Trial Outcomes & Findings for Study of Bevacizumab + mFOLFOX6 Versus Bevacizumab + FOLFIRI With Biomarker Stratification in Participants With Previously Untreated Metastatic Colorectal Cancer (mCRC) (NCT NCT01374425)

NCT ID: NCT01374425

Last Updated: 2016-08-11

Results Overview

Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as greater than or equal to (≥) 20 percent (%) increase in sum of largest diameters (LD) of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 millimeters (mm). Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% confidence interval (CI) was computed using the method of Brookmeyer and Crowley.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 376 participants
• Primary outcome timeframe: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
• Results posted on: 2016-08-11

Participant Flow

The trial included a 21-day Screening period during which participants provided information for demographics, medical history, and cancer/treatment history and completed urinalysis collection.

Participant milestones

Measure	Bevacizumab + mFOLFOX6 Participants with untreated metastatic colorectal cancer (mCRC) who were candidates for first-line therapy received bevacizumab plus leucovorin, 5-fluorouracil, and oxaliplatin (mFOLFOX6) until disease progression or unacceptable toxicity. Bevacizumab was given as 5 milligrams per kilogram (mg/kg), leucovorin as 400 milligrams per meter-squared (mg/m\^2), oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via intravenous (IV) infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus leucovorin, 5-fluorouracil, and irinotecan (FOLFIRI) until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Overall Study STARTED	188	188
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	188	188

Reasons for withdrawal

Measure	Bevacizumab + mFOLFOX6 Participants with untreated metastatic colorectal cancer (mCRC) who were candidates for first-line therapy received bevacizumab plus leucovorin, 5-fluorouracil, and oxaliplatin (mFOLFOX6) until disease progression or unacceptable toxicity. Bevacizumab was given as 5 milligrams per kilogram (mg/kg), leucovorin as 400 milligrams per meter-squared (mg/m\^2), oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via intravenous (IV) infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus leucovorin, 5-fluorouracil, and irinotecan (FOLFIRI) until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Overall Study Radiographic Disease Progression	86	81
Overall Study Clinical Disease Progression	9	6
Overall Study Adverse Event	29	18
Overall Study Death (Progression of Disease)	1	0
Overall Study Death (Adverse Event)	2	4
Overall Study Withdrawal by Subject	6	7
Overall Study Refused Treatment	10	24
Overall Study Protocol Violation	2	3
Overall Study Sponsor Decision	0	1
Overall Study Lost to Follow-up	2	1
Overall Study Other	41	43

Baseline Characteristics

Study of Bevacizumab + mFOLFOX6 Versus Bevacizumab + FOLFIRI With Biomarker Stratification in Participants With Previously Untreated Metastatic Colorectal Cancer (mCRC)

Baseline characteristics by cohort

Measure	Bevacizumab + mFOLFOX6 n=188 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=188 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Total n=376 Participants Total of all reporting groups
Age, Continuous	59.2 years STANDARD_DEVIATION 10.88 • n=5 Participants	60.7 years STANDARD_DEVIATION 10.66 • n=7 Participants	59.9 years STANDARD_DEVIATION 10.78 • n=5 Participants
Sex: Female, Male Female	66 Participants n=5 Participants	71 Participants n=7 Participants	137 Participants n=5 Participants
Sex: Female, Male Male	122 Participants n=5 Participants	117 Participants n=7 Participants	239 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)

Population: Intent-to-treat (ITT) Population

Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as greater than or equal to (≥) 20 percent (%) increase in sum of largest diameters (LD) of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 millimeters (mm). Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% confidence interval (CI) was computed using the method of Brookmeyer and Crowley.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=188 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=188 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	10.09 months Interval 8.8 to 11.56	12.55 months Interval 10.48 to 14.29

PRIMARY outcome

Timeframe: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm. Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=64 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=67 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
PFS According to RECIST Version 1.1 in Participants With High ERCC-1 Levels	9.92 months Interval 8.51 to 12.48	11.17 months Interval 9.1 to 17.84

