Bioequivalence Study Bevacizumab Biosimilar (BEVZ92) Vers... | NCT02069704

NCT02069704

ID	Type	Description	Link
BEVZ92-A-01-13	Registry Identifier	BEVZ92-A-01-13

Status Module

Sponsor/Collaborators Module

Name	Class
Laboratorio Elea Phoenix S.A.	INDUSTRY
Libbs Farmacêutica LTDA	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Bevacizumab biosimilar (BEVZ92)	Experimental	Bevacizumab 25 mg/mL (strength: 100 mg/4 mL).	Drug: Bevacizumab biosimilar (BEVZ92)
Avastin® (bevacizumab, ref. product)	Active Comparator	Bevacizumab 25mg/ml (strength: 100mg/4ml)	Drug: Avastin® (bevacizumab, reference product)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Bevacizumab biosimilar (BEVZ92)	Drug	Active ingredient Bevacizumab 25 mg/mL (strength = 100 mg/4 mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri). FOLFIRI = Folinic Acid + Fluorouracil + Irinotecan FOLFOX = Folinic Acid + Fluorouracil + Oxaliplatin Treatment will continue until disease progression, unacceptable toxicity, patient withdraws consent or death (whichever occurs first). *The first infusion will be given over 90 minutes. If it is well tolerated, the second infusion can be given over 60 minutes. If it is well tolerated, subsequent infusions can be given over 30 minutes. The FOLFOX (any) or FOLFIRI regimen will be chosen as per investigator's criteria based on the hospital standard of care.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Area Under the Concentration-versus-time Curve (AUC) at Cycle 1 (AUC0-336h) of BEVZ92 and Avastin®	To compare the pharmacokinetic (PK) profile of BEVZ92 and Avastin®, both administered in combination with FOLFOX (any) or FOLFIRI, by means of comparing the truncated AUC calculated from start of the first infusion until start of the second infusion (i.e. at Cycle 1; AUC0-336h) For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) of the ratio of a log-transformed exposure measure (AUC) falls completely within the range 80-125%.	AUC0-336 hrs: 0 to 336 hours after start of the first infusion
AUC at Steady State (AUCss) of BEVZ92 and Avastin®	To compare the PK profile of BEVZ92 and Avastin®, both administered in combination with FOLFOX (any) or FOLFIRI, by means of comparing the truncated area under the concentration-versus-time curve calculated over a dosage interval at steady state (i.e. at Cycle 7; AUCss). For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% CI of the ratio of a log-transformed exposure measure (AUC) falls completely within the range 80-125%.	AUCss: 0 to 336 hours after the administration of Cycle 7 infusion (Week 13).

Secondary Outcomes

Measure	Description	Time Frame
Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Reported With BEVZ92 and Avastin®	Compare the safety profile by means of the frequency and severity of TEAEs and SAEs reported in each treatment arm.	From first study dose and up to 30 days after the end of study treatment for each patient, for an average of 11 months

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patient must not have had prior chemotherapy for advanced or metastatic disease. Patients could have received adjuvant chemotherapy or adjuvant chemo-radiotherapy.
Patient with mCRC for whom bio-chemotherapy is indicated.
Patients must have at least one measurable non-irradiated site of disease according to RECIST (version 1.1) criteria. If the patient has had previous irradiation of the marker lesion(s), there must be evidence of progression since the radiation.
Minimum of 4 weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
Adequate bone marrow function
Adequate liver function defined within specific parameters
Adequate renal function defined within specific parameters
Adequate coagulation parameters defined within specific parameters
Negative pregnancy test for females of a childbearing potential.
Use of an effective form of contraception during the study (for subjects of childbearing potential and their partners).
Life expectation ≥ 3 months

Exclusion Criteria:

