A Comparative Study Of PF-06439535 Plus Paclitaxel-Carboplatin And Bevacizumab Plus Paclitaxel-Carboplatin Patients With Advanced Non-Squamous NSCLC

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ClinicalTrials.gov Identifier: NCT02364999

Recruitment Status : Completed

First Posted : February 18, 2015

Results First Posted : June 27, 2018

Last Update Posted : February 7, 2019

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Sponsor:

Information provided by (Responsible Party):

Pfizer

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition	Non-Small Cell Lung Cancer
Interventions	Drug: Bevacizumab-Pfizer Drug: Bevacizumab-EU Drug: Paclitaxel Drug: Carboplatin
Enrollment	719

Participant Flow

Recruitment Details
Pre-assignment Details	A total of 719 participants were enrolled in this study, and 5 of them did not receive any therapy. One (1) additional participant received only chemotherapy, and did not receive blinded bevacizumab.


Arm/Group Title	PF-06439535	Bevacizumab-EU
Arm/Group Description	Participants received up to a maxim...	Participants received up to a maxim...
Arm/Group Description	Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.	Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Period Title: Overall Study
Started	358	361
Received Treatment	356	358
Completed	193	188
Not Completed	165	173
Reason Not Completed
Death	136	138
Lost to Follow-up	10	15
Protocol Violation	3	2
Withdrawal by Subject	14	14
Other	0	1
Randomized but did not receive treatment	2	3

Baseline Characteristics

Arm/Group Title		PF-06439535	Bevacizumab-EU	Total
Arm/Group Description		Participants received up to a maxim...	Participants received up to a maxim...	Total of all reporting groups
Arm/Group Description		Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.	Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.	Total of all reporting groups
Overall Number of Baseline Participants		358	361	719
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Baseline analysis population is the Intent-to-Treat (ITT) population and it included all participants who were randomized to study treatment.
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	358 participants	361 participants	719 participants
		61.7 (9.5)	60.9 (8.9)	61.3 (9.2)
Age, Customized Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	358 participants	361 participants	719 participants
18-44 years		19 5.3%	17 4.7%	36 5.0%
45-64 years		198 55.3%	222 61.5%	420 58.4%
>= 65 years		141 39.4%	122 33.8%	263 36.6%
Sex/Gender, Customized Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	358 participants	361 participants	719 participants
Female		121 33.8%	131 36.3%	252 35.0%
Male		237 66.2%	230 63.7%	467 65.0%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	358 participants	361 participants	719 participants
WHITE		319 89.1%	319 88.4%	638 88.7%
BLACK		3 0.8%	1 0.3%	4 0.6%
ASIAN		36 10.1%	40 11.1%	76 10.6%
OTHER		0 0.0%	1 0.3%	1 0.1%

Outcome Measures

1.Primary Outcome


Title	Objective Response Rate (ORR) by Week 19
Description	ORR refers to percentage of participants who achieved complete respons...
Description	ORR refers to percentage of participants who achieved complete response (CR) or partial response (PR) by Week 19 of the study in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 which was subsequently confirmed by Week 25. A participant achieved CR if both target and non-target lesions achieved CR, no new lesions; achieved PR if target lesions achieved CR or PR, non-target lesions were assessed as non-CR/non-PD (progressive disease), indeterminate or missing, and no new lesions. For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes must decrease to normal size); PR: >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. For non-target lesions, CR: disappearance of all non-target lesions and normalization of tumor marker levels and all lymph nodes must be normal in size; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits.
Time Frame	25 weeks

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (ITT) population was used for analysis of ORR, and it included all participants who were randomized to study treatment.


Arm/Group Title	PF-06439535	Bevacizumab-EU
Arm/Group Description:	Participants received up to a maxim...	Participants received up to a maxim...
Arm/Group Description:	Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.	Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Overall Number of Participants Analyzed	358	361
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	45.3 (40.01 to 50.57)	44.6 (39.40 to 49.89)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-06439535, Bevacizumab-EU
	Comments	[Not Specified]
	Type of Statistical Test	Equivalence
	Comments	Calculated based on 2-sided Miettinen and Nurminen method without strata for risk difference for confirmed response. EU equivalence margins (95% CI in -13% to 13%).