PRIMARY outcome

Timeframe: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm. Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=124 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=120 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
PFS According to RECIST Version 1.1 in Participants With Low ERCC-1 Levels	10.97 months Interval 8.54 to 12.29	12.68 months Interval 10.48 to 14.49

PRIMARY outcome

Timeframe: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm. Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=131 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=244 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
PFS According to RECIST Version 1.1 in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels	10.87 months Interval 9.1 to 12.68	11.56 months Interval 9.95 to 12.98

PRIMARY outcome

Timeframe: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm. Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=185 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=185 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
PFS According to RECIST Version 1.1 in Participants With High Vascular Endothelial Growth Factor (VEGF)-A Levels Versus Participants With Low VEGF-A Levels	10.02 months Interval 8.8 to 11.17	12.68 months Interval 10.9 to 14.26

SECONDARY outcome

Timeframe: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm. Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=28 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=31 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
PFS According to RECIST Version 1.1 in Participants With High ERCC-1 and High VEGF-A Levels	8.80 months Interval 5.91 to 10.02	11.17 months Interval 8.11 to 18.07

SECONDARY outcome

Timeframe: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm. Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=35 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=35 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
PFS According to RECIST Version 1.1 in Participants With High ERCC-1 and Low VEGF-A Levels	12.52 months Interval 9.43 to 15.64	12.68 months Interval 8.18 to 20.83

SECONDARY outcome

Timeframe: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm. Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=66 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=59 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
PFS According to RECIST Version 1.1 in Participants With Low ERCC-1 and High VEGF-A Levels	9.76 months Interval 8.18 to 12.45	11.07 months Interval 8.18 to 14.29

SECONDARY outcome

Timeframe: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm. Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=55 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=60 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
PFS According to RECIST Version 1.1 in Participants With Low ERCC-1 and Low VEGF-A Levels	11.10 months Interval 8.54 to 13.08	14.32 months Interval 11.56 to 14.98

SECONDARY outcome

Timeframe: From Baseline until death (maximum up to 45 months overall)

Population: ITT Population

Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. OS was defined as the time from randomization to death. The median duration of OS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=188 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=188 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Overall Survival (OS)	23.85 months Interval 20.4 to 26.05	27.47 months Interval 24.64 to 36.73

SECONDARY outcome

Timeframe: From Baseline until death (maximum up to 45 months overall)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. OS was defined as the time from randomization to death. The median duration of OS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=64 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=67 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
OS in Participants With High ERCC-1 Levels	22.54 months Interval 17.02 to 26.05	26.51 months Interval 19.09 to 36.73

SECONDARY outcome

Timeframe: From Baseline until death (maximum up to 45 months overall)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. OS was defined as the time from randomization to death. The median duration of OS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=124 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=120 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
OS in Participants With Low ERCC-1 Levels	25.53 months Interval 20.4 to 28.75	27.93 months Interval 24.97 to 38.44

SECONDARY outcome

Timeframe: From Baseline until death (maximum up to 45 months overall)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. OS was defined as the time from randomization to death. The median duration of OS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=131 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=244 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
OS in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels	23.23 months Interval 19.09 to 26.94	27.27 months Interval 24.34 to 31.28

SECONDARY outcome

Timeframe: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)

Population: ITT Population

Objective response was defined as complete response (CR) or partial response (PR) according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to less than (<) 10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. The percentage of participants with CR or PR was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=188 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=188 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Percentage of Participants With Objective Response According to RECIST Version 1.1	61.2 percentage of participants Interval 54.2 to 68.1	65.4 percentage of participants Interval 58.6 to 72.2

SECONDARY outcome

Timeframe: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Objective response was defined as CR or PR according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. The percentage of participants with CR or PR was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=64 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=67 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With High ERCC-1 Levels	56.3 percentage of participants Interval 44.1 to 68.4	65.7 percentage of participants Interval 54.3 to 77.0

