participants n=5 Participants	34 Participants n=4 Participants	135 Participants n=21 Participants
Age, Customized >=65 years	34 Participants n=5 Participants	32 Participants n=7 Participants	40 Participants n=5 Participants	37 Participants n=4 Participants	143 Participants n=21 Participants
Age, Customized Missing Data	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	33 Participants n=7 Participants	26 Participants n=5 Participants	16 Participants n=4 Participants	101 Participants n=21 Participants
Sex: Female, Male Male	45 Participants n=5 Participants	36 Participants n=7 Participants	43 Participants n=5 Participants	55 Participants n=4 Participants	179 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	6 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	70 Participants n=5 Participants	65 Participants n=7 Participants	68 Participants n=5 Participants	71 Participants n=4 Participants	274 Participants n=21 Participants
Ethnicity (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	0 Participants n=21 Participants
Race/Ethnicity, Customized White	65 Participants n=5 Participants	60 Participants n=7 Participants	65 Participants n=5 Participants	67 Participants n=4 Participants	257 Participants n=21 Participants
Race/Ethnicity, Customized Black	2 Participants n=5 Participants	8 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants	15 Participants n=21 Participants
Race/Ethnicity, Customized Asian	4 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	6 Participants n=21 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Region of Enrollment United States	71 Participants n=5 Participants	69 Participants n=7 Participants	42 Participants n=5 Participants	41 Participants n=4 Participants	223 Participants n=21 Participants
Region of Enrollment Canada	0 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Region of Enrollment Belgium	0 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants	4 Participants n=4 Participants	9 Participants n=21 Participants
Region of Enrollment Poland	0 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	12 Participants n=4 Participants	16 Participants n=21 Participants
Region of Enrollment Germany	0 Participants n=5 Participants	0 Participants n=7 Participants	14 Participants n=5 Participants	8 Participants n=4 Participants	22 Participants n=21 Participants
Region of Enrollment United Kingdom	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	5 Participants n=4 Participants	5 Participants n=21 Participants

PRIMARY outcome

Timeframe: Randomization to PD or death (up to 24 months)

Population: Intent-to-Treat (ITT) Population: All randomized participants. Participants censored: Pem+Carb/Cis=14, Ram+Pem+Carb/Cis=13, Gem+Carb/Cis=14, Ram+Gem+Carb/Cis=18.

Outcome measures

Outcome measures
Measure	Pem + Carb or Cis (Non-Squamous) n=71 Participants Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Pem + Carb or Cis (Non-Squamous) n=69 Participants Ram: 10 mg/kg Day 1 of every 21-day cycle. Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Gem + Carb or Cis (Squamous) n=69 Participants Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Gem + Carb or Cis (Squamous) n=71 Participants Ram: 10 mg/kg on Day 1 of each every 21-day cycle. Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.
Progression-Free Survival (PFS)	5.6 months Interval 4.0 to 5.7	7.2 months Interval 5.8 to 8.4	5.4 months Interval 4.7 to 5.7	5.6 months Interval 4.4 to 6.0

SECONDARY outcome

Timeframe: Day 1, Cycle 1 (3-week cycles) and every 6 weeks thereafter to PD (up to 24 months)

Population: ITT Population: All randomized participants.

Best overall response of CR or PR was defined using RECIST v 1.1 criteria. CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to \<10 mm, and normalization of tumor marker levels of non-target lesions. PR was defined as ≥30% decrease in SOD of target lesions taking as reference the baseline sum diameter. PD was defined as ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR/total number of participants)\*100.

Outcome measures

Outcome measures
Measure	Pem + Carb or Cis (Non-Squamous) n=71 Participants Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Pem + Carb or Cis (Non-Squamous) n=69 Participants Ram: 10 mg/kg Day 1 of every 21-day cycle. Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Gem + Carb or Cis (Squamous) n=69 Participants Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Gem + Carb or Cis (Squamous) n=71 Participants Ram: 10 mg/kg on Day 1 of each every 21-day cycle. Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.
Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]	38.0 percentage of participants	49.3 percentage of participants	24.6 percentage of participants	46.5 percentage of participants

SECONDARY outcome

Timeframe: Randomization to the date of death from any cause (up to 31.3 months)

Population: ITT Population: All randomized participants. Participants censored: Pem+Carb/Cis=22, Ram+Pem+Carb/Cis=16, Gem+Carb/Cis=32, Ram+Gem+Carb/Cis=32. Censored participants were included in the analysis.

OS was defined as the time from the date of randomization to the date of death from any cause. If the participant was alive at the end of the follow-up period or was lost to follow-up, OS was censored on the last date the participant was known to be alive.

