Efficacy and Safety Study of ABP 215 Compared With Bevacizumab in Patients With Advanced Non-Small Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT01966003
• Recruitment Status: Completed
• First Posted: October 21, 2013
• Results First Posted: October 19, 2017
• Last Update Posted: October 19, 2017
• Sponsor: Amgen
• Collaborator: Actavis Inc.
• Information provided by (Responsible Party): Amgen

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Non-small Cell Lung Cancer Metastatic
• Interventions: Drug: Carboplatin; Drug: Paclitaxel; Drug: ABP 215; Drug: Bevacizumab
• Enrollment: 642

Participant Flow

Recruitment Details	This study was conducted at 101 sites (14 sites in the US, 11 in Russia, 10 in Australia, 9 in Germany, 8 in Poland, 7 in Hungary, 7 in Romania, 6 in Italy, 6 in Spain, 5 in Bulgaria, 5 in Greece, 3 in the Czech Republic, 3 in Mexico, 3 in Taiwan, 2 in the Netherlands, 1 in Canada, and 1 in Hong Kong).
Pre-assignment Details	Eligible participants were randomized in a 1:1 ratio to receive ABP 215 or bevacizumab. Participants were stratified by geographic region (Eastern Europe vs Western Europe vs Asia Pacific/Other vs North America), Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1), and sex.

Arm/Group Title	ABP 215	Bevacizumab
Arm/Group Description	Participants received 15 mg/kg ABP 215 administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.	Participants received bevacizumab 15 mg/kg administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.
Period Title: Overall Study
Started	328	314
Received Study Drug	324	309
Completed	58	44
Not Completed	270	270
Reason Not Completed
Death	43	36
Protocol Violation	6	4
Lost to Follow-up	4	3
Physician Decision	12	13
Withdrawal by Subject	29	19
Plan to Receive Other Anticancer Therapy	131	127
Plan to Receive Commercial Bevacizumab	44	67
Other	1	1

Baseline Characteristics

Arm/Group Title		ABP 215	Bevacizumab	Total
Arm/Group Description		Participants received 15 mg/kg ABP 215 administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.	Participants received bevacizumab 15 mg/kg administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.	Total of all reporting groups
Overall Number of Baseline Participants		328	314	642
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	328 participants	314 participants	642 participants
		61.6 (9.09)	61.6 (8.88)	61.6 (8.98)
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	328 participants	314 participants	642 participants
< 65 years		199	191	390
≥ 65 years		129	123	252
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	328 participants	314 participants	642 participants
	Female	132 40.2%	126 40.1%	258 40.2%
	Male	196 59.8%	188 59.9%	384 59.8%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	328 participants	314 participants	642 participants
	Hispanic or Latino	14 4.3%	16 5.1%	30 4.7%
	Not Hispanic or Latino	314 95.7%	298 94.9%	612 95.3%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	328 participants	314 participants	642 participants
White		315	300	615
Black or African American		2	5	7
Asian		6	7	13
American Indian or Alaska Native		2	0	2
Native Hawaiian or other Pacific Islander		1	0	1
Other		4	2	6
		[1] Measure Description: Participants were allowed to choose multiple races.
Geographic Region; Measure Type: Number; Unit of measure: Participants	Number Analyzed	328 participants	314 participants	642 participants
Eastern Europe		189	186	375
Western Europe		78	76	154
North America		31	26	57
Asia Pacific/Other		30	26	56
Eastern Cooperative Oncology Group (ECOG) Performance Status [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	328 participants	314 participants	642 participants
Grade 0		127	117	244
Grade 1		201	197	398
		[1] Measure Description: A scale to assess a patient's disease status. 0 = Fully active, able to carry out all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out work of a light nature; 2 = Ambulatory and capable of all self care, unable to carry out any work activities. Up and about > 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair > 50% of waking hours; 4 = Completely disabled, confined to bed or chair; 5 = Dead.

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With an Objective Response
Description	Tumor assessments were performed by central, independent, blinded radiologists according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 using computed tomography (CT) or magnetic resonance imaging (MRI) scans of the chest and abdomen. Objective response 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. CR: Disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes must be reduced in short axis to < 10 mm. PR: Disappearance of all target lesions with persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, and no new lesions, or, at least a 30% decrease in the sum of diameters of target lesions, with no progression of existing non-target lesions and no new lesions.
Time Frame	Disease assessments were performed at weeks 1, 7, 13, 19, and approximately every 9 weeks thereafter. The mean actual follow-up time from randomization was 4.7 and 5.0 months for ABP 215 and bevacizumab, respectively.