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.6531
	Confidence Interval	(2-Sided) 95% -6.6080 to 7.9082
	Estimation Comments	PF-06439535 vs Bevacizumab-EU

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-06439535, Bevacizumab-EU
	Comments	[Not Specified]
	Type of Statistical Test	Equivalence
	Comments	Calculated based on 2-sided Miettinen and Nurminen method without strata for risk ratio for confirmed response. US equivalence margins (90% CI in 0.73 to 1.37).

Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.0146
	Confidence Interval	(2-Sided) 90% 0.8856 to 1.1625
	Estimation Comments	PF-06439535 vs Bevacizumab-EU

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PF-06439535, Bevacizumab-EU
	Comments	[Not Specified]
	Type of Statistical Test	Equivalence
	Comments	Calculated based on 2-sided Miettinen and Nurminen method without strata for risk ratio for confirmed response. Japan equivalence margins (95% CI in 0.729 to 1.371).

Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.0146
	Confidence Interval	(2-Sided) 95% 0.8628 to 1.1933
	Estimation Comments	PF-06439535 vs Bevacizumab-EU

2.Secondary Outcome


Title	Number of Participants With Treatment-Emergent Adverse Events
Description	AE was defined as any untoward medical occurrence in a clinical invest...
Description	AE was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causal relationship to study treatment. Treatment-emergent AEs (TEAEs) were defined as AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Causality to study treatment was determined by the investigator. Severity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Time Frame	55 weeks

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized and received at least 1 dose of study treatment.


Arm/Group Title	PF-06439535	Bevacizumab-EU
Arm/Group Description:	Participants received up to a maxim...	Participants received up to a maxim...
Arm/Group Description:	Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.	Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Overall Number of Participants Analyzed	356	358
Measure Type: Count of Participants Unit of Measure: Participants
All-causality AE	344 96.6%	347 96.9%
All-causality SAE	81 22.8%	80 22.3%
Bevacizumab-related AE	190 53.4%	199 55.6%
Bevacizumab-related SAE	23 6.5%	17 4.7%
Grade 1 all-causality AE	32 9.0%	41 11.5%
Grade 2 all-causality AE	141 39.6%	134 37.4%
Grade 3 all-causality AE	125 35.1%	104 29.1%
Grade 4 all-causality AE	25 7.0%	44 12.3%
Grade 5 all-causality AE	21 5.9%	24 6.7%

3.Secondary Outcome


Title	Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Description	Laboratory evaluation included hematology (hemoglobin, white blood cel...
Description	Laboratory evaluation included hematology (hemoglobin, white blood cells, platelets and absolute neutrophil count), blood chemistry (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, serum or plasma creatinine, sodium, potassium, total calcium, magnesium, blood urea nitrogen or urea, and albumin ), coagulation (international normalized ratio for prothrombin time and activated partial thromboplastin time) and urinalysis (dipstick followed by a quantitative urine protein analysis for results of 2+ or greater).
Time Frame	55 weeks

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized and received at least 1 dose of study treatment, and had laboratory evaluation done.


Arm/Group Title	PF-06439535	Bevacizumab-EU
Arm/Group Description:	Participants received up to a maxim...	Participants received up to a maxim...
Arm/Group Description:	Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.	Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Overall Number of Participants Analyzed	342	348
Measure Type: Count of Participants Unit of Measure: Participants
	303 88.6%	304 87.4%

4.Secondary Outcome


Title	Duration of Response (DOR)
Description	DOR was defined as the time from date of the first documentation of ob...
Description	DOR was defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of PD or to death due to any cause in the absence of documented PD. DOR was based on the Brookmeyer and Crowley method.
Time Frame	55 weeks

Outcome Measure Data

Analysis Population Description

The analysis population included participants in ITT population (all participants who were randomized to study treatment) who had a confirmed objective response achieved by Week 19.