Outcome measures

Outcome measures
Measure	Pem + Carb or Cis (Non-Squamous) n=71 Participants Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Pem + Carb or Cis (Non-Squamous) n=69 Participants Ram: 10 mg/kg Day 1 of every 21-day cycle. Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Gem + Carb or Cis (Squamous) n=69 Participants Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Gem + Carb or Cis (Squamous) n=71 Participants Ram: 10 mg/kg on Day 1 of each every 21-day cycle. Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.
Overall Survival (OS)	10.4 months Interval 8.2 to 15.9	13.9 months Interval 10.0 to 17.8	11.3 months Interval 9.7 to 13.3	10.4 months Interval 7.8 to 14.8

SECONDARY outcome

Timeframe: Time of first response (CR or PR) until PD or death (up to 24 months)

Population: All randomized participants with a best overall response of CR or PR. Participants censored: Pem+Carb/Cis=44, Ram+Pem+Carb/Cis=35, Gem+Carb/Cis=50, Ram+Gem+Carb/Cis=37.

DOR was measured from the time criteria were met for the first objectively recorded CR or PR until the first date criteria for PD were met or death. Response was defined using RECIST v 1.1 criteria. CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to \<10 mm, and normalization of tumor marker level of non-target lesions. PR was defined as ≥30% decrease SOD of target lesions taking as reference the baseline sum diameter. PD was defined as ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants who did not relapse were censored at the day of their last objective tumor assessment.

Outcome measures

Outcome measures
Measure	Pem + Carb or Cis (Non-Squamous) n=27 Participants Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Pem + Carb or Cis (Non-Squamous) n=34 Participants Ram: 10 mg/kg Day 1 of every 21-day cycle. Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Gem + Carb or Cis (Squamous) n=17 Participants Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Gem + Carb or Cis (Squamous) n=33 Participants Ram: 10 mg/kg on Day 1 of each every 21-day cycle. Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.
Duration of Response (DOR)	4.5 months Interval 3.1 to 5.7	5.5 months Interval 4.4 to 5.8	4.3 months Interval 4.2 to 5.5	4.3 months Interval 3.3 to 5.6

SECONDARY outcome

Timeframe: Day 1, Cycle 1 (3-week cycles) Up to 3 Years

Population: All randomized participants who received at least 1 dose of study drug.

Data presented are the number of participants with at least 1 treatment-emergent adverse event (TEAE) and treatment-emergent serious adverse event (SAE), as well as, the number of participants who died during the study. TEAEs were defined as serious and other non-serious AEs that occurred or worsened after study treatment (regardless of causality). A summary of SAEs and other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.

Outcome measures

Outcome measures
Measure	Pem + Carb or Cis (Non-Squamous) n=69 Participants Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Pem + Carb or Cis (Non-Squamous) n=67 Participants Ram: 10 mg/kg Day 1 of every 21-day cycle. Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Gem + Carb or Cis (Squamous) n=63 Participants Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Gem + Carb or Cis (Squamous) n=71 Participants Ram: 10 mg/kg on Day 1 of each every 21-day cycle. Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Who Died Treatment-Emergent SAE	38 Participants	44 Participants	29 Participants	39 Participants
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Who Died Treatment-Emergent Adverse Event	68 Participants	67 Participants	63 Participants	71 Participants
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Who Died Deaths	51 Participants	55 Participants	55 Participants	56 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1, Cycle 1 (3-week cycles) and every 6 weeks thereafter to PD (up to 24 months)

Population: ITT Population: All randomized participants.

DCR: percentage of participants with CR, PR, or SD using RECIST v 1.1 criteria. CR: disappearance of all lesions, pathological lymph node reduction in short axis to \<10 mm, and normalization of tumor marker levels of non-target lesions. PR: ≥30% decrease in SOD of target lesions taking as reference baseline sum diameter. PD: ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference smallest sum of longest diameters recorded since treatment started and an absolute increase in sum diameter ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. SD: neither sufficient shrinkage to qualify for PR nor increase to qualify for PD. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR+SD/total number of participants)\*100.

Outcome measures

Outcome measures
Measure	Pem + Carb or Cis (Non-Squamous) n=71 Participants Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Pem + Carb or Cis (Non-Squamous) n=69 Participants Ram: 10 mg/kg Day 1 of every 21-day cycle. Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Gem + Carb or Cis (Squamous) n=69 Participants Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Gem + Carb or Cis (Squamous) n=71 Participants Ram: 10 mg/kg on Day 1 of each every 21-day cycle. Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.
Percentage of Participants With CR, PR, or Stable Disease (SD) [Disease Control Rate (DCR)]	70.4 percentage of participants Interval 61.5 to 79.3	85.5 percentage of participants Interval 78.5 to 92.5	66.7 percentage of participants Interval 57.3 to 76.0	73.2 percentage of participants Interval 64.6 to 81.9

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6 weeks

Population: All randomized participants with results at baseline and 6 weeks.