Prior treatment for advanced or metastatic colorectal cancer.
Prior treatment with an anti-angiogenesis agent, in either the neoadjuvant or adjuvant setting.
Concurrent use of investigational anti-neoplastic agents (including up to 4 weeks prior to enrolment).
History of any other malignancy unless the malignancy is in complete remission and the patient has been off all therapy for that malignancy for at least 5 years.
Chronic treatment with systemic steroids or other immunosuppressive agents; topical or inhaled corticosteroids are allowed.
Scheduled immunization with attenuated live vaccines during study period or within 1 week prior to study entry.
Uncontrolled brain or lepto-meningeal metastases, including patients who continue to require glucocorticoids for brain or lepto-meningeal metastases.
Patients with active bleeding or history of bleeding diathesis on oral anti-vitamin K medication (except low dose coumadin) within the past 6 month prior to randomization or coagulopathy.
Patients with history of cerebral vascular accident, transient ischemic attack, or subarachnoid haemorrhage within the past 6 month prior to randomization.
Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
Patients with serious non-healing wound, ulcer, bone fracture, or with a major surgical procedure, or significant traumatic injury within 4 weeks prior to randomization
Patients with clinical symptoms or signs of gastrointestinal obstruction that require parenteral hydration and/or nutrition.
Patients with history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months prior to randomization.
Patients with history of hypersensitivity to any of the study drugs or ingredients.

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
Hospital de Gastroenterologia "Dr. Carlos Bonorino Udaondo"		Buenos Aires			Argentina
Instituto Oncológico de Rosario

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
30262136	Derived	Romera A, Peredpaya S, Shparyk Y, Bondarenko I, Mendonca Bariani G, Abdalla KC, Roca E, Franke F, Melo Cruz F, Ramesh A, Ostwal V, Shah P, Rahuman SA, Paravisini A, Huerga C, Del Campo Garcia A, Millan S. Bevacizumab biosimilar BEVZ92 versus reference bevacizumab in combination with FOLFOX or FOLFIRI as first-line treatment for metastatic colorectal cancer: a multicentre, open-label, randomised controlled trial. Lancet Gastroenterol Hepatol. 2018 Dec;3(12):845-855. doi: 10.1016/S2468-1253(18)30269-3. Epub 2018 Sep 24.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Bevacizumab Biosimilar (BEVZ92)	Bevacizumab biosimilar (BEVZ92): Bevacizumab biosimilar (BEVZ92), Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).
FG001	Avastin® (Bevacizumab, Ref. Product)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

FG00069 subjectsTwo patients were randomized but they did not received study treatment

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Bevacizumab Biosimilar (BEVZ92)	Bevacizumab biosimilar (BEVZ92): Bevacizumab biosimilar (BEVZ92), Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).
BG001	Avastin® (Bevacizumab, Ref. Product)	Avastin® (bevacizumab, reference product): Avastin® (bevacizumab, reference product). Active ingredient: Bevacizumab 25 mg/mL (strength: 100 mg/4 mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to administration of chemotherapy (Folfox any or Folfiri).
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG00016500000± 30.7 OG00116600000± 31.8

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Based on previously published PK data for reference bevacizumab in metastatic colorectal cancer, we assumed a conservative inter-participant coefficient of variation for AUC of around 35%. A sample size of 51 patients in each treatment arm could show bioequivalence with a nominal power of 90% and an α of 0·05, if the 90% CIs for the ratio of BEVZ92 to reference bevacizumab of the geometric means for AUC0-336h and AUCss were within the acceptance interval of 80%-125%.					ratio BEVZ92 to Avastin	99.4			2-Sided	90	90.5	109.0			For the ratio: BEVZ92 represents the numerator and reference bevacizumab the denominator

Primary

AUC at Steady State (AUCss) of BEVZ92 and Avastin®

To compare the PK profile of BEVZ92 and Avastin®, both administered in combination with FOLFOX (any) or FOLFIRI, by means of comparing the truncated area under the concentration-versus-time curve calculated over a dosage interval at steady state (i.e. at Cycle 7; AUCss).

For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% CI of the ratio of a log-transformed exposure measure (AUC) falls completely within the range 80-125%.

In the Avastin arm there were 3 missing samples at the timepoint required for the specific PK parameters within Cycle 7.

