Trial Outcomes & Findings for A Study Comparing MB02 and Avastin® in Subjects With Stage IIIB/IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC) (NCT NCT03296163)

Last Updated: 2021-04-26

Results Overview

Objective response rate was assigned for a subject if the subject displayed either complete response (CR) or partial response (PR) per RECIST version 1.1 at Week 18, as assessed by independent radiological review committee (IRC). Overall Response (OR) = CR + PR.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

627 participants

Primary outcome timeframe

18 weeks from randomisation

Results posted on

2021-04-26

Participant Flow

A total of 627 subjects were randomized and assigned to one of the study arms. Two subjects in the MB02 arm failed screening but were randomized in error. These subjects did not receive treatment. Another two subjects did not receive MB02 treatment due to death (one subject) and unacceptable toxicity (one subject). Two subjects in the European (EU)-approved bevacizumab did not receive study treatment due to investigator decision (one subject) and unacceptable toxicity (one subject).

Participant milestones

Participant milestones
Measure	MB02 (Bevacizumab Biosimilar Drug) MB02 (Bevacizumab Biosimilar Drug) + Carboplatin/Paclitaxel MB02 (Bevacizumab Biosimilar Drug): 15 mg/kg IV every 3 weeks on Day 1 Carboplatin: Carboplatin AUC 6 IV every 3 weeks on Day 1 for 6 cycles Paclitaxel: Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 6 cycles	EU-approved Avastin® EU-approved Avastin® + Carboplatin/Paclitaxel EU-approved Avastin®: 15 mg/kg IV every 3 weeks on Day 1 Carboplatin: Carboplatin AUC 6 IV every 3 weeks on Day 1 for 6 cycles Paclitaxel: Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 6 cycles
Combination Therapy STARTED	315	312
Combination Therapy COMPLETED	207	220
Combination Therapy NOT COMPLETED	108	92
Monotherapy STARTED	207	220
Monotherapy COMPLETED	68	74
Monotherapy NOT COMPLETED	139	146

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study Comparing MB02 and Avastin® in Subjects With Stage IIIB/IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MB02 (Bevacizumab Biosimilar Drug) n=315 Participants MB02 (Bevacizumab Biosimilar Drug) + Carboplatin/Paclitaxel MB02 (Bevacizumab Biosimilar Drug): 15 mg/kg IV every 3 weeks on Day 1 Carboplatin: Carboplatin AUC 6 IV every 3 weeks on Day 1 for 6 cycles Paclitaxel: Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 6 cycles	EU-approved Avastin® n=312 Participants EU-approved Avastin® + Carboplatin/Paclitaxel EU-approved Avastin®: 15 mg/kg IV every 3 weeks on Day 1 Carboplatin: Carboplatin AUC 6 IV every 3 weeks on Day 1 for 6 cycles Paclitaxel: Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 6 cycles	Total n=627 Participants Total of all reporting groups
Age, Continuous	61.0 years n=5 Participants	61.0 years n=7 Participants	61.0 years n=5 Participants
Sex: Female, Male Female	122 Participants n=5 Participants	122 Participants n=7 Participants	244 Participants n=5 Participants
Sex: Female, Male Male	193 Participants n=5 Participants	190 Participants n=7 Participants	383 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	71 Participants n=5 Participants	54 Participants n=7 Participants	125 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	243 Participants n=5 Participants	256 Participants n=7 Participants	499 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Body surface area (BSA)	1.780 m^2 n=5 Participants	1.790 m^2 n=7 Participants	1.780 m^2 n=5 Participants

PRIMARY outcome

Timeframe: 18 weeks from randomisation

Population: Primary efficacy analysis was done in the intention-to-treat (ITT) population.

Outcome measures

Outcome measures
Measure	MB02 (Bevacizumab Biosimilar Drug) n=315 Participants MB02 (Bevacizumab Biosimilar Drug) + Carboplatin/Paclitaxel MB02 (Bevacizumab Biosimilar Drug): 15 mg/kg IV every 3 weeks on Day 1 Carboplatin: Carboplatin AUC 6 IV every 3 weeks on Day 1 for 6 cycles Paclitaxel: Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 6 cycles	EU-approved Avastin® n=312 Participants EU-approved Avastin® + Carboplatin/Paclitaxel EU-approved Avastin®: 15 mg/kg IV every 3 weeks on Day 1 Carboplatin: Carboplatin AUC 6 IV every 3 weeks on Day 1 for 6 cycles Paclitaxel: Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 6 cycles
Objective Response Rate (ORR) at Week 18	40.3 Percentage of participants Interval 34.9 to 46.0	44.6 Percentage of participants Interval 39.0 to 50.3

SECONDARY outcome

Timeframe: At Week 52 from randomisation

Progression-free survival was defined as the time from randomization to subsequent confirmed progression per RECIST version 1.1, or death (whichever occurred first), measured in weeks and months. For PFS assessment clinical progression (i.e., treatment discontinuation due to progression of disease) was also considered as an event.

