Trial Outcomes & Findings for To Compare Efficacy and Safety Between CT-P10 and Rituxan in Patients With Low Tumour Burden Follicular Lymphoma (NCT NCT02260804)

Last Updated: 2021-04-08

Results Overview

ORR was defined as the proportion of patients with the best response of complete response (CR), unconfirmed CR (CRu), or partial response (PR) by central review. Per 1999 IWG criteria, the disease status was assessed by using contrasted CT and/or MRI, and CR, CRu, and PR were defined as followings; CR=Disappearance of all clinical/radiographic evidence of disease: regression of lymph nodes to normal size, absence of B-symptoms, bone marrow involvement, and organomegaly, and normal LDH level; CRu=Regression of measurable disease: \>75% decrease in SPD of target lesions and in each target lesions. no increase in the size of non-target lesions, neither new lesion nor organomegaly measured; PR=Regression of measurable disease: ≥50% decrease in SPD of target lesions and no evidence of disease progression.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

258 participants

Primary outcome timeframe

During the Month 7 (up to Maintenance Cycle 3; Week 28)

Results posted on

2021-04-08

Participant Flow

A total of 402 participants were screened for the study. Of those, 144 participants failed screening and 258 participants were enrolled in the study.

Participant milestones

Participant milestones
Measure	CT-P10 CT-P10 375mg/m2, IV, 4 cycles in induction period and additional 12 cycles in maintenance period	Rituxan Rituxan, 375mg/m2, IV, 4 cycles in induction period, Rituxan for the first 6 cycles and CT-P10 for the last 6 cycles in maintenance period.
Induction Study Period STARTED	130	128
Induction Study Period COMPLETED	128	128
Induction Study Period NOT COMPLETED	2	0
1st Year of the Maintenance Period (MP1) STARTED	123	120
1st Year of the Maintenance Period (MP1) COMPLETED	111	105
1st Year of the Maintenance Period (MP1) NOT COMPLETED	12	15
2nd Year of the Maintenance Period (MP2) STARTED	110	103
2nd Year of the Maintenance Period (MP2) COMPLETED	101	97
2nd Year of the Maintenance Period (MP2) NOT COMPLETED	9	6

Reasons for withdrawal

Reasons for withdrawal
Measure	CT-P10 CT-P10 375mg/m2, IV, 4 cycles in induction period and additional 12 cycles in maintenance period	Rituxan Rituxan, 375mg/m2, IV, 4 cycles in induction period, Rituxan for the first 6 cycles and CT-P10 for the last 6 cycles in maintenance period.
Induction Study Period Protocol Violation	2	0
1st Year of the Maintenance Period (MP1) Lack of Efficacy	6	9
1st Year of the Maintenance Period (MP1) Adverse Event	3	1
1st Year of the Maintenance Period (MP1) Physician Decision	1	3
1st Year of the Maintenance Period (MP1) Protocol Violation	1	0
1st Year of the Maintenance Period (MP1) Withdrawal by Subject	1	0
1st Year of the Maintenance Period (MP1) Death	0	1
1st Year of the Maintenance Period (MP1) Lost to Follow-up	0	1
2nd Year of the Maintenance Period (MP2) Lack of Efficacy	6	5
2nd Year of the Maintenance Period (MP2) Adverse Event	3	0
2nd Year of the Maintenance Period (MP2) Withdrawal by Subject	0	1

Baseline Characteristics

To Compare Efficacy and Safety Between CT-P10 and Rituxan in Patients With Low Tumour Burden Follicular Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CT-P10 n=130 Participants CT-P10 375mg/m2, IV, 4 cycles in induction period and additional 12 cycles in maintenance period	Rituxan n=128 Participants Rituxan, 375mg/m2, IV, 4 cycles in induction period, Rituxan for the first 6 cycles and CT-P10 for the last 6 cycles in maintenance period.	Total n=258 Participants Total of all reporting groups
Age, Continuous	57.7 years STANDARD_DEVIATION 12.68 • n=5 Participants	57.7 years STANDARD_DEVIATION 11.53 • n=7 Participants	57.7 years STANDARD_DEVIATION 12.10 • n=5 Participants
Sex: Female, Male Female	64 Participants n=5 Participants	71 Participants n=7 Participants	135 Participants n=5 Participants
Sex: Female, Male Male	66 Participants n=5 Participants	57 Participants n=7 Participants	123 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=5 Participants	10 Participants n=7 Participants	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	110 Participants n=5 Participants	116 Participants n=7 Participants	226 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants	2 Participants n=7 Participants	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: During the Month 7 (up to Maintenance Cycle 3; Week 28)

Population: The ITT population consisted of all patients enrolled and randomly assigned to receive a study drug, regardless of whether or not any study drug dosing was completed.