CTS was defined as the log ratio of tumor size at 6 weeks to tumor size at baseline. CTS at 6 weeks=Log (Sum of Target Lesion Measurements at 6 Weeks)-Log (Sum of Target Lesion Measurements at Baseline).

Outcome measures

Outcome measures
Measure	Pem + Carb or Cis (Non-Squamous) n=53 Participants Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Pem + Carb or Cis (Non-Squamous) n=58 Participants Ram: 10 mg/kg Day 1 of every 21-day cycle. Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Gem + Carb or Cis (Squamous) n=50 Participants Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Gem + Carb or Cis (Squamous) n=53 Participants Ram: 10 mg/kg on Day 1 of each every 21-day cycle. Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.
Change in Tumor Size (CTS)	-0.2 log ratio Standard Deviation 0.23	-0.2 log ratio Standard Deviation 0.22	-0.3 log ratio Standard Deviation 0.31	-0.4 log ratio Standard Deviation 0.39

Adverse Events

Pem + Carb or Cis (Non-Squamous)

Serious events: 38 serious events

Other events: 67 other events

Deaths: 51 deaths

Ram + Pem + Carb or Cis (Non-Squamous)

Serious events: 44 serious events

Other events: 66 other events

Deaths: 55 deaths

Gem + Carb or Cis (Squamous)

Serious events: 29 serious events

Other events: 62 other events

Deaths: 55 deaths

Ram + Gem + Carb or Cis (Squamous)

Serious events: 39 serious events

Other events: 71 other events

Deaths: 56 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study publication or if the draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. The sponsor may request publication delay up to 90 days to seek patent protection.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Pem + Carb or Cis (Non-Squamous) n=69 participants at risk Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Pem + Carb or Cis (Non-Squamous) n=67 participants at risk Ram: 10 mg/kg Day 1 of every 21-day cycle. Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Gem + Carb or Cis (Squamous) n=63 participants at risk Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Gem + Carb or Cis (Squamous) n=71 participants at risk Ram: 10 mg/kg on Day 1 of each every 21-day cycle. Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.
Investigations Oxygen saturation decreased	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.5% 1/67 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Investigations Platelet count decreased	1.4% 1/69 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/67 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.5% 1/67 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Blood and lymphatic system disorders Anaemia	1.4% 1/69 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.5% 1/67 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	3.2% 2/63 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	7.0% 5/71 • Number of events 5 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Blood and lymphatic system disorders Febrile neutropenia	1.4% 1/69 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	3.0% 2/67 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	2.8% 2/71 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Blood and lymphatic system disorders Leukopenia	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/67 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Blood and lymphatic system disorders Neutropenia	1.4% 1/69 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	3.0% 2/67 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	5.6% 4/71 • Number of events 4 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.5% 1/67 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.6% 1/63 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Blood and lymphatic system disorders Thrombocytopenia	2.9% 2/69 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	6.0% 4/67 • Number of events 5 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	3.2% 2/63 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	11.3% 8/71 • Number of events 10 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Cardiac disorders Acute coronary syndrome	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/67 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Cardiac disorders Acute myocardial infarction	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.5% 1/67 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Cardiac disorders Angina pectoris	1.4% 1/69 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.5% 1/67 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Cardiac disorders Atrial fibrillation	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	3.0% 2/67 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	3.2% 2/63 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Cardiac disorders Bradycardia	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/67 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.6% 1/63 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Cardiac disorders Bundle branch block left	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/67 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Cardiac disorders Cardiac arrest	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/67 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Cardiac disorders Cardiac failure congestive	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.5% 1/67 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.6% 1/63 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Cardiac disorders Cardio-respiratory arrest	1.4% 1/69 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/67 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.6% 1/63 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Cardiac disorders Cardiovascular disorder	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.5% 1/67 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Cardiac disorders Coronary artery occlusion	1.4% 1/69 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/67 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Cardiac disorders Left ventricular dysfunction	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/67 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Cardiac disorders Myocardial infarction	1.4% 1/69 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	3.0% 2/67 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	3.2% 2/63 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Cardiac disorders Supraventricular tachycardia	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.5% 1/67 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Cardiac disorders Tachycardia	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/67 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Endocrine disorders Inappropriate antidiuretic hormone secretion	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/67 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Eye disorders Vision blurred	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/67 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.6% 1/63 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Abdominal pain	2.9% 2/69 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/67 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.5% 1/67 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Colitis ischaemic	1.4% 1/69 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/67 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Constipation	1.4% 1/69 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.5% 1/67 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Diarrhoea	2.9% 2/69 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/67 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Duodenal ulcer	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/67 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.6% 1/63 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Gastritis	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.5% 1/67 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.5% 1/67 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Intestinal ischaemia	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.5% 1/67 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Intestinal perforation	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.5% 1/67 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Lip haemorrhage	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/67 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Nausea	5.8% 4/69 • Number of events 4 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	7.5% 5/67 • Number of events 5 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	3.2% 2/63 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Pancreatitis	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.5% 1/67 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Vomiting	5.8% 4/69 • Number of events 4 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	7.5% 5/67 • Number of events 6 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.6% 1/63 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.