Posted

Geometric Least Squares Mean

Geometric Coefficient of Variation

ng.h/mL

AUCss: 0 to 336 hours after the administration of Cycle 7 infusion (Week 13).

ID	Title	Description
OG000	Bevacizumab Biosimilar (BEVZ92)	Bevacizumab proposed biosimilar (BEVZ92): Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).
OG001	Avastin® (Bevacizumab, Ref. Product).	Bevacizumab reference product: Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Secondary

Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Reported With BEVZ92 and Avastin®

Compare the safety profile by means of the frequency and severity of TEAEs and SAEs reported in each treatment arm.

All patients receiving at least one dose of study medication.

Posted

Number

participants

From first study dose and up to 30 days after the end of study treatment for each patient, for an average of 11 months

ID	Title	Description
OG000	Bevacizumab Biosimilar (BEVZ92)	Bevacizumab 25 mg/mL (strength: 100 mg/4 mL). Bevacizumab biosimilar (BEVZ92): Bevacizumab biosimilar (BEVZ92), Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).
OG001	Avastin® (Bevacizumab, Ref. Product)	Bevacizumab 25mg/ml (strength: 100mg/4ml) Avastin® (bevacizumab, reference product): Avastin® (bevacizumab, reference product). Active ingredient: Bevacizumab 25 mg/mL (strength: 100 mg/4 mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to administration of chemotherapy (Folfox any or Folfiri).

Units	Counts

Secondary

Anti-Drug Antibody (ADA) of BEVZ92 and Avastin®

Immunogenicity profile by means of measurement of ADA developed de novo (seroconversion) after cycle 5, cycle 8, and 12 months after first drug administration (pre-dose).

All patients receiving at least one dose of study medication.

Posted

Number

participants

At baseline, and on Day 1 (pre-dose) of Cycles: 1, 5 and 8, and 12 months after first drug administration

ID	Title	Description
OG000	Bevacizumab Biosimilar (BEVZ92)	Bevacizumab 25 mg/mL (strength: 100 mg/4 mL). Bevacizumab biosimilar (BEVZ92): Bevacizumab biosimilar (BEVZ92), Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).
OG001	Avastin® (Bevacizumab, Ref. Product)	Bevacizumab 25mg/ml (strength: 100mg/4ml) Avastin® (bevacizumab, reference product): Avastin® (bevacizumab, reference product). Active ingredient: Bevacizumab 25 mg/mL (strength: 100 mg/4 mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to administration of chemotherapy (Folfox any or Folfiri).

Units	Counts

Secondary

Objective Response Rate (ORR) of BEVZ92 and Avastin®

To compare efficacy in terms of ORR between arms. Clinical and radiological tumor assessments were performed according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 using computed tomography (CT) or magnetic resonance imaging (MRI) scans.

Objective response (OR) is defined as a best overall response of partial response (PR) or complete response (CR) as defined by RECIST v1.1. All participants who did not meet the criteria for CR or PR by the end of the study were considered non-responders.

Intent-to-treat population

Posted

Count of Participants

Participants

Every four weeks. Up to 48 weeks

ID	Title	Description
OG000	Bevacizumab Biosimilar (BEVZ92)	Bevacizumab 25 mg/mL (strength: 100 mg/4 mL). Bevacizumab biosimilar (BEVZ92): Bevacizumab biosimilar (BEVZ92), Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).
OG001	Avastin® (Bevacizumab, Ref. Product)	Bevacizumab 25mg/ml (strength: 100mg/4ml) Avastin® (bevacizumab, reference product): Avastin® (bevacizumab, reference product). Active ingredient: Bevacizumab 25 mg/mL (strength: 100 mg/4 mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to administration of chemotherapy (Folfox any or Folfiri).

Secondary

Cmax,sd of BEVZ92 and Avastin®

Secondary PK endpoints included the Cmax calculated at Cycle 1 (Cmax,sd )

Overall number of participants Analyzed equals to number of subjects who contributed to summary statistics.