Outcome measures

Outcome measures
Measure	CT-P10 n=130 Participants CT-P10 375mg/m2, IV, 4 cycles in induction period and additional 12 cycles in maintenance period	Rituxan n=128 Participants Rituxan, 375mg/m2, IV, 4 cycles in induction period, Rituxan for the first 6 cycles and CT-P10 for the last 6 cycles in maintenance period.
Primary Efficacy Endpoint - Overall Response Rate by 7 Months	108 Participants	104 Participants

SECONDARY outcome

Timeframe: up to 27 months

Population: The ITT population consisted of all patients enrolled and randomly assigned to receive a study drug, regardless of whether or not any study drug dosing was completed.

ORR was defined as the proportion of patients with the best response of complete response (CR), unconfirmed CR (CRu), or partial response (PR). Per 1999 IWG criteria, the disease status was assessed by using contrasted CT and/or MRI, and CR, CRu, and PR were defined as followings; CR=Disappearance of all clinical/radiographic evidence of disease: regression of lymph nodes to normal size, absence of B-symptoms, bone marrow involvement, and organomegaly, and normal LDH level; CRu=Regression of measurable disease: \>75% decrease in SPD of target lesions and in each target lesions. no increase in the size of non-target lesions, neither new lesion nor organomegaly measured; PR=Regression of measurable disease: ≥50% decrease in SPD of target lesions and no evidence of disease progression.

Outcome measures

Outcome measures
Measure	CT-P10 n=130 Participants CT-P10 375mg/m2, IV, 4 cycles in induction period and additional 12 cycles in maintenance period	Rituxan n=128 Participants Rituxan, 375mg/m2, IV, 4 cycles in induction period, Rituxan for the first 6 cycles and CT-P10 for the last 6 cycles in maintenance period.
Secondary Efficacy Endpoint - ORR Over the Study Period	109 Participants	112 Participants

SECONDARY outcome

Timeframe: Baseline, Induction Cycle 1 (predose, 1 hr postdose), Induction Cycle 2 to 4 (predose), EOT1/EOT2 (anytime), Maintenance Cycle 1 to 2 (predose, 1hr postdose) and Maintenance Cycle 3 (predose).

Population: The PD population consisted of all patients who received at least 1 dose (full) of study drug and had at least 1 posttreatment PD result.

B-cell kinetics were demonstrated by median values of B-cell counts. Any values below the LLoQ were set as LLoQ which was 20 cells/μL.

Outcome measures

Outcome measures
Measure	CT-P10 n=128 Participants CT-P10 375mg/m2, IV, 4 cycles in induction period and additional 12 cycles in maintenance period	Rituxan n=128 Participants Rituxan, 375mg/m2, IV, 4 cycles in induction period, Rituxan for the first 6 cycles and CT-P10 for the last 6 cycles in maintenance period.
Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) Baseline	95.0 cells/uL Interval 56.0 to 171.5	120.0 cells/uL Interval 64.0 to 182.0
Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) Induction Cycle 1 (1hr after end of infusion)	20.0 cells/uL Interval 20.0 to 20.0	20.0 cells/uL Interval 20.0 to 20.0
Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) Induction Cycle 2 (predose)	20.0 cells/uL Interval 20.0 to 20.0	20.0 cells/uL Interval 20.0 to 20.0
Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) Induction Cycle 3 (predose)	20.0 cells/uL Interval 20.0 to 20.0	20.0 cells/uL Interval 20.0 to 20.0
Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) Induction Cycle 4 (predose)	20.0 cells/uL Interval 20.0 to 20.0	20.0 cells/uL Interval 20.0 to 20.0
Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) EOT1 (anytime)	20.0 cells/uL Interval 20.0 to 20.0	20.0 cells/uL Interval 20.0 to 20.0
Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) Maintenance Cycle 1 (predose)	20.0 cells/uL Interval 20.0 to 20.0	20.0 cells/uL Interval 20.0 to 20.0
Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) Maintenance Cycle 1 (1hr after end of infusion)	20.0 cells/uL Interval 20.0 to 20.0	20.0 cells/uL Interval 20.0 to 20.0
Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) Maintenance Cycle 2 (predose)	20.0 cells/uL Interval 20.0 to 20.0	20.0 cells/uL Interval 20.0 to 20.0
Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) Maintenance Cycle 2 (1hr after end of infusion)	20.0 cells/uL Interval 20.0 to 20.0	20.0 cells/uL Interval 20.0 to 20.0
Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) Maintenance Cycle 3 (predose)	20.0 cells/uL Interval 20.0 to 20.0	20.0 cells/uL Interval 20.0 to 20.0