Outcome Measure Data

Analysis Population Description

Intent-to-treat population which consisted of all randomized participants.

Arm/Group Title	ABP 215	Bevacizumab
Arm/Group Description:	Participants received 15 mg/kg ABP 215 administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.	Participants received bevacizumab 15 mg/kg administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.
Overall Number of Participants Analyzed	328	314
Measure Type: Number; Unit of Measure: percentage of participants
	39.0	41.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABP 215, Bevacizumab
	Comments	The risk ratio (ABP 215/Bevacizumab) and 90% confidence interval (CI) were estimated using a generalized linear model adjusted for the stratification factors (region, sex, and ECOG performance status).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Clinical equivalence of the primary endpoint was demonstrated by comparing the 2-sided 90% CI of the risk ratio in objective response rate between ABP 215 and bevacizumab with an equivalence margin of (0.67, 1.5).
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 90%; 0.80 to 1.09
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ABP 215, Bevacizumab
	Comments	Risk difference (ABP 215 - Bevacizumab) and 90% CI were estimated using a generalized linear model adjusted for the randomization stratification factors geographic region, ECOG performance status, and sex.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-2.90
	Confidence Interval	(2-Sided) 90%; -9.26 to 3.45
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Duration of Response
Description	Duration of response (DOR) was calculated as the time from the first objective response (PR or CR) to disease progression per RECIST v1.1 based on the central, independent, blinded radiologists' review. DOR was only calculated for participants with an objective response. For responders not meeting the criterion for progression by the end of the study, DOR was censored at the date of the last evaluable tumor assessment. Progressive Disease was defined as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm, or, unequivocal progression of existing non-target lesions, or any new lesions.
Time Frame	Disease assessments were performed at weeks 1, 7, 13, 19, and approximately every 9 weeks thereafter. The mean actual follow-up time from randomization was 4.7 and 5.0 months for ABP 215 and bevacizumab, respectively.

Outcome Measure Data

Analysis Population Description

Intent-to-treat population with an objective response

Arm/Group Title	ABP 215	Bevacizumab
Arm/Group Description:	Participants received 15 mg/kg ABP 215 administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.	Participants received bevacizumab 15 mg/kg administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.
Overall Number of Participants Analyzed	128	131
Median (95% Confidence Interval); Unit of Measure: months
	5.8; (4.9 to 7.7)	5.6; (5.1 to 6.3)

3. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival (PFS) was defined as the time from the randomization date to the date of disease progression using RECIST v1.1 based on the central, independent, blinded radiologists' review, or death. Participants who were alive and did not meet the criteria for progression by the end of the study were censored at their last evaluable disease assessment date. Participants with no evaluable tumor assessments after randomization who did not die by the end of the study were censored on the randomization date. Progressive Disease was defined as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm, or, unequivocal progression of existing non-target lesions, or any new lesions.
Time Frame	From randomization until the end of study; The mean actual follow-up time from randomization was 4.7 and 5.0 months for ABP 215 and bevacizumab, respectively.

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	ABP 215	Bevacizumab
Arm/Group Description:	Participants received 15 mg/kg ABP 215 administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.	Participants received bevacizumab 15 mg/kg administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.
Overall Number of Participants Analyzed	328	314
Median (95% Confidence Interval); Unit of Measure: months
	6.6; (6.3 to 7.9)	7.9; (6.6 to 8.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABP 215, Bevacizumab
	Comments	The hazard ratio for ABP 215 relative to bevacizumab was based on a stratified Cox proportional hazards model. Stratification factors are geographic region, ECOG performance status, and sex.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 90%; 0.83 to 1.29
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Adverse events (AEs) were graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4, and according to the following scale: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death due to AE. A serious adverse event (SAE) is defined as an AE that meets at least 1 of the following serious criteria: fatal; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event
Time Frame	up to 19 weeks

Outcome Measure Data

Analysis Population Description

Safety analysis population consisted of all participants who received any amount of study drug.