SECONDARY outcome

Timeframe: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Objective response was defined as CR or PR according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. The percentage of participants with CR or PR was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=124 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=120 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With Low ERCC-1 Levels	63.7 percentage of participants Interval 55.2 to 72.2	65.8 percentage of participants Interval 57.3 to 74.3

SECONDARY outcome

Timeframe: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Objective response was defined as CR or PR according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. The percentage of participants with CR or PR was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=131 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=244 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels	61.1 percentage of participants Interval 52.7 to 69.4	64.8 percentage of participants Interval 58.8 to 70.7

SECONDARY outcome

Timeframe: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)

Population: ITT Population

Disease control was defined as CR, PR, or stable disease (SD) according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for disease progression (≥20% increase in sum of LD of target lesions plus absolute increase ≥5 mm) in reference to the smallest sum of LD on study. The percentage of participants with CR, PR, or SD was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=188 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=188 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Percentage of Participants With Disease Control According to RECIST Version 1.1	93.1 percentage of participants Interval 89.5 to 96.7	91.0 percentage of participants Interval 86.9 to 95.1

SECONDARY outcome

Timeframe: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Disease control was defined as CR, PR, or SD according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for disease progression (≥20% increase in sum of LD of target lesions plus absolute increase ≥5 mm) in reference to the smallest sum of LD on study. The percentage of participants with CR, PR, or SD was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=64 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=67 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Percentage of Participants With Disease Control According to RECIST Version 1.1 in Participants With High ERCC-1 Levels	93.8 percentage of participants Interval 87.8 to 99.7	85.1 percentage of participants Interval 76.5 to 93.6

SECONDARY outcome

Timeframe: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Disease control was defined as CR, PR, or SD according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for disease progression (≥20% increase in sum of LD of target lesions plus absolute increase ≥5 mm) in reference to the smallest sum of LD on study. The percentage of participants with CR, PR, or SD was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=124 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=120 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Percentage of Participants With Disease Control According to RECIST Version 1.1 in Participants With Low ERCC-1 Levels	92.7 percentage of participants Interval 88.2 to 97.3	95.0 percentage of participants Interval 91.1 to 98.9

SECONDARY outcome

Timeframe: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Disease control was defined as CR, PR, or SD according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for disease progression (≥20% increase in sum of LD of target lesions plus absolute increase ≥5 mm) in reference to the smallest sum of LD on study. The percentage of participants with CR, PR, or SD was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=131 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=244 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Percentage of Participants With Disease Control According to RECIST Version 1.1 in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels	89.3 percentage of participants Interval 84.0 to 94.6	93.9 percentage of participants Interval 90.8 to 96.9

SECONDARY outcome

Timeframe: At time of resective surgery during study (maximum up to 45 months overall)

Population: ITT Population; only those participants with liver or liver plus lymph node metastases were included in the analysis.

The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. R1 was defined as the presence of exposed tumor or histologically detected tumor cells at the line of transection, or <1 mm microscopic margins. In the case of use of radiofrequency ablation or cryotherapy, the resection was considered as R1. R2 was defined as macroscopic positive margins or incomplete resection at time of surgery. The percentage of participants with resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=67 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=55 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Percentage of Participants With Liver Metastasis Resection	14.9 percentage of participants Interval 6.4 to 23.5	10.9 percentage of participants Interval 2.7 to 19.1

SECONDARY outcome

Timeframe: At time of resective surgery during study (maximum up to 45 months overall)

Population: ITT Population; only those participants with liver or liver plus lymph node metastases were included in the analysis.