Posted

Geometric Least Squares Mean

Geometric Coefficient of Variation

ng/mL

Cmax, sd: 0 to 336 hours after start of the first infusion.

ID	Title	Description
OG000	Bevacizumab Biosimilar (BEVZ92)	Bevacizumab proposed biosimilar (BEVZ92): Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).
OG001	Avastin® (Bevacizumab, Ref. Product).	Bevacizumab reference product: Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Units	Counts
Participants	OG000

Secondary

Progression-free Survival (PFS) of BEVZ92 and Avastin®

Compare PFS between the randomized treatment arms. Progression-free survival (PFS) was defined as the time from the randomization date to the date of disease progression using RECIST v1.1, or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions plus 5 mm absolute increase, and/or unequivocal progression of known non-target lesion, and/or the appearance of new lesions".

Intent-to-treat population

Posted

Median

95% Confidence Interval

months

From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 weeks.

ID	Title	Description
OG000	Bevacizumab Biosimilar (BEVZ92)	Bevacizumab proposed biosimilar (BEVZ92): Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).
OG001	Avastin® (Bevacizumab, Ref. Product)	Bevacizumab reference product: Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Secondary

Cmax,ss of BEVZ92 and Avastin®

Secondary PK endpoints included the Cmax calculated at Cycle 7 (Cmax, ss )

In the Avastin arm there were 3 missing samples at the timepoint required for the specific PK parameter within Cycle 7.

Posted

Geometric Least Squares Mean

Geometric Coefficient of Variation

ng/mL

Cmax, ss: 0 to 336 hours post-dose after the administration of Cycle 7 infusion (Week 13)

ID	Title	Description
OG000	Bevacizumab Biosimilar (BEVZ92)	Bevacizumab proposed biosimilar (BEVZ92): Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).
OG001	Avastin® (Bevacizumab, Ref. Product).	Bevacizumab reference product: Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Units	Counts
Participants

Secondary

Ctrough,sd of BEVZ92 and Avastin®

Secondary PK endpoints included the Ctrough calculated at Cycle 1 (Ctrough,sd )

In the Avastin arm there was 1 missing samples at the timepoint required for the specific PK parameter within Cycle 1.

Posted

Geometric Least Squares Mean

Geometric Coefficient of Variation

ng/mL

Ctrough, sd: 0 to 336 hours after start of the first infusion.

ID	Title	Description
OG000	Bevacizumab Biosimilar (BEVZ92)	Bevacizumab proposed biosimilar (BEVZ92): Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).
OG001	Avastin® (Bevacizumab, Ref. Product).	Bevacizumab reference product: Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Units	Counts
Participants	OG000

Secondary

Ctrough,ss of BEVZ92 and Avastin®

Secondary PK endpoints included the Ctrough calculated at Cycle 7 (Ctrough,ss)

There were 4 missing samples (1 in the BEVZ92 and 3 in the Avastin arm) at the timepoint required for the specific PK parameter within Cycle 7.

Posted

Geometric Least Squares Mean

Geometric Coefficient of Variation

ng/mL

Ctrough, ss: 0 to 336 hours after the administration of the Cycle 7 infusion.

ID	Title	Description
OG000	Bevacizumab Biosimilar (BEVZ92)	Bevacizumab proposed biosimilar (BEVZ92): Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).
OG001	Avastin® (Bevacizumab, Ref. Product).	Bevacizumab reference product: Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Units	Counts
Participants

Secondary

Elimination Half-life (t1/2) of BEVZ92 and Avastin®

Secondary PK endpoints included the t1/2 calculated at Cycle 7

In the Avastin arm there were several missing samples at the timepoint required for the specific PK parameter

Posted

Geometric Least Squares Mean

Geometric Coefficient of Variation

t1/2: 0 to 336 hours after the administration of the Cycle 7 infusion.