Arm/Group Title	ABP 215	Bevacizumab
Arm/Group Description:	Participants received 15 mg/kg ABP 215 administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.	Participants received bevacizumab 15 mg/kg administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.
Overall Number of Participants Analyzed	324	309
Measure Type: Number; Unit of Measure: participants
Any adverse event	308	289
Any grade ≥ 3 adverse event	139	137
Any fatal adverse event	13	11
Any serious adverse event	85	71
Any AE leading to discontinuation of study drug	61	53
Any AE leading to discontinuation of chemotherapy	74	59
Any AE leading to dose delay of study drug	73	69
Any AE leading to dose delay of any chemotherapy	86	83
Any AE leading to dose reduction of chemotherapy	48	49

5. Secondary Outcome

Title	Number of Participants Who Developed Anti-drug Antibodies
Description	Two validated assays were used to detect the presence of anti-ABP 215 antibodies. Samples were first tested in an electrochemiluminescence (ECL)- based bridging immunoassay to detect antibodies capable of binding to ABP 215 (Binding Antibody Assay). Samples confirmed to be positive for binding antibodies were subsequently tested in a non-cell based target binding assay to determine neutralizing activity against ABP 215 (Neutralizing Antibody Assay). If a post-dose sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the sample was defined as positive for neutralizing antibodies.
Time Frame	44 weeks (6 months after end of treatment)

Outcome Measure Data

Analysis Population Description

Safety analysis population with available data

Arm/Group Title	ABP 215	Bevacizumab
Arm/Group Description:	Participants received 15 mg/kg ABP 215 administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.	Participants received bevacizumab 15 mg/kg administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.
Overall Number of Participants Analyzed	294	284
Measure Type: Number; Unit of Measure: participants
Binding antibody positive	4	7
Neutralizing antibody positive	0	0

6. Secondary Outcome

Title	Overall Survival
Description	Overall survival (OS) was defined as the time from the randomization date to date of death. Participants alive at the end of study were censored at the last date known to be alive, derived from dates collected within the study that implied a participant was alive. Participants were followed for survival status during the treatment phase and thereafter every 9 weeks until the end of the clinical study, consent was withdrawn, they were lost to follow-up, died, or had proscribed therapy (eg, commercial bevacizumab, non-study anti-cancer treatment).
Time Frame	From randomization until the end of study; The mean actual follow-up time from randomization was 4.7 and 5.0 months for ABP 215 and bevacizumab, respectively.

Outcome Measure Data

Analysis Population Description

Safety analysis population

Arm/Group Title	ABP 215	Bevacizumab
Arm/Group Description:	Participants received 15 mg/kg ABP 215 administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.	Participants received bevacizumab 15 mg/kg administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.
Overall Number of Participants Analyzed	324	309
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (NA to NA)	NA [1]; (14.6 to NA)

[1]

