Trial Outcomes & Findings for A Safety and Efficacy Study of BCD-022 With Paclitaxel Compared to Herceptin With Paclitaxel in HER2+ Metastatic Breast Cancer Patients (NCT NCT01764022)

Last Updated: 2018-11-29

Results Overview

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. The response was assessed at the screening, after 3 therapy cycles and after 6 therapy cycles. If CT after 3 or 6 therapy cycles revealed the complete or partial response, a confirmatory CT scan was performed 4 weeks later. The best response during the study was assessed.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

225 participants

Primary outcome timeframe

Day 127

Results posted on

2018-11-29

Participant Flow

In BCD-022 group 2 patients were exluded from any analysis due to: * Death prior to the first drug administration * Informed consent withdrawal prior to the first drug administration

Participant milestones

Participant milestones
Measure	BCD-022 (CJSC BIOCAD) BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland) In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
Overall Study STARTED	115	110
Overall Study Received at Least 1 Dose of Study Drug	113	110
Overall Study COMPLETED	107	96
Overall Study NOT COMPLETED	8	14

Reasons for withdrawal

Reasons for withdrawal
Measure	BCD-022 (CJSC BIOCAD) BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland) In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
Overall Study Death	3	5
Overall Study Withdrawal by Subject	2	6
Overall Study Lack of Efficacy	0	1
Overall Study Physician Decision	0	2
Overall Study Lost to Follow-up	2	0
Overall Study Protocol Violation	1	0

Baseline Characteristics

A Safety and Efficacy Study of BCD-022 With Paclitaxel Compared to Herceptin With Paclitaxel in HER2+ Metastatic Breast Cancer Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BCD-022 (CJSC BIOCAD) n=115 Participants BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland) n=110 Participants In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	Total n=225 Participants Total of all reporting groups
Age, Continuous	50.687 years STANDARD_DEVIATION 10.948 • n=5 Participants	50.573 years STANDARD_DEVIATION 9.877 • n=7 Participants	50.63 years STANDARD_DEVIATION 10.415 • n=5 Participants
Sex: Female, Male Female	115 Participants n=5 Participants	110 Participants n=7 Participants	225 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
HER2 Expression HER2 +++	100 Participants n=5 Participants	97 Participants n=7 Participants	197 Participants n=5 Participants
HER2 Expression HER2 ++	14 Participants n=5 Participants	13 Participants n=7 Participants	27 Participants n=5 Participants
HER2 Expression Unknown	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Histologic type of cancer Ductal	36 Participants n=5 Participants	33 Participants n=7 Participants	69 Participants n=5 Participants
Histologic type of cancer Medullar	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Histologic type of cancer Lobular	23 Participants n=5 Participants	18 Participants n=7 Participants	41 Participants n=5 Participants
Histologic type of cancer Tubular	35 Participants n=5 Participants	37 Participants n=7 Participants	72 Participants n=5 Participants
Histologic type of cancer Mucinouse	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Histologic type of cancer Micropapillary	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Histologic type of cancer Unknown histilogic type	14 Participants n=5 Participants	13 Participants n=7 Participants	27 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 127

Population: The population for efficacy analysis included patients who received at least one injection of study drug and had evaluable results of treatment.

Outcome measures

Outcome measures
Measure	BCD-022 (CJSC BIOCAD) n=113 Participants BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland) n=110 Participants In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
Overall Response Rate	56 Participants	48 Participants

PRIMARY outcome

Timeframe: up to Day 22, after the first trastuzumab administration (time points for blood samples: 0 h 1.5 h, 3 h, 4.5 h, 6 h, 24 h, 96 h, 168 h, 336 h and 504 h)

Population: Patients who received one dose of study drug and after 504 hours after the injection had missed \<= 1 blood sample collection to analyse pharmacokinetics.

Primary outcome measure for pharmacokinetics (PK) substudy. AUC(0-504) of trastuzumab in HER2(+) mBC patients after first administration of BCD-022 with paclitaxel or Herceptin® with paclitaxel.