Arm/Group Title	PF-06439535	Bevacizumab-EU
Arm/Group Description:	Participants received up to a maxim...	Participants received up to a maxim...
Arm/Group Description:	Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.	Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Overall Number of Participants Analyzed	162	161
Median (95% Confidence Interval) Unit of Measure: weeks
	36.3 (31.6 to 43.6)	28.7 (27.0 to 36.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-06439535, Bevacizumab-EU
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Hazard ratio of PF-06439535 versus Bevacizumab-EU; a hazard ratio =1 indicated no difference in progressive disease(PD)/death between 2 reporting groups; >1 indicated an increase in PD/death in PF-06439535; <1 indicated an increase in PD/death in bevacizumab-EU.

Statistical Test of Hypothesis	P-Value	0.1077
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Stratified by smoking, sex and region.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.800
	Confidence Interval	(2-Sided) 95% 0.608 to 1.051
	Estimation Comments	[Not Specified]

5.Secondary Outcome


Title	Progression Free Survival Rate at 55 Weeks
Description	This outcome measure refers to the possibility of being progression fr...
Description	This outcome measure refers to the possibility of being progression free at 55 weeks since start of study treatment, estimated from the Kaplan-Meier curve using the product-limit method.
Time Frame	55 weeks

Outcome Measure Data

Analysis Population Description

The ITT population was used for analysis, and it included all participants who were randomized to study treatment.


Arm/Group Title	PF-06439535	Bevacizumab-EU
Arm/Group Description:	Participants received up to a maxim...	Participants received up to a maxim...
Arm/Group Description:	Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.	Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Overall Number of Participants Analyzed	358	361
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	32.3 (26.9 to 37.8)	30.5 (25.3 to 35.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-06439535, Bevacizumab-EU
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Hazard ratio of PF-06439535 versus Bevacizumab-EU; a hazard ratio =1 indicated no difference in progressive disease(PD)/death between 2 reporting groups; >1 indicated an increase in PD/death in PF-06439535; <1 indicated an increase in PD/death in bevacizumab-EU.

Statistical Test of Hypothesis	P-Value	0.4492
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Stratified by smoking, sex and region.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.931
	Confidence Interval	95% 0.777 to 1.116
	Estimation Comments	[Not Specified]

6.Secondary Outcome


Title	Survival Rate at 55 Weeks
Description	This outcome measure refers to the possibility of being alive at 55 we...
Description	This outcome measure refers to the possibility of being alive at 55 weeks since start of study treatment, estimated from the Kaplan-Meier curve using the product-limit method.
Time Frame	55 weeks

Outcome Measure Data

Analysis Population Description

The ITT population was used for analysis, and it included all participants who were randomized to study treatment.


Arm/Group Title	PF-06439535	Bevacizumab-EU
Arm/Group Description:	Participants received up to a maxim...	Participants received up to a maxim...
Arm/Group Description:	Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.	Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Overall Number of Participants Analyzed	358	361
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	65.8 (60.5 to 70.6)	64.1 (58.6 to 69.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-06439535, Bevacizumab-EU
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Hazard ratio of PF-06439535 versus Bevacizumab-EU; a hazard ratio =1 indicated no difference in progressive disease(PD)/death between 2 reporting groups; >1 indicated an increase in PD/death in PF-06439535; <1 indicated an increase in PD/death in bevacizumab-EU.

Statistical Test of Hypothesis	P-Value	0.4726
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Stratified by smoking, sex and region.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.918
	Confidence Interval	(2-Sided) 95% 0.729 to 1.157
	Estimation Comments	[Not Specified]

7.Secondary Outcome


Title	Serum Concentration of Bevacizumab up to 1 Year
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Pre-dose from Cycle 1 to Cycle 17, 2.5 hours post-dose in Cycle 1, and 1.5 hours post-dose in Cycle 5

Outcome Measure Data

Analysis Population Description

The analysis population included all participants in the per-protocol population (all participants who were randomized and received study treatment as planned and had no major protocol deviations) who had at least 1 drug concentration measurement after administration of study treatment.