Could not be estimated due to the low number of deaths

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABP 215, Bevacizumab
	Comments	Hazard ratio for ABP 215 relative to bevacizumab, based on a stratified Cox proportional hazards model. Stratification factors are geographic region, ECOG performance status, and sex.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 90%; 0.75 to 1.61
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	19 weeks
Adverse Event Reporting Description	Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Arm/Group Title	ABP 215	Bevacizumab
Arm/Group Description	Participants received 15 mg/kg ABP 215 administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.	Participants received bevacizumab 15 mg/kg administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.
All-Cause Mortality
	ABP 215	Bevacizumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	ABP 215	Bevacizumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	85/324 (26.23%)	71/309 (22.98%)
Blood and lymphatic system disorders
Anaemia † 1	3/324 (0.93%)	6/309 (1.94%)
Febrile neutropenia † 1	11/324 (3.40%)	8/309 (2.59%)
Hypercoagulation † 1	0/324 (0.00%)	1/309 (0.32%)
Neutropenia † 1	6/324 (1.85%)	3/309 (0.97%)
Pancytopenia † 1	0/324 (0.00%)	1/309 (0.32%)
Thrombocytopenia † 1	2/324 (0.62%)	2/309 (0.65%)
Cardiac disorders
Acute left ventricular failure † 1	0/324 (0.00%)	1/309 (0.32%)
Acute myocardial infarction † 1	1/324 (0.31%)	0/309 (0.00%)
Atrial fibrillation † 1	1/324 (0.31%)	1/309 (0.32%)
Cardiac arrest † 1	1/324 (0.31%)	0/309 (0.00%)
Cardiopulmonary failure † 1	1/324 (0.31%)	0/309 (0.00%)
Coronary artery disease † 1	1/324 (0.31%)	0/309 (0.00%)
Paroxysmal arrhythmia † 1	0/324 (0.00%)	1/309 (0.32%)
Pericardial effusion † 1	1/324 (0.31%)	0/309 (0.00%)
Ventricular extrasystoles † 1	1/324 (0.31%)	0/309 (0.00%)
Ear and labyrinth disorders
Vertigo † 1	0/324 (0.00%)	1/309 (0.32%)
Gastrointestinal disorders
Abdominal pain † 1	1/324 (0.31%)	0/309 (0.00%)
Anal haemorrhage † 1	1/324 (0.31%)	0/309 (0.00%)
Constipation † 1	1/324 (0.31%)	0/309 (0.00%)
Diarrhoea † 1	3/324 (0.93%)	2/309 (0.65%)
Diarrhoea haemorrhagic † 1	1/324 (0.31%)	0/309 (0.00%)
Diverticular perforation † 1	0/324 (0.00%)	1/309 (0.32%)
Faecaloma † 1	0/324 (0.00%)	1/309 (0.32%)
Gastrointestinal haemorrhage † 1	1/324 (0.31%)	0/309 (0.00%)
Intestinal perforation † 1	1/324 (0.31%)	1/309 (0.32%)
Large intestinal haemorrhage † 1	1/324 (0.31%)	0/309 (0.00%)
Large intestine perforation † 1	1/324 (0.31%)	1/309 (0.32%)
Melaena † 1	1/324 (0.31%)	0/309 (0.00%)
Mesenteric artery embolism † 1	1/324 (0.31%)	0/309 (0.00%)
Nausea † 1	2/324 (0.62%)	1/309 (0.32%)
Rectal haemorrhage † 1	2/324 (0.62%)	0/309 (0.00%)
Small intestinal obstruction † 1	1/324 (0.31%)	0/309 (0.00%)
Upper gastrointestinal haemorrhage † 1	1/324 (0.31%)	0/309 (0.00%)
Vomiting † 1	2/324 (0.62%)	1/309 (0.32%)
General disorders
Death † 1	2/324 (0.62%)	1/309 (0.32%)
Fatigue † 1	2/324 (0.62%)	0/309 (0.00%)
General physical health deterioration † 1	2/324 (0.62%)	2/309 (0.65%)
Non-cardiac chest pain † 1	1/324 (0.31%)	0/309 (0.00%)
Pyrexia † 1	1/324 (0.31%)	2/309 (0.65%)
Sudden death † 1	0/324 (0.00%)	1/309 (0.32%)
Hepatobiliary disorders
Hepatitis † 1	1/324 (0.31%)	0/309 (0.00%)
Immune system disorders
Hypersensitivity † 1	1/324 (0.31%)	0/309 (0.00%)
Infections and infestations
Abscess soft tissue † 1	0/324 (0.00%)	1/309 (0.32%)
Anal abscess † 1	0/324 (0.00%)	1/309 (0.32%)
Appendicitis † 1	1/324 (0.31%)	0/309 (0.00%)
Bronchopneumonia † 1	0/324 (0.00%)	1/309 (0.32%)