The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. The percentage of participants with R0 resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=67 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=55 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Percentage of Participants With Complete Liver Metastasis Resection	11.9 percentage of participants Interval 4.2 to 19.7	5.5 percentage of participants Interval 0.0 to 11.5

SECONDARY outcome

Timeframe: At time of resective surgery during study (maximum up to 45 months overall)

Population: ITT Population; only those participants with liver or liver plus lymph node metastases were included in the analysis. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. R1 was defined as the presence of exposed tumor or histologically detected tumor cells at the line of transection, or <1 mm microscopic margins. In the case of use of radiofrequency ablation or cryotherapy, the resection was considered as R1. R2 was defined as macroscopic positive margins or incomplete resection at time of surgery. The percentage of participants with resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=17 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=15 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Percentage of Participants With Liver Metastasis Resection in Participants With High ERCC-1 Levels	17.6 percentage of participants Interval 0.0 to 35.8	6.7 percentage of participants Interval 0.0 to 19.3

SECONDARY outcome

Timeframe: At time of resective surgery during study (maximum up to 45 months overall)

Population: ITT Population; only those participants with liver or liver plus lymph node metastases were included in the analysis. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. The percentage of participants with R0 resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=17 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=15 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Percentage of Participants With Complete Liver Metastasis Resection in Participants With High ERCC-1 Levels	17.6 percentage of participants Interval 0.0 to 35.8	6.7 percentage of participants Interval 0.0 to 19.3

SECONDARY outcome

Timeframe: At time of resective surgery during study (maximum up to 45 months overall)

Population: ITT Population; only those participants with liver or liver plus lymph node metastases were included in the analysis. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. R1 was defined as the presence of exposed tumor or histologically detected tumor cells at the line of transection, or <1 mm microscopic margins. In the case of use of radiofrequency ablation or cryotherapy, the resection was considered as R1. R2 was defined as macroscopic positive margins or incomplete resection at time of surgery. The percentage of participants with resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=124 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=120 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Percentage of Participants With Liver Metastasis Resection in Participants With Low ERCC-1 Levels	10.5 percentage of participants Interval 5.1 to 15.9	7.5 percentage of participants Interval 2.8 to 12.2

SECONDARY outcome

Timeframe: At time of resective surgery during study (maximum up to 45 months overall)

Population: ITT Population; only those participants with liver or liver plus lymph node metastases were included in the analysis. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. The percentage of participants with R0 resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=124 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=120 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Percentage of Participants With Complete Liver Metastasis Resection in Participants With Low ERCC-1 Levels	8.9 percentage of participants Interval 3.9 to 13.9	3.3 percentage of participants Interval 0.1 to 6.5

SECONDARY outcome

Timeframe: At time of resective surgery during study (maximum up to 45 months overall)

Population: ITT Population; only those participants with liver or liver plus lymph node metastases were included in the analysis. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. R1 was defined as the presence of exposed tumor or histologically detected tumor cells at the line of transection, or <1 mm microscopic margins. In the case of use of radiofrequency ablation or cryotherapy, the resection was considered as R1. R2 was defined as macroscopic positive margins or incomplete resection at time of surgery. The percentage of participants with resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=131 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=244 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Percentage of Participants With Liver Metastasis Resection in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels	4.6 percentage of participants Interval 1.0 to 8.2	9.0 percentage of participants Interval 5.4 to 12.6

SECONDARY outcome

Timeframe: At time of resective surgery during study (maximum up to 45 months overall)

Population: ITT Population; only those participants with liver or liver plus lymph node metastases were included in the analysis. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. The percentage of participants with R0 resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=131 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=244 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Percentage of Participants With Complete Liver Metastasis Resection in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels	4.6 percentage of participants Interval 1.0 to 8.2	6.1 percentage of participants Interval 3.1 to 9.2

SECONDARY outcome

Timeframe: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm. Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=208 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=128 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
PFS According to RECIST Version 1.1 in Participants With Wild-Type V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Versus Participants With Mutant KRAS	12.45 months Interval 10.48 to 14.06	10.94 months Interval 8.77 to 12.35