SECONDARY outcome

Timeframe: 1, 2, 3, 4, 12, 20 weeks (predose, 1 hr post dose), EOT1/EOT2 (anytime during the day) and 28 week (predose)

Population: The PK population consisted of all patients who received at least 1 dose (full) of study drug and had at least 1 posttreatment PK result.

Outcome measures

Outcome measures
Measure	CT-P10 n=128 Participants CT-P10 375mg/m2, IV, 4 cycles in induction period and additional 12 cycles in maintenance period	Rituxan n=128 Participants Rituxan, 375mg/m2, IV, 4 cycles in induction period, Rituxan for the first 6 cycles and CT-P10 for the last 6 cycles in maintenance period.
Secondary PK Endpoints - Cmax Induction Cycle 1	212.86 μg/mL Standard Deviation 50.64	217.38 μg/mL Standard Deviation 56.33
Secondary PK Endpoints - Cmax Induction Cycle 2	283.35 μg/mL Standard Deviation 53.84	285.98 μg/mL Standard Deviation 62.26
Secondary PK Endpoints - Cmax Induction Cycle 3	327.32 μg/mL Standard Deviation 71.05	341.59 μg/mL Standard Deviation 77.95
Secondary PK Endpoints - Cmax Induction Cycle 4	373.46 μg/mL Standard Deviation 70.50	383.05 μg/mL Standard Deviation 83.86
Secondary PK Endpoints - Cmax Maintenance Cycle 1	256.97 μg/mL Standard Deviation 65.61	265.03 μg/mL Standard Deviation 53.73
Secondary PK Endpoints - Cmax Maintenance Cycle 2	239.70 μg/mL Standard Deviation 65.72	249.86 μg/mL Standard Deviation 69.02

SECONDARY outcome

Timeframe: 1, 2, 3, 4, 12, 20 weeks (predose, 1 hr post dose), EOT1/EOT2 (anytime during the day) and 28 week (predose)

Population: The PK population consisted of all patients who received at least 1 dose (full) of study drug and had at least 1 posttreatment PK result.

Outcome measures

Outcome measures
Measure	CT-P10 n=128 Participants CT-P10 375mg/m2, IV, 4 cycles in induction period and additional 12 cycles in maintenance period	Rituxan n=128 Participants Rituxan, 375mg/m2, IV, 4 cycles in induction period, Rituxan for the first 6 cycles and CT-P10 for the last 6 cycles in maintenance period.
Secondary PK Endpoints - Ctrough Induction Cycle 1	64.66 μg/mL Standard Deviation 24.88	72.94 μg/mL Standard Deviation 40.39
Secondary PK Endpoints - Ctrough Induction Cycle 2	113.23 μg/mL Standard Deviation 34.60	120.92 μg/mL Standard Deviation 36.02
Secondary PK Endpoints - Ctrough Induction Cycle 3	149.53 μg/mL Standard Deviation 43.65	161.80 μg/mL Standard Deviation 43.91
Secondary PK Endpoints - Ctrough Induction Cycle 4	34.78 μg/mL Standard Deviation 33.58	31.38 μg/mL Standard Deviation 19.15
Secondary PK Endpoints - Ctrough Maintenance Cycle 1	22.68 μg/mL Standard Deviation 37.22	21.35 μg/mL Standard Deviation 20.90
Secondary PK Endpoints - Ctrough Maintenance Cycle 2	16.96 μg/mL Standard Deviation 9.61	18.37 μg/mL Standard Deviation 10.86

SECONDARY outcome

Timeframe: Overall study period (Baseline, Month 3, 7, 13, 19 27, and every 6 months thereafter).

Population: The ITT population consisted of all patients enrolled and randomly assigned to receive a study drug, regardless of whether or not any study drug dosing was completed.

PFS was defined as the interval between randomization and disease progression/relapse by IWG 1999 (at least a 50% increase of any single nodal after smallest decrease) or death from any cause, whichever occurred first. Locally reviewed data was used for the secondary efficacy analyses.