Other adverse events
Measure	Pem + Carb or Cis (Non-Squamous) n=69 participants at risk Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Pem + Carb or Cis (Non-Squamous) n=67 participants at risk Ram: 10 mg/kg Day 1 of every 21-day cycle. Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Gem + Carb or Cis (Squamous) n=63 participants at risk Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.	Ram + Gem + Carb or Cis (Squamous) n=71 participants at risk Ram: 10 mg/kg on Day 1 of each every 21-day cycle. Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks.
Nervous system disorders Headache	11.6% 8/69 • Number of events 12 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	28.4% 19/67 • Number of events 33 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	7.9% 5/63 • Number of events 6 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	19.7% 14/71 • Number of events 20 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Nervous system disorders Hypoaesthesia	5.8% 4/69 • Number of events 8 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	4.5% 3/67 • Number of events 6 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.6% 1/63 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	4.2% 3/71 • Number of events 3 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Muscle spasms	1.4% 1/69 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	7.5% 5/67 • Number of events 5 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	3.2% 2/63 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	5.6% 4/71 • Number of events 4 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	5.8% 4/69 • Number of events 6 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	11.9% 8/67 • Number of events 10 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	6.3% 4/63 • Number of events 5 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	7.0% 5/71 • Number of events 5 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	2.9% 2/69 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	10.4% 7/67 • Number of events 11 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	4.8% 3/63 • Number of events 3 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	5.6% 4/71 • Number of events 5 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Myalgia	4.3% 3/69 • Number of events 4 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	9.0% 6/67 • Number of events 6 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.6% 1/63 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	4.2% 3/71 • Number of events 5 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Nervous system disorders Dysgeusia	8.7% 6/69 • Number of events 10 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	17.9% 12/67 • Number of events 16 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	12.7% 8/63 • Number of events 10 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	9.9% 7/71 • Number of events 7 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Pain in extremity	5.8% 4/69 • Number of events 4 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	11.9% 8/67 • Number of events 9 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.6% 1/63 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	2.8% 2/71 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Nervous system disorders Dizziness	18.8% 13/69 • Number of events 18 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	11.9% 8/67 • Number of events 8 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	9.5% 6/63 • Number of events 7 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	5.6% 4/71 • Number of events 4 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Blood and lymphatic system disorders Anaemia	53.6% 37/69 • Number of events 103 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	47.8% 32/67 • Number of events 95 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	63.5% 40/63 • Number of events 94 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	53.5% 38/71 • Number of events 111 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Blood and lymphatic system disorders Leukopenia	5.8% 4/69 • Number of events 14 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	11.9% 8/67 • Number of events 20 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	15.9% 10/63 • Number of events 23 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	14.1% 10/71 • Number of events 36 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Blood and lymphatic system disorders Neutropenia	24.6% 17/69 • Number of events 42 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	32.8% 22/67 • Number of events 70 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	55.6% 35/63 • Number of events 94 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	73.2% 52/71 • Number of events 152 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Blood and lymphatic system disorders Thrombocytopenia	21.7% 15/69 • Number of events 48 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	32.8% 22/67 • Number of events 72 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	42.9% 27/63 • Number of events 73 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	50.7% 36/71 • Number of events 128 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Cardiac disorders Atrial fibrillation	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.5% 1/67 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	6.3% 4/63 • Number of events 4 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Cardiac disorders Tachycardia	5.8% 4/69 • Number of events 4 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	3.0% 2/67 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	6.3% 4/63 • Number of events 4 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	4.2% 3/71 • Number of events 3 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Ear and labyrinth disorders Tinnitus	2.9% 2/69 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	7.5% 5/67 • Number of events 7 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	4.8% 3/63 • Number of events 3 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Eye disorders Lacrimation increased	14.5% 10/69 • Number of events 10 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	11.9% 8/67 • Number of events 10 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	3.2% 2/63 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Abdominal distension	8.7% 6/69 • Number of events 8 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	6.0% 4/67 • Number of events 6 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/63 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Abdominal pain	10.1% 7/69 • Number of events 9 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	17.9% 12/67 • Number of events 17 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	4.8% 3/63 • Number of events 4 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	2.8% 2/71 • Number of events 3 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	4.5% 3/67 • Number of events 4 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	7.9% 5/63 • Number of events 6 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	5.6% 4/71 • Number of events 5 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Constipation	30.4% 21/69 • Number of events 29 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	28.4% 19/67 • Number of events 27 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	33.3% 21/63 • Number of events 28 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	25.4% 18/71 • Number of events 29 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Diarrhoea	27.5% 19/69 • Number of events 28 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	28.4% 19/67 • Number of events 23 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	19.0% 12/63 • Number of events 14 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	12.7% 9/71 • Number of events 12 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Dry mouth	2.9% 2/69 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	6.0% 4/67 • Number of events 4 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	3.2% 2/63 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Dyspepsia	7.2% 5/69 • Number of events 6 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	9.0% 6/67 • Number of events 8 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	4.8% 3/63 • Number of events 3 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Dysphagia	2.9% 2/69 • Number of events 3 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	7.5% 5/67 • Number of events 7 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	6.3% 4/63 • Number of events 4 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Gastrooesophageal reflux disease	4.3% 3/69 • Number of events 3 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	6.0% 4/67 • Number of events 4 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.6% 1/63 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	5.6% 4/71 • Number of events 4 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Gingival bleeding	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	6.0% 4/67 • Number of events 6 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.6% 1/63 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	2.8% 2/71 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Nausea	56.5% 39/69 • Number of events 71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	52.2% 35/67 • Number of events 65 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	57.1% 36/63 • Number of events 51 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	38.0% 27/71 • Number of events 44 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Stomatitis	8.7% 6/69 • Number of events 6 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	13.4% 9/67 • Number of events 13 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	9.5% 6/63 • Number of events 9 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	4.2% 3/71 • Number of events 3 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Vomiting	34.8% 24/69 • Number of events 34 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	32.8% 22/67 • Number of events 35 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	19.0% 12/63 • Number of events 15 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	25.4% 18/71 • Number of events 23 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
General disorders Asthenia	2.9% 2/69 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	11.9% 8/67 • Number of events 12 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	11.1% 7/63 • Number of events 10 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	7.0% 5/71 • Number of events 8 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
General disorders Chills	7.2% 5/69 • Number of events 5 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.5% 1/67 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	3.2% 2/63 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	7.0% 5/71 • Number of events 6 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
General disorders Fatigue	62.3% 43/69 • Number of events 85 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	65.7% 44/67 • Number of events 97 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	54.0% 34/63 • Number of events 62 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	54.9% 39/71 • Number of events 79 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
General disorders Infusion site pain	0.00% 0/69 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.5% 1/67 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	6.3% 4/63 • Number of events 4 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
General disorders Mucosal inflammation	8.7% 6/69 • Number of events 11 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	11.9% 8/67 • Number of events 14 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	7.9% 5/63 • Number of events 5 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	4.2% 3/71 • Number of events 3 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
General disorders Non-cardiac chest pain	4.3% 3/69 • Number of events 3 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	6.0% 4/67 • Number of events 11 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	6.3% 4/63 • Number of events 4 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	5.6% 4/71 • Number of events 4 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
General disorders Oedema peripheral	23.2% 16/69 • Number of events 19 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	25.4% 17/67 • Number of events 23 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	15.9% 10/63 • Number of events 12 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	19.7% 14/71 • Number of events 23 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
General disorders Pyrexia	17.4% 12/69 • Number of events 19 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	11.9% 8/67 • Number of events 9 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	9.5% 6/63 • Number of events 7 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	8.5% 6/71 • Number of events 8 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Infections and infestations Nasopharyngitis	5.8% 4/69 • Number of events 8 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	3.0% 2/67 • Number of events 3 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	4.8% 3/63 • Number of events 4 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/71 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Infections and infestations Pneumonia	5.8% 4/69 • Number of events 4 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	3.0% 2/67 • Number of events 2 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	9.5% 6/63 • Number of events 6 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	4.2% 3/71 • Number of events 4 • Baseline through Study Completion (Up To 3 Years). All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.