SECONDARY outcome

Timeframe: From Baseline until death (maximum up to 45 months overall)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. OS was defined as the time from randomization to death. The median duration of OS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=185 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=185 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
OS in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels	22.83 months Interval 18.76 to 27.27	27.93 months Interval 24.97 to 36.01

SECONDARY outcome

Timeframe: From Baseline until death (maximum up to 45 months overall)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. OS was defined as the time from randomization to death. The median duration of OS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=208 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=128 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
OS in Participants With Wild-Type KRAS Versus Participants With Mutant KRAS	28.75 months Interval 24.77 to 36.73	24.64 months Interval 19.98 to 26.94

SECONDARY outcome

Timeframe: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Objective response was defined as CR or PR according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. The percentage of participants with CR or PR was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=185 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=185 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels	60.5 percentage of participants Interval 53.5 to 67.6	66.5 percentage of participants Interval 59.7 to 73.3

SECONDARY outcome

Timeframe: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Objective response was defined as CR or PR according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. The percentage of participants with CR or PR was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=208 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=128 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With Wild-Type KRAS Versus Participants With Mutant KRAS	66.3 percentage of participants Interval 59.9 to 72.8	60.9 percentage of participants Interval 52.5 to 69.4

SECONDARY outcome

Timeframe: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)

Population: ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Disease control was defined as CR, PR, or SD according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for disease progression (≥20% increase in sum of LD of target lesions plus absolute increase ≥5 mm) in reference to the smallest sum of LD on study. The percentage of participants with CR, PR, or SD was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=185 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=185 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Percentage of Participants With Disease Control According to RECIST Version 1.1 in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels	91.9 percentage of participants Interval 88.0 to 95.8	93.0 percentage of participants Interval 89.3 to 96.7

SECONDARY outcome

Timeframe: At time of resective surgery during study (maximum up to 45 months overall)

Population: ITT Population; only those participants with liver or liver plus lymph node metastases were included in the analysis. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. R1 was defined as the presence of exposed tumor or histologically detected tumor cells at the line of transection, or <1 mm microscopic margins. In the case of use of radiofrequency ablation or cryotherapy, the resection was considered as R1. R2 was defined as macroscopic positive margins or incomplete resection at time of surgery. The percentage of participants with resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=185 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=185 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Percentage of Participants With Liver Metastasis Resection in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels	5.9 percentage of participants Interval 2.5 to 9.4	9.2 percentage of participants Interval 5.0 to 13.4

SECONDARY outcome

Timeframe: At time of resective surgery during study (maximum up to 45 months overall)

Population: ITT Population; only those participants with liver or liver plus lymph node metastases were included in the analysis. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. The percentage of participants with R0 resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Outcome measures

Measure	Bevacizumab + mFOLFOX6 n=185 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=185 Participants Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Percentage of Participants With Complete Liver Metastasis Resection in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels	3.2 percentage of participants Interval 0.7 to 5.8	8.1 percentage of participants Interval 4.2 to 12.0