Outcome measures

Outcome measures
Measure	CT-P10 n=130 Participants CT-P10 375mg/m2, IV, 4 cycles in induction period and additional 12 cycles in maintenance period	Rituxan n=128 Participants Rituxan, 375mg/m2, IV, 4 cycles in induction period, Rituxan for the first 6 cycles and CT-P10 for the last 6 cycles in maintenance period.
Secondary Efficacy Endpoint - Progression-free Survival (PFS) 12 months	0.93 Proportion of Participants Interval 0.87 to 0.96	0.89 Proportion of Participants Interval 0.82 to 0.93
Secondary Efficacy Endpoint - Progression-free Survival (PFS) 24 months	0.88 Proportion of Participants Interval 0.81 to 0.92	0.83 Proportion of Participants Interval 0.75 to 0.89
Secondary Efficacy Endpoint - Progression-free Survival (PFS) 36 months	0.80 Proportion of Participants Interval 0.7 to 0.87	0.68 Proportion of Participants Interval 0.54 to 0.79

SECONDARY outcome

Timeframe: Overall study period (median follow-up of 29.2 months)

Population: The ITT population consisted of all patients enrolled and randomly assigned to receive a study drug, regardless of whether or not any study drug dosing was completed.

Overall survival was defined as the interval between randomization and death from any cause. Locally reviewed data was used for the secondary efficacy analyses.

Outcome measures

Outcome measures
Measure	CT-P10 n=130 Participants CT-P10 375mg/m2, IV, 4 cycles in induction period and additional 12 cycles in maintenance period	Rituxan n=128 Participants Rituxan, 375mg/m2, IV, 4 cycles in induction period, Rituxan for the first 6 cycles and CT-P10 for the last 6 cycles in maintenance period.
Secondary Efficacy Endpoint - Overall Survival (OS) 12 months	0.98 Proportion of Participants Interval 0.93 to 0.99	0.98 Proportion of Participants Interval 0.94 to 1.0
Secondary Efficacy Endpoint - Overall Survival (OS) 24 months	0.98 Proportion of Participants Interval 0.93 to 0.99	0.98 Proportion of Participants Interval 0.94 to 1.0
Secondary Efficacy Endpoint - Overall Survival (OS) 36 months	0.98 Proportion of Participants Interval 0.93 to 0.99	0.97 Proportion of Participants Interval 0.89 to 0.99
Secondary Efficacy Endpoint - Overall Survival (OS) 42 months	0.98 Proportion of Participants Interval 0.93 to 0.99	0.97 Proportion of Participants Interval 0.89 to 0.99

SECONDARY outcome

Timeframe: Overall study period (Baseline, Month 3, 7, 13, 19 27, and every 6 months thereafter).

Population: The ITT population consisted of all patients enrolled and randomly assigned to receive a study drug, regardless of whether or not any study drug dosing was completed.

Time to progression was defined as the interval between randomization and disease progression/relapse by IWG 1999 (at least a 50% increase of any single nodal after smallest decrease) or death as a result of lymphoma, whichever occurred first. Locally reviewed data was used for the secondary efficacy analyses.

Outcome measures

Outcome measures
Measure	CT-P10 n=130 Participants CT-P10 375mg/m2, IV, 4 cycles in induction period and additional 12 cycles in maintenance period	Rituxan n=128 Participants Rituxan, 375mg/m2, IV, 4 cycles in induction period, Rituxan for the first 6 cycles and CT-P10 for the last 6 cycles in maintenance period.
Secondary Efficacy Endpoint - Time-to Progression (TTP) 12 months	0.94 Proportion of Participants Interval 0.88 to 0.97	0.89 Proportion of Participants Interval 0.83 to 0.94
Secondary Efficacy Endpoint - Time-to Progression (TTP) 24 months	0.89 Proportion of Participants Interval 0.82 to 0.94	0.84 Proportion of Participants Interval 0.76 to 0.89
Secondary Efficacy Endpoint - Time-to Progression (TTP) 36 months	0.82 Proportion of Participants Interval 0.72 to 0.88	0.68 Proportion of Participants Interval 0.54 to 0.79

Adverse Events

CT-P10

Serious events: 14 serious events

Other events: 93 other events

Deaths: 3 deaths

Rituxan

Serious events: 14 serious events

Other events: 86 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Sung Hyun Kim

CELLTRION, Inc.