ID	Title	Description
OG000	Bevacizumab Biosimilar (BEVZ92)	Bevacizumab proposed biosimilar (BEVZ92): Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).
OG001	Avastin® (Bevacizumab, Ref. Product).	Bevacizumab reference product: Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Units	Counts
Participants	OG000

Secondary

Elimination Rate Constant (Kel) of BEVZ92 and Avastin®

Secondary PK endpoints included the Kel calculated at Cycle 7 (Ctrough,ss)

Overall number of participants Analyzed equals to number of subjects who contributed to summary statistics.

Posted

Geometric Least Squares Mean

Geometric Coefficient of Variation

l/h

Kel: 0 to 336 hours after the administration of the Cycle 7 infusion.

ID	Title	Description
OG000	Bevacizumab Biosimilar (BEVZ92)	Bevacizumab proposed biosimilar (BEVZ92): Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).
OG001	Avastin® (Bevacizumab, Ref. Product).	Bevacizumab reference product: Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Units	Counts
Participants	OG000

Secondary

Volume of Distribution (Vd) of BEVZ92 and Avastin®

Secondary PK endpoints included the Vd calculated at Cycle 7

In the Avastin arm there were several missing samples at the timepoint required for the specific PK parameter

Posted

Geometric Least Squares Mean

Geometric Coefficient of Variation

Vd: 0 to 336 hours after the administration of the Cycle 7 infusion.

ID	Title	Description
OG000	Bevacizumab Biosimilar (BEVZ92)	Bevacizumab proposed biosimilar (BEVZ92): Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).
OG001	Avastin® (Bevacizumab, Ref. Product).	Bevacizumab reference product: Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Bevacizumab Biosimilar (BEVZ92)	Bevacizumab biosimilar (BEVZ92): Bevacizumab biosimilar (BEVZ92), Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).	11	69	19	69	66	69
EG001	Avastin® (Bevacizumab, Ref. Product)	Avastin® (bevacizumab, reference product): Avastin® (bevacizumab, reference product). Active ingredient: Bevacizumab 25 mg/mL (strength: 100 mg/4 mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to administration of chemotherapy (Folfox any or Folfiri).	7	71	21	71	71	71