Arm/Group Title		PF-06439535	Bevacizumab-EU
Arm/Group Description:		Participants received up to a maxim...	Participants received up to a maxim...
Arm/Group Description:		Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.	Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Overall Number of Participants Analyzed		351	354
Mean (Standard Deviation) Unit of Measure: ng/mL
Pre-dose in Cycle 1	Number Analyzed	333 participants	338 participants
Pre-dose in Cycle 1		68.08 (705.53)	116.4 (1032.1)
2.5 hours post-dose in Cycle 1	Number Analyzed	319 participants	326 participants
2.5 hours post-dose in Cycle 1		280000 (103260)	302200 (100360)
Pre-dose in Cycle 2	Number Analyzed	310 participants	326 participants
Pre-dose in Cycle 2		54350 (44479)	58930 (49452)
Pre-dose in Cycle 3	Number Analyzed	206 participants	211 participants
Pre-dose in Cycle 3		81090 (48671)	83350 (32384)
Pre-dose in Cycle 4	Number Analyzed	277 participants	299 participants
Pre-dose in Cycle 4		100900 (54979)	99750 (50531)
Pre-dose in Cycle 5	Number Analyzed	257 participants	271 participants
Pre-dose in Cycle 5		105300 (48469)	110000 (65416)
1.5 hours post-dose in Cycle 5	Number Analyzed	192 participants	201 participants
1.5 hours post-dose in Cycle 5		360700 (131170)	377200 (142250)
Pre-dose in Cycle 6	Number Analyzed	244 participants	268 participants
Pre-dose in Cycle 6		112000 (40825)	116700 (53844)
Pre-dose in Cycle 7	Number Analyzed	192 participants	214 participants
Pre-dose in Cycle 7		117300 (53844)	122100 (47793)
Pre-dose in Cycle 8	Number Analyzed	195 participants	208 participants
Pre-dose in Cycle 8		123600 (48893)	126400 (52985)
Pre-dose in Cycle 9	Number Analyzed	184 participants	193 participants
Pre-dose in Cycle 9		127200 (46200)	140900 (62548)
Pre-dose in Cycle 10	Number Analyzed	170 participants	179 participants
Pre-dose in Cycle 10		125700 (50769)	135900 (53975)
Pre-dose in Cycle 11	Number Analyzed	170 participants	169 participants
Pre-dose in Cycle 11		129500 (61329)	135600 (54531)
Pre-dose in Cycle 12	Number Analyzed	141 participants	138 participants
Pre-dose in Cycle 12		135200 (64560)	136300 (51312)
Pre-dose in Cycle 13	Number Analyzed	136 participants	121 participants
Pre-dose in Cycle 13		130900 (58093)	139700 (53750)
Pre-dose in Cycle 14	Number Analyzed	131 participants	117 participants
Pre-dose in Cycle 14		128000 (50840)	136200 (53439)
Pre-dose in Cycle 15	Number Analyzed	103 participants	104 participants
Pre-dose in Cycle 15		134000 (55933)	134000 (49663)
Pre-dose in Cycle 16	Number Analyzed	92 participants	95 participants
Pre-dose in Cycle 16		137000 (54813)	128600 (49742)
Pre-dose in Cycle 17	Number Analyzed	90 participants	92 participants
Pre-dose in Cycle 17		134800 (86847)	127500 (52784)

8.Secondary Outcome


Title	Number of Participants With Anti-Drug Antibody (ADA)
Description	ADA assay was performed using a sensitive, specific, and semi-quantita...
Description	ADA assay was performed using a sensitive, specific, and semi-quantitative electrochemiluminescent (ECL) method, which used biotinylated- and ruthenium-labeled PF-06439535 as reagents. Samples with ADA titer greater than or equal to (>=) 2.29 were considered positive.
Time Frame	55 weeks

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized and received at least 1 dose of study treatment.


Arm/Group Title		PF-06439535	Bevacizumab-EU
Arm/Group Description:		Participants received up to a maxim...	Participants received up to a maxim...
Arm/Group Description:		Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.	Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Overall Number of Participants Analyzed		356	358
Measure Type: Count of Participants Unit of Measure: Participants
Cycle 1 pre-dose	Number Analyzed	351 participants	353 participants
Cycle 1 pre-dose		1 0.3%	3 0.8%
Overall (post-treatment)	Number Analyzed	339 participants	350 participants
Overall (post-treatment)		5 1.5%	5 1.4%

9.Secondary Outcome


Title	Number of Participants With Neutralizing Antibody (NAb)
Description	Only samples that were confirmed positive for ADA were further tested ...
Description	Only samples that were confirmed positive for ADA were further tested for NAb. The NAb analysis was conducted using a single validated quasi-quantitative enzyme-linked immunosorbent assay (ELISA) that utilized PF-06439535 as a reagent. Samples with NAb titer >=1.70 were considered positive.
Time Frame	55 weeks

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who had positive ADA results at any time point.