Bronchopulmonary aspergillosis † 1	1/324 (0.31%)	0/309 (0.00%)
Cellulitis † 1	1/324 (0.31%)	0/309 (0.00%)
Cytomegalovirus hepatitis † 1	0/324 (0.00%)	1/309 (0.32%)
Empyema † 1	0/324 (0.00%)	2/309 (0.65%)
Escherichia bacteraemia † 1	1/324 (0.31%)	0/309 (0.00%)
Influenza † 1	1/324 (0.31%)	0/309 (0.00%)
Lower respiratory tract infection † 1	1/324 (0.31%)	0/309 (0.00%)
Lung infection † 1	1/324 (0.31%)	1/309 (0.32%)
Neutropenic infection † 1	0/324 (0.00%)	1/309 (0.32%)
Neutropenic sepsis † 1	1/324 (0.31%)	0/309 (0.00%)
Peritonitis † 1	0/324 (0.00%)	2/309 (0.65%)
Pilonidal cyst † 1	0/324 (0.00%)	1/309 (0.32%)
Pneumonia † 1	6/324 (1.85%)	5/309 (1.62%)
Pseudomonas infection † 1	1/324 (0.31%)	0/309 (0.00%)
Pulmonary sepsis † 1	1/324 (0.31%)	0/309 (0.00%)
Respiratory tract infection † 1	2/324 (0.62%)	2/309 (0.65%)
Sepsis † 1	1/324 (0.31%)	1/309 (0.32%)
Septic shock † 1	1/324 (0.31%)	0/309 (0.00%)
Urinary tract infection † 1	0/324 (0.00%)	1/309 (0.32%)
Injury, poisoning and procedural complications
Brain contusion † 1	1/324 (0.31%)	0/309 (0.00%)
Femoral neck fracture † 1	1/324 (0.31%)	0/309 (0.00%)
Humerus fracture † 1	1/324 (0.31%)	0/309 (0.00%)
Infusion related reaction † 1	0/324 (0.00%)	1/309 (0.32%)
Lumbar vertebral fracture † 1	1/324 (0.31%)	0/309 (0.00%)
Road traffic accident † 1	1/324 (0.31%)	0/309 (0.00%)
Toxicity to various agents † 1	1/324 (0.31%)	0/309 (0.00%)
Investigations
Blood bilirubin increased † 1	1/324 (0.31%)	0/309 (0.00%)
Metabolism and nutrition disorders
Cachexia † 1	1/324 (0.31%)	0/309 (0.00%)
Decreased appetite † 1	0/324 (0.00%)	1/309 (0.32%)
Dehydration † 1	0/324 (0.00%)	2/309 (0.65%)
Hyperglycaemia † 1	1/324 (0.31%)	0/309 (0.00%)
Hyponatraemia † 1	1/324 (0.31%)	0/309 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/324 (0.00%)	1/309 (0.32%)
Back pain † 1	0/324 (0.00%)	1/309 (0.32%)
Musculoskeletal chest pain † 1	1/324 (0.31%)	1/309 (0.32%)
Pathological fracture † 1	1/324 (0.31%)	0/309 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to bone † 1	1/324 (0.31%)	0/309 (0.00%)
Tumour pain † 1	0/324 (0.00%)	1/309 (0.32%)
Nervous system disorders
Brain oedema † 1	0/324 (0.00%)	1/309 (0.32%)
Cerebral ischaemia † 1	2/324 (0.62%)	1/309 (0.32%)
Depressed level of consciousness † 1	1/324 (0.31%)	0/309 (0.00%)
Dysarthria † 1	1/324 (0.31%)	0/309 (0.00%)
Encephalopathy † 1	2/324 (0.62%)	0/309 (0.00%)
Ischaemic cerebral infarction † 1	1/324 (0.31%)	0/309 (0.00%)
Ischaemic stroke † 1	0/324 (0.00%)	1/309 (0.32%)
Migraine † 1	2/324 (0.62%)	0/309 (0.00%)
Paraesthesia † 1	1/324 (0.31%)	0/309 (0.00%)
Seizure † 1	0/324 (0.00%)	1/309 (0.32%)
Spinal cord compression † 1	0/324 (0.00%)	1/309 (0.32%)
Syncope † 1	0/324 (0.00%)	1/309 (0.32%)
Transient ischaemic attack † 1	2/324 (0.62%)	1/309 (0.32%)
Psychiatric disorders
Hallucinations, mixed † 1	1/324 (0.31%)	0/309 (0.00%)
Renal and urinary disorders
Acute kidney injury † 1	0/324 (0.00%)	1/309 (0.32%)
Renal failure † 1	1/324 (0.31%)	0/309 (0.00%)
Respiratory, thoracic and mediastinal disorders
Bronchial fistula † 1	1/324 (0.31%)	1/309 (0.32%)
Chronic obstructive pulmonary disease † 1	1/324 (0.31%)	1/309 (0.32%)
Dyspnoea † 1	3/324 (0.93%)	4/309 (1.29%)
Epistaxis † 1	2/324 (0.62%)	0/309 (0.00%)
Haemoptysis † 1	3/324 (0.93%)	5/309 (1.62%)
Pleural effusion † 1	1/324 (0.31%)	0/309 (0.00%)
Pneumothorax † 1	2/324 (0.62%)	1/309 (0.32%)
Pulmonary artery thrombosis † 1	0/324 (0.00%)	1/309 (0.32%)
Pulmonary embolism † 1	5/324 (1.54%)	6/309 (1.94%)
Pulmonary haemorrhage † 1	0/324 (0.00%)	1/309 (0.32%)
Respiratory distress † 1	1/324 (0.31%)	0/309 (0.00%)