Outcome measures

Outcome measures
Measure	BCD-022 (CJSC BIOCAD) n=107 Participants BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland) n=104 Participants In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
Area Under the Curve After the First Test Drug Administration	28969372.5 (ng/ml)*hour Interval 20165337.0 to 36096712.5	28796527.9 (ng/ml)*hour Interval 20430685.5 to 36232918.5

SECONDARY outcome

Timeframe: Day 127

Population: The population for efficacy analysis included patients who received at least one injection of study drug and had evaluable results of treatment.

Outcome measures

Outcome measures
Measure	BCD-022 (CJSC BIOCAD) n=113 Participants BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland) n=110 Participants In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
Complete Response Rate	4 Participants	2 Participants

SECONDARY outcome

Timeframe: Day 127

Population: The population for efficacy analysis included patients who received at least one injection of study drug and had evaluable results of treatment.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. The response was assessed at the screening, after 3 therapy cycles and after 6 therapy cycles. If CT after 3 or 6 therapy cycles revealed the complete or partial response, a confirmatory CT scan was performed 4 weeks later. The best response during the study was assessed.

Outcome measures

Outcome measures
Measure	BCD-022 (CJSC BIOCAD) n=113 Participants BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland) n=110 Participants In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
Partial Response Rate	52 Participants	46 Participants

SECONDARY outcome

Timeframe: Day 127

Population: The population for efficacy analysis included patients who received at least one injection of study drug and had evaluable results of treatment.

Outcome measures

Outcome measures
Measure	BCD-022 (CJSC BIOCAD) n=113 Participants BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland) n=110 Participants In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
Stabilization Rate	28 Participants	21 Participants

SECONDARY outcome

Timeframe: Day 127

Population: The population for efficacy analysis included patients who received at least one injection of study drug and had evaluable results of treatment.

Outcome measures

Outcome measures
Measure	BCD-022 (CJSC BIOCAD) n=113 Participants BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland) n=110 Participants In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
Progression Rate	25 Participants	28 Participants

SECONDARY outcome

Timeframe: Day 127

Population: Patients who received at least one injection of study drug.

Secondary outcome measure for safety evaluation

Outcome measures

Outcome measures
Measure	BCD-022 (CJSC BIOCAD) n=113 Participants BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland) n=110 Participants In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
Treatment Postponed Due to AE/SAE	4 participants	5 participants

SECONDARY outcome

Timeframe: Day 127

Population: Patients who received at least one injection of study drug.

Secondary outcome measure for safety evaluation

Outcome measures

Outcome measures
Measure	BCD-022 (CJSC BIOCAD) n=113 Participants BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland) n=110 Participants In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
Treatment Discontinuation Due to AE/SAE	0 participants	1 participants

SECONDARY outcome

Timeframe: Day 1 (before the drug administration), Day 14, 64, 127 and 154

Population: Patients who received at least one injection of study drug

Secondary outcome measure for immunogenicity assessment. Patient was suggested as NAB-positive if neutralizing anti-trastuzumab antibodies were detected at any of the specified timepoints. Total number of NAB-positive patients in each are presented.

Outcome measures

Outcome measures
Measure	BCD-022 (CJSC BIOCAD) n=113 Participants BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland) n=110 Participants In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
Occurrence of Neutralizing Anti-trastuzumab Antibodies	3 participants	4 participants

SECONDARY outcome

Timeframe: Up to Day 22

Population: Patients who received one dose of study drug and after 504 hours after the injection had missed \<= 1 blood sample collection to analyse pharmacokinetics.

Secondary outcome measure for PK substudy. Peak serum concentration of trastuzumab after single administration of BCD-022 + paclitaxel or Herceptin® + paclitaxel

Outcome measures

Outcome measures
Measure	BCD-022 (CJSC BIOCAD) n=107 Participants BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland) n=104 Participants In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
Cmax After the First Test Drug Administration	218720.0 ng/ml Interval 178270.0 to 264700.0	216710.0 ng/ml Interval 186740.0 to 269780.0

SECONDARY outcome

Timeframe: Up to Day 22

Population: Patients who received one dose of study drug and after 504 hours after the injection had missed \<= 1 blood sample collection to analyse pharmacokinetics.