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Diarrhea	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0015 events4 affected71 at risk
Constipation	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0010 events0 affected71 at risk
Enteritis	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0000 events0 affected69 at risk EG0011 events1 affected71 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0006 events5 affected69 at risk EG0010 events0 affected71 at risk
Ileus paralytic	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0000 events0 affected69 at risk EG0011 events1 affected71 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0000 events0 affected69 at risk EG0011 events1 affected71 at risk
Lower Gastrointestinal hemorrhage	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0010 events0 affected71 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0000 events0 affected69 at risk EG0011 events1 affected71 at risk
Subileus	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0000 events0 affected69 at risk EG0011 events1 affected71 at risk
Bronchopneumonia	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0010 events0 affected71 at risk
Sepsis	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0013 events3 affected71 at risk
Urinary tract infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0012 events2 affected71 at risk
Catheter site abscess	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0000 events0 affected69 at risk EG0011 events1 affected71 at risk
Oral candidiasis	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0011 events1 affected71 at risk
Peritonitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0000 events0 affected69 at risk EG0011 events1 affected71 at risk
Septic shock	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0011 events1 affected71 at risk
Diarrhea infectious	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0010 events0 affected71 at risk
Pelvic Abscess	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0000 events0 affected69 at risk EG0011 events1 affected71 at risk
Pneumonia	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0011 events1 affected71 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0016 events4 affected71 at risk
Anemia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0014 events3 affected71 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment		EG0000 events0 affected69 at risk EG0012 events2 affected71 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0010 events0 affected71 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0012 events1 affected71 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment		EG0000 events0 affected69 at risk EG0011 events1 affected71 at risk
Hypernatremia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0011 events1 affected71 at risk
Hypoalbuminemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment		EG0000 events0 affected69 at risk EG0011 events1 affected71 at risk
Hypokalemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment		EG0000 events0 affected69 at risk EG0013 events1 affected71 at risk
Monoparesis	Nervous system disorders	MedDRA (16.0)	Systematic Assessment		EG0000 events0 affected69 at risk EG0011 events1 affected71 at risk
Paresthesia	Nervous system disorders	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0011 events1 affected71 at risk
Dystonia	Nervous system disorders	MedDRA (16.0)	Systematic Assessment		EG0000 events0 affected69 at risk EG0011 events1 affected71 at risk
Death	General disorders	MedDRA (16.0)	Systematic Assessment	Included in All-cause mortality	EG0001 events1 affected69 at risk EG0010 events0 affected71 at risk
General physical health deterioration	General disorders	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0010 events0 affected71 at risk
Multi- organ failure	General disorders	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0010 events0 affected71 at risk
Sudden death	General disorders	MedDRA (16.0)	Systematic Assessment	Included in All-cause mortality	EG0001 events1 affected69 at risk EG0010 events0 affected71 at risk
Embolism	Vascular disorders	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0010 events0 affected71 at risk
Hypotension	Vascular disorders	MedDRA (16.0)	Systematic Assessment		EG0000 events0 affected69 at risk EG0012 events2 affected71 at risk
Vena Cava Thrombosis	Vascular disorders	MedDRA (16.0)	Systematic Assessment		EG0000 events0 affected69 at risk EG0011 events1 affected71 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0000 events0 affected69 at risk EG0011 events1 affected71 at risk
Infusion Related Reaction	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0000 events0 affected69 at risk EG0011 events1 affected71 at risk
Subdural hematoma	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0000 events0 affected69 at risk EG0011 events1 affected71 at risk
Excoriation	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0010 events0 affected71 at risk
Cardiac failure acute	Cardiac disorders	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0011 events1 affected71 at risk
Acute Kidney injury	Renal and urinary disorders	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0011 events1 affected71 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0010 events0 affected71 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0010 events0 affected71 at risk
Anaphylactic reaction	Immune system disorders	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0010 events0 affected71 at risk
Eye hemorrhage	Eye disorders	MedDRA (16.0)	Systematic Assessment		EG0000 events0 affected69 at risk EG0011 events1 affected71 at risk
Cholecystis acute	Hepatobiliary disorders	MedDRA (16.0)	Systematic Assessment		EG0001 events1 affected69 at risk EG0010 events0 affected71 at risk
Transaminases increased	Investigations	MedDRA (16.0)	Systematic Assessment		EG0000 events0 affected69 at risk EG0011 events1 affected71 at risk
Tumor hemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Systematic Assessment		EG0000 events0 affected69 at risk EG0012 events2 affected71 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhea	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG00034 affected69 at risk EG00141 affected71 at risk
Nausea	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG00031 affected69 at risk EG00132 affected71 at risk
Vomiting	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG00025 affected69 at risk EG00124 affected71 at risk
Constipation	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0009 affected69 at risk EG00119 affected71 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0006 affected69 at risk EG00118 affected71 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0009 affected69 at risk EG0018 affected71 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0005 affected69 at risk EG0015 affected71 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0005 affected69 at risk EG0011 affected71 at risk