Adverse Events

Bevacizumab + mFOLFOX6

Serious events: 79 serious events

Other events: 185 other events

Deaths: 0 deaths

Bevacizumab + FOLFIRI

Serious events: 87 serious events

Other events: 181 other events

Deaths: 0 deaths

Serious adverse events

Measure	Bevacizumab + mFOLFOX6 n=185 participants at risk Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=183 participants at risk Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Cardiac disorders Left ventricular dysfunction	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Cardiac disorders Myocardial infarction	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Diarrhoea	3.2% 6/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	1.1% 2/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Small intestinal obstruction	2.7% 5/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	3.3% 6/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Rectal haemorrhage	2.2% 4/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Abdominal pain	1.6% 3/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	3.8% 7/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Intestinal obstruction	1.6% 3/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	1.6% 3/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Vomiting	1.6% 3/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	2.2% 4/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Constipation	1.1% 2/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Dysphagia	1.1% 2/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Large intestine perforation	1.1% 2/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Nausea	1.1% 2/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Oesophagitis	1.1% 2/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	1.1% 2/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Abdominal pain lower	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Ascites	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Enteritis	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Ileal perforation	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Large intestinal haemorrhage	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Neutropenic colitis	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Oesophageal motility disorder	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Oesophageal varices haemorrhage	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Pneumoperitoneum	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Small intestinal perforation	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Abdominal distension	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	1.1% 2/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Anal fistula	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Colitis	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	1.1% 2/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Duodenitis	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Enterovesical fistula	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Gastric haemorrhage	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Ileus	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	1.1% 2/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Large intestinal obstruction	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	1.1% 2/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Pancreatitis	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Reflux gastritis	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Sepsis	2.2% 4/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	1.6% 3/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Pneumonia	1.6% 3/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	3.8% 7/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Cellulitis	1.1% 2/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Septic shock	1.1% 2/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Upper respiratory tract infection	1.1% 2/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Abdominal abscess	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Abdominal infection	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Appendicitis	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Bronchitis	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Candida sepsis	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Diverticulitis	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Endocarditis	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Infection	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Lung infection	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Respiratory tract infection	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Subcutaneous abscess	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Urinary tract infection	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Urosepsis	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Device related infection	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	1.1% 2/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Gastroenteritis	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Gastroenteritis viral	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Kidney infection	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Lower respiratory tract infection	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Neutropenic sepsis	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Perineal abscess	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Pneumonia bacterial	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Pneumonia parainfluenzae viral	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	4.9% 9/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	4.9% 9/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	1.1% 2/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory distress	1.1% 2/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Respiratory, thoracic and mediastinal disorders Hiccups	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary thrombosis	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary artery thrombosis	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Metabolism and nutrition disorders Dehydration	4.3% 8/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	2.7% 5/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Metabolism and nutrition disorders Decreased appetite	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Metabolism and nutrition disorders Diabetes mellitus	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Metabolism and nutrition disorders Failure to thrive	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Metabolism and nutrition disorders Hyponatraemia	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	1.1% 2/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Metabolism and nutrition disorders Malnutrition	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Metabolism and nutrition disorders Metabolic alkalosis	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
General disorders Chest pain	1.6% 3/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	2.2% 4/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