Phone: +82-32-850-5000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A confidentiality and non-disclosure agreement (CDA) was executed between Celltrion, Inc. and some PIs who have participated in publications funded by the sponsor for academic purposes for a period that is more than 180 days from the time submitted to the sponsor for review.
Publication restrictions are in place

Restriction type: OTHER

Measure	CT-P10 n=130 participants at risk CT-P10 375mg/m2, IV, 4 cycles in induction period and additional 12 cycles in maintenance period	Rituxan n=128 participants at risk Rituxan, 375mg/m2, IV, 4 cycles in induction period, Rituxan for the first 6 cycles and CT-P10 for the last 6 cycles in maintenance period.
Cardiac disorders Angina unstable	0.00% 0/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.78% 1/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Cardiac disorders Atrial fibrillation	0.00% 0/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.78% 1/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Cardiac disorders Bradycardia	0.77% 1/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.00% 0/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Cardiac disorders Myocardial infarction	0.77% 1/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.00% 0/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Endocrine disorders Hyperparathyroidism	0.00% 0/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.78% 1/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Gastrointestinal disorders Constipation	0.77% 1/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.00% 0/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Gastrointestinal disorders Crohn's disease	0.77% 1/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.00% 0/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Gastrointestinal disorders Gastric haemorrhage	0.77% 1/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.00% 0/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Gastrointestinal disorders Gastritis	0.77% 1/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.00% 0/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Gastrointestinal disorders Intestinal polyp	0.00% 0/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.78% 1/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Gastrointestinal disorders Pancreatitis	0.00% 0/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.78% 1/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Gastrointestinal disorders Peptic ulcer perforation	0.00% 0/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.78% 1/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
General disorders Chest discomfort	0.77% 1/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.00% 0/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Infections and infestations Localised infection	0.00% 0/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.78% 1/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Infections and infestations Pneumonia	0.00% 0/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	1.6% 2/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Infections and infestations Urinary tract infection	0.00% 0/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.78% 1/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.77% 1/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.00% 0/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.77% 1/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.00% 0/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Nasal neoplasm benign	0.00% 0/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.78% 1/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of lung	0.77% 1/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.00% 0/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Nervous system disorders Cerebral infarction	0.77% 1/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.00% 0/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.77% 1/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.00% 0/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Renal and urinary disorders Acute kidney injury	0.00% 0/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.78% 1/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Reproductive system and breast disorders Genital prolapse	0.00% 0/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.78% 1/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.78% 1/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.77% 1/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.00% 0/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.77% 1/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.00% 0/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Surgical and medical procedures Gastrointestinal surgery	0.77% 1/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	0.00% 0/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.

Measure	CT-P10 n=130 participants at risk CT-P10 375mg/m2, IV, 4 cycles in induction period and additional 12 cycles in maintenance period	Rituxan n=128 participants at risk Rituxan, 375mg/m2, IV, 4 cycles in induction period, Rituxan for the first 6 cycles and CT-P10 for the last 6 cycles in maintenance period.
Blood and lymphatic system disorders Neutropenia	7.7% 10/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	5.5% 7/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Gastrointestinal disorders Abdominal pain	4.6% 6/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	5.5% 7/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Gastrointestinal disorders Diarrhoea	6.9% 9/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	8.6% 11/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Gastrointestinal disorders Nausea	5.4% 7/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	8.6% 11/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
General disorders Fatigue	7.7% 10/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	10.2% 13/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Infections and infestations Herpes virus infection	5.4% 7/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	3.9% 5/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Infections and infestations Influenza	2.3% 3/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	6.2% 8/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Infections and infestations Lower respiratory tract infection	4.6% 6/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	8.6% 11/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Infections and infestations Upper respiratory tract infection	23.8% 31/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	22.7% 29/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Infections and infestations Urinary tract infection	6.9% 9/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	10.2% 13/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Injury, poisoning and procedural complications Infusion related reaction	32.3% 42/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	30.5% 39/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Investigations Alanine aminotransferase increased	5.4% 7/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	2.3% 3/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Musculoskeletal and connective tissue disorders Back pain	6.2% 8/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	3.9% 5/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Nervous system disorders Headache	4.6% 6/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	5.5% 7/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Respiratory, thoracic and mediastinal disorders Cough	6.9% 9/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	9.4% 12/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.
Vascular disorders Hypertension	7.7% 10/130 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.	4.7% 6/128 • Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from the last dose of the study drug, regardless of the relationship to the study drug. data from the overall study period (median follow-up of 29.2 months) are presented.