Outcome measures

Outcome measures
Measure	MB02 (Bevacizumab Biosimilar Drug) n=315 Participants MB02 (Bevacizumab Biosimilar Drug) + Carboplatin/Paclitaxel MB02 (Bevacizumab Biosimilar Drug): 15 mg/kg IV every 3 weeks on Day 1 Carboplatin: Carboplatin AUC 6 IV every 3 weeks on Day 1 for 6 cycles Paclitaxel: Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 6 cycles	EU-approved Avastin® n=312 Participants EU-approved Avastin® + Carboplatin/Paclitaxel EU-approved Avastin®: 15 mg/kg IV every 3 weeks on Day 1 Carboplatin: Carboplatin AUC 6 IV every 3 weeks on Day 1 for 6 cycles Paclitaxel: Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 6 cycles
Progression-free Survival (PFS)	36.0 weeks Interval 33.0 to 36.43	37.3 weeks Interval 36.14 to 45.14

SECONDARY outcome

Timeframe: At Week 52 from randomisation

Overall survival was defined as the time from randomization to subsequent death, measured in weeks and months.

Outcome measures

Outcome measures
Measure	MB02 (Bevacizumab Biosimilar Drug) n=315 Participants MB02 (Bevacizumab Biosimilar Drug) + Carboplatin/Paclitaxel MB02 (Bevacizumab Biosimilar Drug): 15 mg/kg IV every 3 weeks on Day 1 Carboplatin: Carboplatin AUC 6 IV every 3 weeks on Day 1 for 6 cycles Paclitaxel: Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 6 cycles	EU-approved Avastin® n=312 Participants EU-approved Avastin® + Carboplatin/Paclitaxel EU-approved Avastin®: 15 mg/kg IV every 3 weeks on Day 1 Carboplatin: Carboplatin AUC 6 IV every 3 weeks on Day 1 for 6 cycles Paclitaxel: Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 6 cycles
Overall Survival (OS)	NA weeks NA: insufficient number of participants with events	NA weeks NA: insufficient number of participants with events

SECONDARY outcome

Timeframe: Week 1 to week 52

Population: Safety analyses were performed in the Safety population, which consisted of all subjects who received at least 1 administration of investigational medicinal product.

Comparison of Safety profile. Safety was monitored by incidence of adverse events (AEs). AEs were coded as per MedDRA (version 20.1) and severity was graded according to NCI-CTCAE (version 4.03);

Outcome measures

Outcome measures
Measure	MB02 (Bevacizumab Biosimilar Drug) n=311 Participants MB02 (Bevacizumab Biosimilar Drug) + Carboplatin/Paclitaxel MB02 (Bevacizumab Biosimilar Drug): 15 mg/kg IV every 3 weeks on Day 1 Carboplatin: Carboplatin AUC 6 IV every 3 weeks on Day 1 for 6 cycles Paclitaxel: Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 6 cycles	EU-approved Avastin® n=310 Participants EU-approved Avastin® + Carboplatin/Paclitaxel EU-approved Avastin®: 15 mg/kg IV every 3 weeks on Day 1 Carboplatin: Carboplatin AUC 6 IV every 3 weeks on Day 1 for 6 cycles Paclitaxel: Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 6 cycles
Incidence of Treatment-emergent Adverse Events (TEAEs) with ≥1 TEAE	288 participants	288 participants
Incidence of Treatment-emergent Adverse Events (TEAEs) with ≥1 Grade 3 or 4 TEAE	131 participants	125 participants
Incidence of Treatment-emergent Adverse Events (TEAEs) with ≥1 treatment-related TEAE	264 participants	270 participants
Incidence of Treatment-emergent Adverse Events (TEAEs) with ≥1 Grade 3 or 4 treatment-related TEAE	98 participants	91 participants
Incidence of Treatment-emergent Adverse Events (TEAEs) with at least one Serious TEAE	58 participants	54 participants
Incidence of Treatment-emergent Adverse Events (TEAEs) with ≥1 TEAE leading to discontinuation	72 participants	63 participants
Incidence of Treatment-emergent Adverse Events (TEAEs) with ≥1 treatment-related TEAE leading to discontinuation	42 participants	33 participants

SECONDARY outcome

Timeframe: At Weeks 1, 4, 10, 19, 34 and 52 from randomization and, at the End of Treatment Visit if, an ADA sample has not been collected within the previous 3 weeks

Population: Immunogenicity was assessed in the Safety population.

Incidence of anti-drug antibodies (ADA) and neutralizing ADAs (NAb). Analyses of ADA incidence rate, antibody titer, and neutralizing antibodies (NAb) (following the recommended 3-tier approach) were performed.

Outcome measures

Outcome measures
Measure	MB02 (Bevacizumab Biosimilar Drug) n=311 Participants MB02 (Bevacizumab Biosimilar Drug) + Carboplatin/Paclitaxel MB02 (Bevacizumab Biosimilar Drug): 15 mg/kg IV every 3 weeks on Day 1 Carboplatin: Carboplatin AUC 6 IV every 3 weeks on Day 1 for 6 cycles Paclitaxel: Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 6 cycles	EU-approved Avastin® n=310 Participants EU-approved Avastin® + Carboplatin/Paclitaxel EU-approved Avastin®: 15 mg/kg IV every 3 weeks on Day 1 Carboplatin: Carboplatin AUC 6 IV every 3 weeks on Day 1 for 6 cycles Paclitaxel: Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 6 cycles
Immunogenicity Assessments (Anti-drug Antibodies [ADA] and Neutralizing Antibodies [NAb]) ADA positive	53 participants	50 participants
Immunogenicity Assessments (Anti-drug Antibodies [ADA] and Neutralizing Antibodies [NAb]) NAb positive	10 participants	13 participants
Immunogenicity Assessments (Anti-drug Antibodies [ADA] and Neutralizing Antibodies [NAb]) NO seroconversion	239 participants	247 participants

Adverse Events

MB02 (Bevacizumab Biosimilar Drug)

Serious events: 58 serious events

Other events: 288 other events

Deaths: 23 deaths

EU-approved Avastin®

Serious events: 54 serious events

Other events: 288 other events

Deaths: 24 deaths

Serious adverse events

Other adverse events

Additional Information

Susana Millan

mAbxience Research SL

Phone: +34917711500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	MB02 (Bevacizumab Biosimilar Drug) n=311 participants at risk MB02 (Bevacizumab Biosimilar Drug) + Carboplatin/Paclitaxel MB02 (Bevacizumab Biosimilar Drug): 15 mg/kg IV every 3 weeks on Day 1 Carboplatin: Carboplatin AUC 6 IV every 3 weeks on Day 1 for 6 cycles Paclitaxel: Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 6 cycles	EU-approved Avastin® n=310 participants at risk EU-approved Avastin® + Carboplatin/Paclitaxel EU-approved Avastin®: 15 mg/kg IV every 3 weeks on Day 1 Carboplatin: Carboplatin AUC 6 IV every 3 weeks on Day 1 for 6 cycles Paclitaxel: Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 6 cycles
Infections and infestations Pneumonia	2.6% 8/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	2.6% 8/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Infections and infestations Empyema	0.96% 3/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.00% 0/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Infections and infestations Gastroenteritis	0.32% 1/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.65% 2/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Infections and infestations Sepsis	0.64% 2/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.00% 0/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Infections and infestations Brain abscess	0.32% 1/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.00% 0/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Infections and infestations Chronic sinusitis	0.00% 0/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.32% 1/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Infections and infestations Dengue fever	0.32% 1/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.00% 0/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Infections and infestations Lung abscess	0.32% 1/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.00% 0/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Infections and infestations Neutropenic sepsis	0.32% 1/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.00% 0/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Infections and infestations Osteomyelitis	0.00% 0/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.32% 1/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Infections and infestations Respiratory tract infection viral	0.00% 0/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.32% 1/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Infections and infestations Septic shock	0.00% 0/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.32% 1/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Infections and infestations Urinary tract infection	0.00% 0/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.32% 1/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Blood and lymphatic system disorders Febrile neutropenia	1.3% 4/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	2.3% 7/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Blood and lymphatic system disorders Neutropenia	0.96% 3/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	1.9% 6/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Blood and lymphatic system disorders Anemia	0.32% 1/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.65% 2/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Blood and lymphatic system disorders Thrombocytopenia	0.64% 2/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.00% 0/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Blood and lymphatic system disorders Leukocytosis	0.32% 1/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.00% 0/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
General disorders General physical health deterioration	0.96% 3/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	1.9% 6/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
General disorders Pyrexia	0.64% 2/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.32% 1/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
General disorders Asthenia	0.00% 0/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.65% 2/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
General disorders Death	0.64% 2/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.00% 0/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
General disorders Fatigue	0.00% 0/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.65% 2/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
General disorders Sudden death	0.64% 2/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.00% 0/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
General disorders Disease progression	0.32% 1/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.00% 0/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
General disorders Non-cardiac chest pain	0.32% 1/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.00% 0/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.9% 6/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	1.3% 4/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.32% 1/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.65% 2/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Respiratory, thoracic and mediastinal disorders Pulmonary hemorrhage	0.32% 1/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.32% 1/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.65% 2/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.32% 1/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.32% 1/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Respiratory, thoracic and mediastinal disorders Hemoptysis	0.32% 1/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.00% 0/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.32% 1/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.00% 0/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Respiratory, thoracic and mediastinal disorders Pneumothorax spontaneous	0.00% 0/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.32% 1/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Nervous system disorders Dizziness	0.00% 0/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.65% 2/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Respiratory, thoracic and mediastinal disorders Hemorrhage intracranial	0.64% 2/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.00% 0/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Nervous system disorders Ischemic stroke	0.32% 1/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.32% 1/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Nervous system disorders Ataxia	0.00% 0/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.32% 1/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Nervous system disorders Cerebral ischemia	0.32% 1/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	0.00% 0/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).