General disorders Pyrexia	1.6% 3/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	2.2% 4/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
General disorders Device dislocation	1.1% 2/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
General disorders Asthenia	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
General disorders Chills	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
General disorders Mucosal inflammation	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
General disorders Multi-organ failure	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
General disorders Peripheral swelling	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
General disorders Systemic inflammatory response syndrome	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
General disorders Device malfunction	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
General disorders Fatigue	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	1.6% 3/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
General disorders Gait disturbance	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
General disorders Localised oedema	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Vascular disorders Hypotension	2.7% 5/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Vascular disorders Hypertension	1.6% 3/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	3.3% 6/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Vascular disorders Arterial thrombosis	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Vascular disorders Deep vein thrombosis	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	2.2% 4/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Vascular disorders Embolism venous	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Vascular disorders Venous thrombosis	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Vascular disorders Jugular vein thrombosis	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Vascular disorders Thrombosis	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	1.6% 3/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Blood and lymphatic system disorders Febrile neutropenia	1.1% 2/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	2.2% 4/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Blood and lymphatic system disorders Anaemia	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Blood and lymphatic system disorders Immune thrombocytopenic purpura	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Blood and lymphatic system disorders Neutropenia	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	1.1% 2/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Blood and lymphatic system disorders Pancytopenia	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Cardiac disorders Atrial flutter	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Cardiac disorders Cardio-respiratory arrest	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Cardiac disorders Supraventricular tachycardia	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Cardiac disorders Atrial fibrillation	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	1.6% 3/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Cardiac disorders Atrial thrombosis	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Injury, poisoning and procedural complications Infusion related reaction	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Injury, poisoning and procedural complications Laceration	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Injury, poisoning and procedural complications Stoma site haemorrhage	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Injury, poisoning and procedural complications Toxicity to various agents	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Injury, poisoning and procedural complications Wound dehiscence	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Injury, poisoning and procedural complications Abdominal wound dehiscence	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Injury, poisoning and procedural complications Intestinal anastomosis complication	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Nervous system disorders Aphonia	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Nervous system disorders Ataxia	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Nervous system disorders Cerebrovascular accident	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Nervous system disorders Seizure	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Nervous system disorders Syncope	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	1.1% 2/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Nervous system disorders Haemorrhage intracranial	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Nervous system disorders Ischaemic stroke	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Nervous system disorders Thrombotic stroke	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Hepatobiliary disorders Cholecystitis	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Hepatobiliary disorders Cholecystitis acute	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Hepatobiliary disorders Hyperbilirubinaemia	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Hepatobiliary disorders Ischaemic hepatitis	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Hepatobiliary disorders Biloma	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Hepatobiliary disorders Cholangitis	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Hepatobiliary disorders Cholecystitis chronic	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Hepatobiliary disorders Cholelithiasis	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Hepatobiliary disorders Hepatic steatosis	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Hepatobiliary disorders Hepatitis	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Hepatobiliary disorders Jaundice	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Investigations Platelet count decreased	1.1% 2/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Investigations Weight decreased	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Investigations Blood bilirubin increased	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	1.1% 2/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Musculoskeletal and connective tissue disorders Muscular weakness	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Musculoskeletal and connective tissue disorders Polyarthritis	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Renal and urinary disorders Acute kidney injury	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	1.1% 2/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Renal and urinary disorders Proteinuria	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Renal and urinary disorders Renal failure	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Psychiatric disorders Confusional state	0.54% 1/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Psychiatric disorders Mental status changes	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	1.1% 2/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Surgical and medical procedures Colostomy	0.00% 0/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.