Arm/Group Title		PF-06439535	Bevacizumab-EU
Arm/Group Description:		Participants received up to a maxim...	Participants received up to a maxim...
Arm/Group Description:		Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.	Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Overall Number of Participants Analyzed		6	7
Measure Type: Count of Participants Unit of Measure: Participants
Cycle 1 pre-dose	Number Analyzed	1 participants	3 participants
Cycle 1 pre-dose		1 100.0%	0 0.0%
Overall (post-treatment)	Number Analyzed	5 participants	5 participants
Overall (post-treatment)		0 0.0%	3 60.0%

Adverse Events

Time Frame	55 weeks
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.

Arm/Group Title	PF-06439535		Bevacizumab-EU		Total
Arm/Group Description	Participants received up to a maxim...		Participants received up to a maxim...		This reporting group include all pa...
Arm/Group Description	Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.		Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.		This reporting group include all participants who received at least 1 dose of study treatment from PF-06439535 and Bevacizumab-EU groups.
All-Cause Mortality
	PF-06439535		Bevacizumab-EU		Total
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	144/356 (40.45%)		149/358 (41.62%)		293/714 (41.04%)
Serious Adverse Events Serious Adverse Events
	PF-06439535		Bevacizumab-EU		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	81/356 (22.75%)		80/358 (22.35%)		161/714 (22.55%)
Blood and lymphatic system disorders
Anaemia ^* 1	2/356 (0.56%)	4	5/358 (1.40%)	6	7/714 (0.98%)	10
Febrile neutropenia ^* 1	5/356 (1.40%)	7	7/358 (1.96%)	7	12/714 (1.68%)	14
Leukopenia ^* 1	2/356 (0.56%)	3	0/358 (0.00%)	0	2/714 (0.28%)	3
Neutropenia ^* 1	4/356 (1.12%)	5	6/358 (1.68%)	8	10/714 (1.40%)	13
Pancytopenia ^* 1	1/356 (0.28%)	2	1/358 (0.28%)	1	2/714 (0.28%)	3
Thrombocytopenia ^* 1	3/356 (0.84%)	5	3/358 (0.84%)	3	6/714 (0.84%)	8
Cardiac disorders
Acute coronary syndrome ^* 1	1/356 (0.28%)	1	1/358 (0.28%)	1	2/714 (0.28%)	2
Acute myocardial infarction ^* 1	1/356 (0.28%)	1	1/358 (0.28%)	1	2/714 (0.28%)	2
Angina unstable ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Cardiac arrest ^* 1	1/356 (0.28%)	1	1/358 (0.28%)	1	2/714 (0.28%)	2
Cardiac failure ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Cardio-respiratory arrest ^* 1	0/356 (0.00%)	0	2/358 (0.56%)	2	2/714 (0.28%)	2
Cardiovascular insufficiency ^* 1	1/356 (0.28%)	1	1/358 (0.28%)	1	2/714 (0.28%)	2
Myocardial infarction ^* 1	1/356 (0.28%)	1	1/358 (0.28%)	1	2/714 (0.28%)	2
Right ventricular failure ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Gastrointestinal disorders
Abdominal pain ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Colitis ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Colitis ischaemic ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Constipation ^* 1	0/356 (0.00%)	0	2/358 (0.56%)	2	2/714 (0.28%)	2
Diarrhoea ^* 1	2/356 (0.56%)	3	2/358 (0.56%)	3	4/714 (0.56%)	6
Enterocolitis ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Faecaloma ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Gastritis ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Haemorrhoidal haemorrhage ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Ileus ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Intestinal obstruction ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Nausea ^* 1	0/356 (0.00%)	0	2/358 (0.56%)	2	2/714 (0.28%)	2
Neutropenic colitis ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Peptic ulcer ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Rectal haemorrhage ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Small intestinal perforation ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Subileus ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Vomiting ^* 1	1/356 (0.28%)	1	1/358 (0.28%)	1	2/714 (0.28%)	2
General disorders
Asthenia ^* 1	4/356 (1.12%)	5	1/358 (0.28%)	1	5/714 (0.70%)	6
Chest pain ^* 1	1/356 (0.28%)	1	1/358 (0.28%)	1	2/714 (0.28%)	2
Death ^* 1	2/356 (0.56%)	2	3/358 (0.84%)	3	5/714 (0.70%)	5
Disease progression ^* 1	4/356 (1.12%)	4	5/358 (1.40%)	5	9/714 (1.26%)	9
General physical health deterioration ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Pain ^* 1	2/356 (0.56%)	2	1/358 (0.28%)	1	3/714 (0.42%)	3
Hepatobiliary disorders
Cholangitis acute ^* 1	2/356 (0.56%)	2	0/358 (0.00%)	0	2/714 (0.28%)	2
Cholelithiasis ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Immune system disorders
Anaphylactic reaction ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Infections and infestations
Anal infection ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Appendicitis perforated ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Bacteraemia ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Disseminated tuberculosis ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Enterocolitis infectious ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Febrile infection ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Gastroenteritis ^* 1	4/356 (1.12%)	4	0/358 (0.00%)	0	4/714 (0.56%)	4
Infection ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Infectious pleural effusion ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Lower respiratory tract infection ^* 1	1/356 (0.28%)	1	2/358 (0.56%)	2	3/714 (0.42%)	3
Lung abscess ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Lung infection ^* 1	1/356 (0.28%)	1	1/358 (0.28%)	1	2/714 (0.28%)	2
Oral fungal infection ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Pleural infection ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Pneumonia ^* 1	8/356 (2.25%)	11	6/358 (1.68%)	6	14/714 (1.96%)	17
Respiratory tract infection ^* 1	2/356 (0.56%)	2	0/358 (0.00%)	0	2/714 (0.28%)	2
Sepsis ^* 1	0/356 (0.00%)	0	2/358 (0.56%)	2	2/714 (0.28%)	2
Septic shock ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Sinusitis ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Soft tissue infection ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Urinary tract infection ^* 1	1/356 (0.28%)	1	2/358 (0.56%)	3	3/714 (0.42%)	4
Injury, poisoning and procedural complications
Femur fracture ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Fracture ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Infusion related reaction ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Subarachnoid haemorrhage ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	2	1/714 (0.14%)	2
Investigations
Alanine aminotransferase increased ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Blood bilirubin increased ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Neutrophil count decreased ^* 1	1/356 (0.28%)	1	1/358 (0.28%)	1	2/714 (0.28%)	2
Metabolism and nutrition disorders
Decreased appetite ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Dehydration ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Hypercalcaemia ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Hyperkalaemia ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Hyponatraemia ^* 1	4/356 (1.12%)	5	0/358 (0.00%)	0	4/714 (0.56%)	5
Musculoskeletal and connective tissue disorders
Bone pain ^* 1	0/356 (0.00%)	0	2/358 (0.56%)	2	2/714 (0.28%)	2
Myalgia ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bone cancer metastatic ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Neoplasm progression ^* 1	2/356 (0.56%)	3	2/358 (0.56%)	2	4/714 (0.56%)	5
Tumour necrosis ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Nervous system disorders
Cerebral haemorrhage ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Cerebral ischaemia ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Dizziness ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Haemorrhagic stroke ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Headache ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Ischaemic stroke ^* 1	0/356 (0.00%)	0	3/358 (0.84%)	4	3/714 (0.42%)	4
Mononeuropathy ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Paraesthesia ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Renal and urinary disorders
Proteinuria ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Renal cyst ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Urinary retention ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Chronic obstructive pulmonary disease ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Cough ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Dyspnoea ^* 1	2/356 (0.56%)	2	2/358 (0.56%)	2	4/714 (0.56%)	4
Epistaxis ^* 1	2/356 (0.56%)	2	1/358 (0.28%)	2	3/714 (0.42%)	4
Haemoptysis ^* 1	2/356 (0.56%)	2	2/358 (0.56%)	3	4/714 (0.56%)	5
Pneumonitis ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Pneumothorax ^* 1	2/356 (0.56%)	2	1/358 (0.28%)	1	3/714 (0.42%)	3
Pulmonary embolism ^* 1	7/356 (1.97%)	7	2/358 (0.56%)	2	9/714 (1.26%)	9
Pulmonary haemorrhage ^* 1	3/356 (0.84%)	3	3/358 (0.84%)	3	6/714 (0.84%)	6
Pulmonary oedema ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Respiratory failure ^* 1	1/356 (0.28%)	2	0/358 (0.00%)	0	1/714 (0.14%)	2
Vascular disorders
Brachiocephalic vein thrombosis ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Embolism arterial ^* 1	1/356 (0.28%)	1	1/358 (0.28%)	1	2/714 (0.28%)	2
Haemorrhage ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Hypertensive crisis ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Ischaemia ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
Shock haemorrhagic ^* 1	0/356 (0.00%)	0	1/358 (0.28%)	1	1/714 (0.14%)	1
Subgaleal haematoma ^* 1	1/356 (0.28%)	1	0/358 (0.00%)	0	1/714 (0.14%)	1
1 Term from vocabulary, MedDRA 20.1 * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	PF-06439535		Bevacizumab-EU		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	328/356 (92.13%)		333/358 (93.02%)		661/714 (92.58%)
Blood and lymphatic system disorders
Leukopenia ^* 1	26/356 (7.30%)	44	30/358 (8.38%)	56	56/714 (7.84%)	100
Neutropenia ^* 1	59/356 (16.57%)	130	66/358 (18.44%)	144	125/714 (17.51%)	274
Thrombocytopenia ^* 1	55/356 (15.45%)	122	66/358 (18.44%)	125	121/714 (16.95%)	247
Anaemia ^* 1	102/356 (28.65%)	196	106/358 (29.61%)	200	208/714 (29.13%)	396
Gastrointestinal disorders
Constipation ^* 1	39/356 (10.96%)	45	27/358 (7.54%)	36	66/714 (9.24%)	81
Diarrhoea ^* 1	46/356 (12.92%)	59	48/358 (13.41%)	66	94/714 (13.17%)	125
Nausea ^* 1	71/356 (19.94%)	111	69/358 (19.27%)	112	140/714 (19.61%)	223
Vomiting ^* 1	41/356 (11.52%)	52	33/358 (9.22%)	42	74/714 (10.36%)	94
General disorders
Asthenia ^* 1	46/356 (12.92%)	78	43/358 (12.01%)	65	89/714 (12.46%)	143
Fatigue ^* 1	73/356 (20.51%)	110	71/358 (19.83%)	87	144/714 (20.17%)	197
Pyrexia ^* 1	24/356 (6.74%)	31	23/358 (6.42%)	41	47/714 (6.58%)	72
Injury, poisoning and procedural complications
Infusion related reaction ^* 1	19/356 (5.34%)	26	22/358 (6.15%)	26	41/714 (5.74%)	52
Investigations
Alanine aminotransferase increased ^* 1	49/356 (13.76%)	95	39/358 (10.89%)	53	88/714 (12.32%)	148
Aspartate aminotransferase increased ^* 1	44/356 (12.36%)	94	37/358 (10.34%)	59	81/714 (11.34%)	153
Blood alkaline phosphatase increased ^* 1	29/356 (8.15%)	46	32/358 (8.94%)	48	61/714 (8.54%)	94
Blood creatinine increased ^* 1	16/356 (4.49%)	28	21/358 (5.87%)	33	37/714 (5.18%)	61
Platelet count decreased ^* 1	23/356 (6.46%)	31	19/358 (5.31%)	38	42/714 (5.88%)	69
Weight decreased ^* 1	36/356 (10.11%)	43	29/358 (8.10%)	40	65/714 (9.10%)	83
Metabolism and nutrition disorders
Decreased appetite ^* 1	48/356 (13.48%)	76	46/358 (12.85%)	65	94/714 (13.17%)	141
Musculoskeletal and connective tissue disorders
Arthralgia ^* 1	40/356 (11.24%)	82	43/358 (12.01%)	71	83/714 (11.62%)	153
Bone pain ^* 1	25/356 (7.02%)	58	23/358 (6.42%)	47	48/714 (6.72%)	105
Myalgia ^* 1	54/356 (15.17%)	131	49/358 (13.69%)	109	103/714 (14.43%)	240
Pain in extremity ^* 1	16/356 (4.49%)	23	23/358 (6.42%)	29	39/714 (5.46%)	52
Nervous system disorders
Headache ^* 1	30/356 (8.43%)	35	37/358 (10.34%)	45	67/714 (9.38%)	80
Neuropathy peripheral ^* 1	53/356 (14.89%)	67	65/358 (18.16%)	86	118/714 (16.53%)	153
Paraesthesia ^* 1	40/356 (11.24%)	64	31/358 (8.66%)	36	71/714 (9.94%)	100
Peripheral sensory neuropathy ^* 1	34/356 (9.55%)	45	46/358 (12.85%)	70	80/714 (11.20%)	115
Polyneuropathy ^* 1	23/356 (6.46%)	34	19/358 (5.31%)	22	42/714 (5.88%)	56
Renal and urinary disorders
Proteinuria ^* 1	28/356 (7.87%)	50	34/358 (9.50%)	76	62/714 (8.68%)	126
Respiratory, thoracic and mediastinal disorders
Cough ^* 1	41/356 (11.52%)	53	47/358 (13.13%)	58	88/714 (12.32%)	111
Dyspnoea ^* 1	32/356 (8.99%)	38	35/358 (9.78%)	41	67/714 (9.38%)	79
Epistaxis ^* 1	40/356 (11.24%)	51	32/358 (8.94%)	48	72/714 (10.08%)	99
Skin and subcutaneous tissue disorders
Alopecia ^* 1	166/356 (46.63%)	216	165/358 (46.09%)	232	331/714 (46.36%)	448
Rash ^* 1	9/356 (2.53%)	10	21/358 (5.87%)	29	30/714 (4.20%)	39
Vascular disorders
Hypertension ^* 1	60/356 (16.85%)	83	62/358 (17.32%)	110	122/714 (17.09%)	193
1 Term from vocabulary, MedDRA 20.1 * Indicates events were collected by non-systematic assessment