Other adverse events
Measure	MB02 (Bevacizumab Biosimilar Drug) n=311 participants at risk MB02 (Bevacizumab Biosimilar Drug) + Carboplatin/Paclitaxel MB02 (Bevacizumab Biosimilar Drug): 15 mg/kg IV every 3 weeks on Day 1 Carboplatin: Carboplatin AUC 6 IV every 3 weeks on Day 1 for 6 cycles Paclitaxel: Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 6 cycles	EU-approved Avastin® n=310 participants at risk EU-approved Avastin® + Carboplatin/Paclitaxel EU-approved Avastin®: 15 mg/kg IV every 3 weeks on Day 1 Carboplatin: Carboplatin AUC 6 IV every 3 weeks on Day 1 for 6 cycles Paclitaxel: Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 6 cycles
Skin and subcutaneous tissue disorders Alopecia	49.8% 155/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	52.6% 163/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Blood and lymphatic system disorders Anemia	32.5% 101/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	30.3% 94/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Blood and lymphatic system disorders Thrombocytopenia	13.2% 41/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	13.5% 42/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Blood and lymphatic system disorders Neutropenia	10.9% 34/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	14.5% 45/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Blood and lymphatic system disorders Leukopenia	7.7% 24/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	5.8% 18/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Nervous system disorders Neuropathy peripheral	12.2% 38/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	13.2% 41/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Nervous system disorders Peripheral sensory neuropathy	7.1% 22/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	7.4% 23/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Nervous system disorders Paresthesia	6.8% 21/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	4.2% 13/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
General disorders Fatigue	12.5% 39/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	11.6% 36/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
General disorders Asthenia	12.5% 39/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	9.4% 29/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
General disorders General physical health deterioration	7.4% 23/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	9.4% 29/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Investigations Weight decreased	7.4% 23/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	8.7% 27/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Investigations Platelet count decreased	8.4% 26/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	6.1% 19/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Investigations Alanine aminotransferase increased	4.8% 15/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	6.8% 21/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Investigations Aspartate aminotransferase increased	4.5% 14/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	7.1% 22/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Investigations Neutrophil count decreased	5.8% 18/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	5.8% 18/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Gastrointestinal disorders Nausea	15.1% 47/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	14.2% 44/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Gastrointestinal disorders Diarrhea	9.3% 29/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	8.7% 27/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Gastrointestinal disorders Vomiting	7.1% 22/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	3.5% 11/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Musculoskeletal and connective tissue disorders Myalgia	7.4% 23/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	9.7% 30/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Musculoskeletal and connective tissue disorders Arthralgia	6.1% 19/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	6.5% 20/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Infections and infestations Respiratory tract infection viral	5.1% 16/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	5.2% 16/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Respiratory, thoracic and mediastinal disorders Cough	6.4% 20/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	7.1% 22/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Metabolism and nutrition disorders Decreased appetite	4.5% 14/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	6.5% 20/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Vascular disorders Hypertension	7.7% 24/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	8.4% 26/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).
Renal and urinary disorders Proteinuria	5.8% 18/311 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).	8.1% 25/310 • Throughout the study completion. An average of two years (from the beginning of the study at 06-February-2018 till last patient last visit in 27-February-2020). Coded according to Medical Dictionary for Regulatory Activities (version 20.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 4.03). Table for "Other Adverse events" includes serious and non-serious events. Six (MB02: 4; EU-approved Avastin: 2) out of the 627 subjects randomized did not received treatment. Therefore, the "total number of participants at risk" comprised 621 subjects (MB02: 311 subjects; EU-approved Avastin:310).