Other adverse events

Measure	Bevacizumab + mFOLFOX6 n=185 participants at risk Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, oxaliplatin as 85 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.	Bevacizumab + FOLFIRI n=183 participants at risk Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m\^2, irinotecan as 180 mg/m\^2, and 5-fluorouracil as 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m\^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
Gastrointestinal disorders Diarrhoea	53.5% 99/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	67.2% 123/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Nausea	57.3% 106/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	59.6% 109/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Constipation	34.1% 63/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	35.5% 65/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Vomiting	31.4% 58/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	31.1% 57/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Abdominal pain	21.1% 39/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	29.5% 54/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Stomatitis	18.9% 35/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	20.8% 38/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Gastrooesophageal reflux disease	9.2% 17/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	9.8% 18/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Dyspepsia	10.3% 19/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	7.7% 14/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Rectal haemorrhage	5.9% 11/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	9.8% 18/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Abdominal pain upper	4.3% 8/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	8.2% 15/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Oral pain	4.3% 8/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	7.7% 14/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Haemorrhoids	3.2% 6/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	8.7% 16/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Proctalgia	3.8% 7/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	7.1% 13/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Dry mouth	3.8% 7/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	6.0% 11/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Abdominal distension	2.7% 5/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	6.6% 12/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Gastrointestinal disorders Dysphagia	5.4% 10/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	1.1% 2/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
General disorders Fatigue	56.8% 105/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	56.8% 104/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
General disorders Mucosal inflammation	20.0% 37/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	27.9% 51/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
General disorders Pyrexia	9.7% 18/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	15.8% 29/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
General disorders Asthenia	11.4% 21/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	9.8% 18/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
General disorders Oedema peripheral	9.7% 18/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	9.8% 18/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
General disorders Temperature intolerance	18.4% 34/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.55% 1/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
General disorders Chest pain	8.1% 15/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	5.5% 10/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
General disorders Chills	5.4% 10/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	5.5% 10/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
General disorders Influenza like illness	5.4% 10/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	3.3% 6/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Nervous system disorders Neuropathy peripheral	45.9% 85/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	12.6% 23/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Nervous system disorders Headache	16.8% 31/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	20.8% 38/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Nervous system disorders Dysgeusia	17.8% 33/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	16.9% 31/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Nervous system disorders Paraesthesia	18.9% 35/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	8.2% 15/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Nervous system disorders Peripheral sensory neuropathy	18.9% 35/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	6.6% 12/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Nervous system disorders Dizziness	8.1% 15/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	15.3% 28/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	22.2% 41/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	32.2% 59/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	16.8% 31/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	15.8% 29/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	15.1% 28/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	14.2% 26/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	6.5% 12/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	11.5% 21/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Respiratory, thoracic and mediastinal disorders Dysphonia	7.6% 14/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	9.8% 18/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Respiratory, thoracic and mediastinal disorders Hiccups	4.3% 8/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	7.7% 14/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.9% 11/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	4.4% 8/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Metabolism and nutrition disorders Decreased appetite	30.3% 56/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	30.1% 55/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	19.5% 36/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	18.0% 33/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Metabolism and nutrition disorders Dehydration	15.1% 28/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	14.8% 27/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	4.9% 9/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	12.6% 23/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Metabolism and nutrition disorders Hyponatraemia	4.3% 8/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	8.2% 15/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Skin and subcutaneous tissue disorders Alopecia	14.1% 26/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	33.3% 61/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Skin and subcutaneous tissue disorders Dry skin	14.6% 27/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	14.2% 26/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Skin and subcutaneous tissue disorders Rash	10.3% 19/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	14.2% 26/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	13.0% 24/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	9.8% 18/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	9.7% 18/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	7.1% 13/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	5.9% 11/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	4.9% 9/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Skin and subcutaneous tissue disorders Hyperhidrosis	1.1% 2/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	5.5% 10/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Blood and lymphatic system disorders Neutropenia	35.1% 65/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	47.0% 86/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Blood and lymphatic system disorders Anaemia	13.5% 25/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	18.6% 34/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	23.8% 44/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	7.1% 13/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	11.9% 22/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	13.7% 25/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	11.4% 21/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	12.6% 23/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	11.9% 22/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	10.4% 19/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	9.2% 17/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	6.0% 11/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	3.8% 7/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	6.0% 11/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Investigations Weight decreased	17.8% 33/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	15.8% 29/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Investigations Neutrophil count decreased	17.8% 33/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	12.6% 23/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Investigations Platelet count decreased	13.0% 24/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	1.6% 3/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Investigations White blood cell count decreased	8.1% 15/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	4.9% 9/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Psychiatric disorders Insomnia	15.7% 29/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	19.1% 35/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Psychiatric disorders Depression	13.0% 24/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	9.8% 18/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Psychiatric disorders Anxiety	10.3% 19/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	10.9% 20/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Vascular disorders Hypertension	33.0% 61/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	29.5% 54/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Urinary tract infection	9.7% 18/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	10.9% 20/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Upper respiratory tract infection	8.1% 15/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	9.8% 18/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Infections and infestations Sinusitis	4.9% 9/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	7.1% 13/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Renal and urinary disorders Proteinuria	20.5% 38/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	21.3% 39/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Eye disorders Vision blurred	7.0% 13/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	6.6% 12/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Eye disorders Lacrimation increased	2.2% 4/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	5.5% 10/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Injury, poisoning and procedural complications Infusion related reaction	8.1% 15/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	4.4% 8/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.
Immune system disorders Hypersensitivity	5.4% 10/185 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.	0.00% 0/183 • Serious Adverse Events (AEs): Baseline until 3 months after last dose or study discontinuation/termination (up to 45 months overall); Other AEs: Baseline until 28 days after last dose or study discontinuation/termination (up to 45 months overall). Safety Population: All randomized participants who received at least one partial or complete dose of study drug.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER