A Study Comparing SB8 and Avastin® in Patients With Advanced Non-squamous Non-small Cell Lung Cancer

The best ORR was defined as the proportion of subjects whose best overall response was either Complete Response (CR) or Partial Response (PR) according to RECIST v1.1 during the induction treatment period by 24 weeks. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Time frame: 24 weeks from randomisation

Population: The Full Analysis Set consisted of all randomised subjects. The subjects were analysed based on the treatment they were randomised to by intention-to-treat principle. However, subjects who did not qualify for randomisation and were inadvertently randomised into the study were excluded from FAS, provided these subjects did not receive any IP, and there was one subject who met these criteria. So, there is a difference between Started in Participant Flow module and Analysis Population.

DoR in subjects with response from documented tumour response until disease progression up to 12 months from randomisation of the last subject

Time frame: from documented tumour response until disease progression up to 12 months from randomisation of the last subject

Population: Full Analysis Set (FAS): Consisted of all randomised subjects. The subjects were analysed based on the treatment they were randomised to by intention-to-treat principle.~Per-protocol Set (PPS): Consisted of all FAS subjects who completed at least first 2 cycles of combination chemotherapy with a tumour assessment and did not have any major protocol deviations that impacted the primary efficacy assessment.

Incidence of anti-drug (bevacizumab) antibodies (ADA) The incidence of overall ADA results (i.e. Positive, Negative, Inconclusive) was presented by treatment group at Cycle 7 and the end of treatment (EOT). Overall ADA result was defined as below: * 'Positive' for a subject with treatment-induced or treatment-boosted ADA, where treatment-induced ADA indicated at least one positive result after pre-dose of Cycle 1 for subjects with negative ADA at pre-dose of Cycle 1, and treatment-boosted ADA indicated at least one positive result with higher titre level compared to pre-dose of Cycle 1 after pre-dose of Cycle 1 for subjects with positive ADA at pre-dose of Cycle 1. * 'Negative' for a subject without positive ADA until Cycle 7 and EOT. * 'Inconclusive' for a subject with positive ADA at Cycle 1 and without positive result with higher titre level observed after pre-dose of Cycle 1 up to Cycle 7 and EOT.

Time frame: Up to 21 weeks (Cycle 1,3,5, 7 and EOT visit. Each cycle is 21 days.), approximately 24 months from study initiation.

Population: The analysis was performed using the Safety Set (SAF). The SAF consisted of all subjects who received the study drug at least once. This analysis set was used for the safety analyses. The subjects were analysed based on the treatment they received.~There were 4 subjects in Avastin group and 1 subject in SB8 group who had not received any IP or non-IP treatment.

Incidence of anti-drug (bevacizumab) antibodies (ADA) - neutralizing antibodies (NAb) The analysis was performed using the Safety Set (SAF). Overall Number of Participants Analyzed represents the number of subjects in SAF. The total number is not the sum of the number of subjects of each visits, since NAb results only for subjects with ADA positive against SB8 or Avastin were used for the summary. Number Analyzed of each visit is equal to the number of subjects with ADA positive of each visit, which is displayed in 8. Secondary Outcome: Immunogenicity Assessments (Anti-drug Antibodies).

Time frame: Up to 21 weeks (Cycle 1,3,5, 7 and EOT visit. Each cycle is 21 days.), approximately 24 months from study initiation.

Population: The analysis was performed using the Safety Set (SAF). The SAF consisted of all subjects who received the study drug at least once. This analysis set was used for the safety analyses. The subjects were analysed based on the treatment they received.~There were 4 subjects in Avastin group and 1 subject in SB8 group who had not received any IP or non-IP treatment.

After the end of treatment (EOT) visit, SAEs should be reported to the Sponsor if the Investigator becomes aware of them. Severity Grade of NCI-CTCAE v4.03 Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL) (Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc.) Grade 3: Severe or medically significant but not immediately life-threatening; hospitalisation or prolongation of hospitalisation indicated; disabling; limiting self-care ADL (Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden.) Grade 4: Life-threatening consequences; urgent intervention indicated Grade 5: Death related to AE

Time frame: AEs were reported from the time the informed consent form (ICF) was signed until the EOT visit, approximately 24 months from study initiation.

Population: Safety Set (SAF): The Safety Set consisted of all subjects who received the study drug at least once.

OS was defined as the time from the date of randomisation to the date of death regardless of the cause of death. Subjects who were alive at the time of analysis were censored at the date of last known alive.

Time frame: from the date of randomisation to the date of death up to 12 months from randomisation of the last subject

Population: Full Analysis Set (FAS): Consisted of all randomised subjects. The subjects were analysed based on the treatment they were randomised to by intention-to-treat principle.~Per-protocol Set (PPS): Consisted of all FAS subjects who completed at least first 2 cycles of combination chemotherapy with a tumour assessment and did not have any major protocol deviations that impacted the primary efficacy assessment.

Maximum Plasma Concentration (Cmax) at selected cycles (i.e., Cycle 1, 3, 5 and 7)

Time frame: Up to 21 weeks (Cycle 1,3,5 and 7. Each cycle is 21 days.)

Population: Pharmacokinetic Population (PK Population): This set consisted of subjects allocated to PK sub-study who had at least one measured serum concentration of bevacizumab.~PK analyses were performed on the PK population. The number of participants analyzed in each Cycle is the number of participants in PK population with non-missing values or without protocol deviation for PK blood sampling at the cycle.

Ctrough at selected cycles (i.e., Cycle 1, 3, 5 and 7)

Time frame: Up to 21 weeks (Cycle 1,3,5 and 7. Each cycle is 21 days.)

Population: Pharmacokinetic Population (PK Population): This set consisted of subjects allocated to PK sub-study who had at least one measured serum concentration of bevacizumab.~PK analyses were performed on the PK population. The number of participants analyzed in each Cycle is the number of participants in PK population with non-missing values or without protocol deviation for PK blood sampling at the cycle.

PFS is defined as the time from the date of Randomisation to the date of disease progression (progressive disease \[PD\]) or death regardless of the cause of death. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

Time frame: from the date of randomisation to the date of disease progression or death up to 12 months from randomisation of the last subject

Population: Full Analysis Set (FAS): Consisted of all randomised subjects. The subjects were analysed based on the treatment they were randomised to by intention-to-treat principle. Per-protocol Set (PPS): Consisted of all FAS subjects who completed at least first 2 cycles of combination chemotherapy with a tumour assessment and did not have any major protocol deviations that impacted the primary efficacy assessment.

Best Objective Response Rate (ORR) by 11 weeks and 17 weeks

Time frame: 11 weeks and 17 weeks from randomisation

Population: Full Analysis Set (FAS): Consisted of all randomised subjects. The subjects were analysed based on the treatment they were randomised to by intention-to-treat principle.~Per-protocol Set (PPS): Consisted of all FAS subjects who completed at least first 2 cycles of combination chemotherapy with a tumour assessment and did not have any major protocol deviations that impacted the primary efficacy assessment.