Secondary outcome measure for PK substudy. Time to reach peak serum concentration of trastuzumab after the first administration of BCD-022 + paclitaxel or Herceptin® + paclitaxel

Outcome measures

Outcome measures
Measure	BCD-022 (CJSC BIOCAD) n=107 Participants BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland) n=104 Participants In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
Tmax After the First Test Drug Administration	160.6 hours Interval 103.2 to 207.6	162.1 hours Interval 101.9 to 201.6

SECONDARY outcome

Timeframe: Up to Day 22

Population: Patients who received one dose of study drug and after 504 hours after the injection had missed \<= 1 blood sample collection to analyse pharmacokinetics.

Secondary outcome measure for PK substudy. Half-life period of trastuzumab after the first administration of BCD-022 + paclitaxel or Herceptin® + paclitaxel.

Outcome measures

Outcome measures
Measure	BCD-022 (CJSC BIOCAD) n=104 Participants BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland) n=107 Participants In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
T1/2 After the First Test Drug Administration	162.1 hours Interval 101.9 to 201.6	160.6 hours Interval 103.2 to 207.6

SECONDARY outcome

Timeframe: Up to Day 127

Population: Patients who received six dose of study drug and had missed \<= 1 blood sample collection to analyse pharmacokinetics.

Secondary outcome measure for PK substudy. Peak serum concentration of trastuzumab after the sixth administration of BCD-022 + paclitaxel or Herceptin® + paclitaxel.

Outcome measures

Outcome measures
Measure	BCD-022 (CJSC BIOCAD) n=36 Participants BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland) n=33 Participants In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
Cmax After the Sixth Test Drug Administration	168735.0 ng/ml Interval 148810.0 to 204870.0	169220.0 ng/ml Interval 150140.0 to 179230.0

SECONDARY outcome

Timeframe: Up to Day 127

Population: Patients who received six dose of study drug and had missed \<= 1 blood sample collection to analyse pharmacokinetics.

Secondary outcome measure for PK substudy. Time to reach peak serum concentration of trastuzumab after the sixth administration of BCD-022 + paclitaxel or Herceptin® + paclitaxel

Outcome measures

Outcome measures
Measure	BCD-022 (CJSC BIOCAD) n=36 Participants BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland) n=33 Participants In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
Tmax After the Sixth Test Drug Administration	185.8 hour Interval 146.3 to 237.1	192.9 hour Interval 137.9 to 237.1

Adverse Events

BCD-022 (CJSC BIOCAD)

Serious events: 8 serious events

Other events: 106 other events

Deaths: 3 deaths

Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland)

Serious events: 13 serious events

Other events: 104 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Mariia Shustova

BIOCAD

Phone: +7812380 49 33

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	BCD-022 (CJSC BIOCAD) n=113 participants at risk BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland) n=110 participants at risk In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
Respiratory, thoracic and mediastinal disorders Pneumonia	0.88% 1/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	0.00% 0/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Gastrointestinal disorders Gastrointestinal hemorrhage	0.88% 1/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	0.00% 0/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Disease progression	0.88% 1/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	1.8% 2/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
General disorders Death for unknown reason	0.88% 1/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	0.91% 1/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	0.91% 1/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Cardiac disorders Paroxism of atrial fibrillation	0.00% 0/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	1.8% 2/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Cardiac disorders Ventricular extrasystolone RYAN-1	0.00% 0/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	0.91% 1/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Blood and lymphatic system disorders Anemia with trombocytopenia	0.00% 0/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	0.91% 1/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
General disorders Diarrhea with vomiting and weakness	0.00% 0/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	0.91% 1/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Infections and infestations Neutropenic sepsis	0.88% 1/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	0.00% 0/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Infections and infestations Pneumonitis with Septicemia	0.00% 0/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	0.91% 1/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Respiratory, thoracic and mediastinal disorders Aspiration pneumonia	0.00% 0/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	0.91% 1/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Respiratory, thoracic and mediastinal disorders Chest pain	0.88% 1/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	0.00% 0/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Blood and lymphatic system disorders Neutropenia	0.88% 1/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	0.91% 1/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Reproductive system and breast disorders Сervicitis	0.88% 1/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	0.00% 0/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Vascular disorders Hepatic veins compression	0.00% 0/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	0.91% 1/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
General disorders Non-Neutropenic Fever	0.00% 0/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	1.8% 2/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Respiratory, thoracic and mediastinal disorders Bronchitis	0.00% 0/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	0.91% 1/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Respiratory, thoracic and mediastinal disorders Bronchopneumonia	0.00% 0/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	0.91% 1/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).