Respiratory failure † 1	2/324 (0.62%)	1/309 (0.32%)
Skin and subcutaneous tissue disorders
Rash generalised † 1	1/324 (0.31%)	0/309 (0.00%)
Subcutaneous emphysema † 1	0/324 (0.00%)	1/309 (0.32%)
Surgical and medical procedures
Prophylaxis † 1	1/324 (0.31%)	0/309 (0.00%)
Vascular disorders
Deep vein thrombosis † 1	1/324 (0.31%)	1/309 (0.32%)
Embolism arterial † 1	1/324 (0.31%)	1/309 (0.32%)
Haematoma † 1	0/324 (0.00%)	1/309 (0.32%)
Hypotension † 1	0/324 (0.00%)	1/309 (0.32%)
Thrombosis † 1	1/324 (0.31%)	0/309 (0.00%)
Venous thrombosis † 1	1/324 (0.31%)	1/309 (0.32%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	ABP 215	Bevacizumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	286/324 (88.27%)	276/309 (89.32%)
Blood and lymphatic system disorders
Anaemia † 1	65/324 (20.06%)	60/309 (19.42%)
Leukopenia † 1	23/324 (7.10%)	23/309 (7.44%)
Neutropenia † 1	55/324 (16.98%)	60/309 (19.42%)
Thrombocytopenia † 1	47/324 (14.51%)	43/309 (13.92%)
Gastrointestinal disorders
Constipation † 1	36/324 (11.11%)	36/309 (11.65%)
Diarrhoea † 1	39/324 (12.04%)	55/309 (17.80%)
Gingival bleeding † 1	9/324 (2.78%)	19/309 (6.15%)
Nausea † 1	82/324 (25.31%)	95/309 (30.74%)
Stomatitis † 1	15/324 (4.63%)	18/309 (5.83%)
Vomiting † 1	37/324 (11.42%)	41/309 (13.27%)
General disorders
Asthenia † 1	49/324 (15.12%)	42/309 (13.59%)
Fatigue † 1	57/324 (17.59%)	59/309 (19.09%)
Pyrexia † 1	19/324 (5.86%)	20/309 (6.47%)
Investigations
Weight decreased † 1	18/324 (5.56%)	16/309 (5.18%)
Metabolism and nutrition disorders
Decreased appetite † 1	54/324 (16.67%)	42/309 (13.59%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	23/324 (7.10%)	29/309 (9.39%)
Back pain † 1	14/324 (4.32%)	19/309 (6.15%)
Bone pain † 1	20/324 (6.17%)	25/309 (8.09%)
Myalgia † 1	39/324 (12.04%)	44/309 (14.24%)
Pain in extremity † 1	24/324 (7.41%)	20/309 (6.47%)
Nervous system disorders
Dizziness † 1	13/324 (4.01%)	25/309 (8.09%)
Headache † 1	28/324 (8.64%)	24/309 (7.77%)
Neuropathy peripheral † 1	56/324 (17.28%)	38/309 (12.30%)
Paraesthesia † 1	28/324 (8.64%)	40/309 (12.94%)
Peripheral sensory neuropathy † 1	18/324 (5.56%)	16/309 (5.18%)
Polyneuropathy † 1	20/324 (6.17%)	22/309 (7.12%)
Renal and urinary disorders
Proteinuria † 1	26/324 (8.02%)	19/309 (6.15%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	26/324 (8.02%)	21/309 (6.80%)
Dyspnoea † 1	24/324 (7.41%)	24/309 (7.77%)
Epistaxis † 1	44/324 (13.58%)	39/309 (12.62%)
Skin and subcutaneous tissue disorders
Alopecia † 1	140/324 (43.21%)	127/309 (41.10%)
Vascular disorders
Hypertension † 1	51/324 (15.74%)	41/309 (13.27%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.

Results Point of Contact

• Name/Title: Study Director
• Organization: Amgen Inc.
• Phone: 866-572-6436

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Thatcher N, Goldschmidt JH, Thomas M, Schenker M, Pan Z, Paz-Ares Rodriguez L, Breder V, Ostoros G, Hanes V. Efficacy and Safety of the Biosimilar ABP 215 Compared with Bevacizumab in Patients with Advanced Nonsquamous Non-small Cell Lung Cancer (MAPLE): A Randomized, Double-blind, Phase III Study. Clin Cancer Res. 2019 Apr 1;25(7):2088-2095. doi: 10.1158/1078-0432.CCR-18-2702. Epub 2019 Jan 7. Erratum in: Clin Cancer Res. 2019 May 15;25(10):3193.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT01966003
• Other Study ID Numbers: 20120265; 2013-000738-36 ( EudraCT Number )
• First Submitted: October 4, 2013
• First Posted: October 21, 2013
• Results First Submitted: September 21, 2017
• Results First Posted: October 19, 2017
• Last Update Posted: October 19, 2017