Proctalgia	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0005 affected69 at risk EG0011 affected71 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0004 affected69 at risk EG0014 affected71 at risk
Rectal hemorrhage	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0004 affected69 at risk EG0011 affected71 at risk
Asthenia	General disorders	MedDRA (16.0)	Systematic Assessment	EG00022 affected69 at risk EG00121 affected71 at risk
Fatigue	General disorders	MedDRA (16.0)	Systematic Assessment	EG00016 affected69 at risk EG00118 affected71 at risk
Pyrexia	General disorders	MedDRA (16.0)	Systematic Assessment	EG0006 affected69 at risk EG00114 affected71 at risk
Mucosal inflammation	General disorders	MedDRA (16.0)	Systematic Assessment	EG0007 affected69 at risk EG0016 affected71 at risk
Edema peripheral	General disorders	MedDRA (16.0)	Systematic Assessment	EG0003 affected69 at risk EG0016 affected71 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG00013 affected69 at risk EG00113 affected71 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG00011 affected69 at risk EG00116 affected71 at risk
Paresthesia	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG00010 affected69 at risk EG00110 affected71 at risk
Headache	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0007 affected69 at risk EG00110 affected71 at risk
Dysgeusia	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0004 affected69 at risk EG00112 affected71 at risk
Dizziness	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0004 affected69 at risk EG0014 affected71 at risk
Dysesthesia	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0003 affected69 at risk EG0014 affected71 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment	EG00023 affected69 at risk EG00126 affected71 at risk
Anemia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment	EG00019 affected69 at risk EG00128 affected71 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment	EG00014 affected69 at risk EG00116 affected71 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment	EG00010 affected69 at risk EG00113 affected71 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG00019 affected69 at risk EG00120 affected71 at risk
Hypertriglyceridemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG00011 affected69 at risk EG00117 affected71 at risk
Hyperkalemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0004 affected69 at risk EG0018 affected71 at risk
Hyperglycemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0003 affected69 at risk EG00110 affected71 at risk
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0005 affected69 at risk EG0015 affected71 at risk
Hypernatraemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0004 affected69 at risk EG0011 affected71 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0003 affected69 at risk EG0014 affected71 at risk
Hypokalemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected69 at risk EG0014 affected71 at risk
Urinary tract infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0007 affected69 at risk EG0016 affected71 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0006 affected69 at risk EG0016 affected71 at risk
Influenza	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0006 affected69 at risk EG0015 affected71 at risk
Respiratory tract infection viral	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0004 affected69 at risk EG0013 affected71 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0004 affected69 at risk EG0011 affected71 at risk
Weight decreased	Investigations	MedDRA (16.0)	Systematic Assessment	EG00016 affected69 at risk EG00112 affected71 at risk
Alanine aminotransferase increased	Investigations	MedDRA (16.0)	Systematic Assessment	EG0008 affected69 at risk EG0019 affected71 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (16.0)	Systematic Assessment	EG0004 affected69 at risk EG00110 affected71 at risk
Blood creatinine increased	Investigations	MedDRA (16.0)	Systematic Assessment	EG0002 affected69 at risk EG0016 affected71 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA (16.0)	Systematic Assessment	EG0002 affected69 at risk EG0015 affected71 at risk
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0007 affected69 at risk EG0017 affected71 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0005 affected69 at risk EG0012 affected71 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0004 affected69 at risk EG0018 affected71 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0003 affected69 at risk EG0014 affected71 at risk
Hypertension	Vascular disorders	MedDRA (16.0)	Systematic Assessment	EG00017 affected69 at risk EG00120 affected71 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0007 affected69 at risk EG00111 affected71 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0004 affected69 at risk EG0019 affected71 at risk
Dysaesthesia pharynx	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0005 affected69 at risk EG0012 affected71 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected69 at risk EG0015 affected71 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected69 at risk EG0015 affected71 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0006 affected69 at risk EG0015 affected71 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0006 affected69 at risk EG0015 affected71 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected69 at risk EG0015 affected71 at risk
Proteinuria	Renal and urinary disorders	MedDRA (16.0)	Systematic Assessment	EG0007 affected69 at risk EG0015 affected71 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment	EG0002 affected69 at risk EG0014 affected71 at risk

ID	Term
D015179	Colorectal Neoplasms
D009362	Neoplasm Metastasis

Ancestor Terms

ID	Term
D007414	Intestinal Neoplasms
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases
D003108	Colonic Diseases
D007410	Intestinal Diseases
D012002	Rectal Diseases
D009385	Neoplastic Processes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
C000631406	BEVZ92
D005472	Fluorouracil
D000077150	Oxaliplatin
D000077146	Irinotecan
D000068258	Bevacizumab

Ancestor Terms

ID	Term
D014498	Uracil
D011744	Pyrimidinones
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D056831	Coordination Complexes
D009930	Organic Chemicals
D002166	Camptothecin
D000470	Alkaloids
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

ParticipantsBG002140

Units	Counts
Participants	OG00055 OG00158

Units	Counts
Participants	OG00071 OG00171