Measure	BCD-022 (CJSC BIOCAD) n=113 participants at risk BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland) n=110 participants at risk In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
Blood and lymphatic system disorders Leucopenia	56.6% 64/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	49.1% 54/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Blood and lymphatic system disorders Leucocytosis	21.2% 24/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	31.8% 35/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Blood and lymphatic system disorders Neutropenia	58.4% 66/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	50.9% 56/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Blood and lymphatic system disorders Anemia	66.4% 75/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	66.4% 73/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Blood and lymphatic system disorders Trombocytopenia	16.8% 19/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	19.1% 21/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Blood and lymphatic system disorders Elevated absolute neutrophil count	23.0% 26/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	26.4% 29/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Blood and lymphatic system disorders Elevated hemoglobin	5.3% 6/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	10.0% 11/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Blood and lymphatic system disorders Lymphopenia	46.9% 53/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	36.4% 40/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Blood and lymphatic system disorders Lymphocytosis	12.4% 14/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	15.5% 17/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Blood and lymphatic system disorders Erythropenia	23.0% 26/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	22.7% 25/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Blood and lymphatic system disorders Erythrocytosis	10.6% 12/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	12.7% 14/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Blood and lymphatic system disorders Trombocytosis	23.9% 27/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	20.9% 23/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Metabolism and nutrition disorders Hyperglycemia	34.5% 39/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	42.7% 47/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Metabolism and nutrition disorders Hyperuricemia	16.8% 19/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	21.8% 24/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Hepatobiliary disorders Elevated alkaline phosphotase	24.8% 28/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	24.5% 27/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Hepatobiliary disorders Elevated AST	25.7% 29/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	23.6% 26/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Hepatobiliary disorders Elevated ALT	21.2% 24/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	22.7% 25/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Skin and subcutaneous tissue disorders Alopecia	23.0% 26/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	23.6% 26/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Musculoskeletal and connective tissue disorders Arthralgia	9.7% 11/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	10.0% 11/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Musculoskeletal and connective tissue disorders Myalgia	13.3% 15/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	9.1% 10/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Gastrointestinal disorders Nausea	6.2% 7/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	4.5% 5/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Gastrointestinal disorders Vomiting	5.3% 6/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	4.5% 5/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Respiratory, thoracic and mediastinal disorders Bradypnoea	13.3% 15/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	11.8% 13/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Reproductive system and breast disorders Tachypnoea	8.0% 9/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	7.3% 8/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Nervous system disorders Neuropathy	11.5% 13/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	8.2% 9/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Renal and urinary disorders Elevated urea	9.7% 11/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	11.8% 13/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Renal and urinary disorders Elevated creatinine	14.2% 16/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	12.7% 14/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Vascular disorders Arterial hypertension	11.5% 13/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	10.0% 11/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Cardiac disorders Tachycardia	19.5% 22/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	10.9% 12/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
General disorders Fever	14.2% 16/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	12.7% 14/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
General disorders Generalized weakness	23.0% 26/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	22.7% 25/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).
Investigations Elevated lactate degydrohenase	30.1% 34/113 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).	29.1% 32/110 • up to 154 days Population for safety analysis included patients who received at least one injection of study drug (n=223).