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.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Results Point of Contact

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Name/Title:	Pfizer ClinicalTrials.gov Call Center
Organization:	Pfizer, Inc.
Phone:	1-800-718-1021
EMail:	ClinicalTrials.gov_Inquiries@pfizer.com

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

Li CSW, Sweeney K, Cronenberger C. Population pharmacokinetic modeling of PF-06439535 (a bevacizumab biosimilar) and reference bevacizumab (Avastin(R)) in patients with advanced non-squamous non-small cell lung cancer. Cancer Chemother Pharmacol. 2020 Mar;85(3):487-499. doi: 10.1007/s00280-019-03946-8. Epub 2019 Nov 26.

Reinmuth N, Bryl M, Bondarenko I, Syrigos K, Vladimirov V, Zereu M, Bair AH, Hilton F, Liau K, Kasahara K. PF-06439535 (a Bevacizumab Biosimilar) Compared with Reference Bevacizumab (Avastin(R)), Both Plus Paclitaxel and Carboplatin, as First-Line Treatment for Advanced Non-Squamous Non-Small-Cell Lung Cancer: A Randomized, Double-Blind Study. BioDrugs. 2019 Oct;33(5):555-570. doi: 10.1007/s40259-019-00363-4.

Layout table for additonal information

Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT02364999
Other Study ID Numbers:	B7391003 2014-003878-16 ( EudraCT Number ) B7391003 ( Other Identifier: Alias Study Number )
First Submitted:	February 10, 2015
First Posted:	February 18, 2015
Results First Submitted:	May 7, 2018
Results First Posted:	June 27, 2018
Last Update Posted:	February 7, 2019

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