A Study Of PF-05280014 [Trastuzumab-Pfizer] Or Herceptin® [Trastuzumab-EU] Plus Paclitaxel In HER2 Positive First Line Metastatic Breast Cancer Treatment (REFLECTIONS B327-02)

Metastatic Breast Cancer Clinical Trial

Official title:

A PHASE 3 RANDOMIZED, DOUBLE-BLIND STUDY OF PF-05280014 PLUS PACLITAXEL VERSUS TRASTUZUMAB PLUS PACLITAXEL FOR THE FIRST-LINE TREATMENT OF PATIENTS WITH HER2-POSITIVE METASTATIC BREAST CANCER

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01989676
• Other study ID #: B3271002
• Secondary ID: REFLECTIONS B327
• Status: Completed
• Phase: Phase 3
• Start date: February 24, 2014
• Est. completion date: June 27, 2020

Study information

• Verified date: June 2021
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The current study will compare the efficacy, safety, pharmacokinetics and immunogenicity of PF-05280014 in combination with paclitaxel versus trastuzumab sourced from the European Union (trastuzumab-EU) with paclitaxel in female patients with HER2-positive, metastatic breast cancer in the first-line treatment setting. The hypothesis to be tested in this study is that the efficacy (ORR) of PF-05280014 is similar to trastuzumab-EU.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 707
• Est. completion date: June 27, 2020
• Est. primary completion date: August 24, 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed diagnosis of breast cancer.

• Presence of metastatic disease.

• Documentation of HER2 gene amplification or overexpression.

• Available tumor tissue for central review of HER2 status.

• At least 1 measurable lesion as defined by RECIST 1.1.

• Eastern Cooperative Oncology Group status of 0 to 2.

• Left ventricular ejection fraction within institutional range of normal, measured by either two dimensional echocardiogram or multigated acquisition scan.

Exclusion Criteria:

• Relapse within 1 year of last dose of previous adjuvant (including neoadjuvant) treatment (except endocrine therapy) and within 1 year before randomization.

• Prior systemic therapy for metastatic disease (except endocrine therapy).

• Prior cumulative dose of doxorubicin of >400 mg/m2, epirubicin dose >800 mg/m^2, or the equivalent dose for other anthracyclines or derivatives (eg, 72 mg/m^2 of mitoxantrone). If the patient has received more than one anthracycline, then the cumulative dose must not exceed the equivalent of 400 mg/m^2 of doxorubicin.

• Inflammatory breast cancer.

• Active uncontrolled or symptomatic central nervous system metastases.

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Biological:
• PF-05280014
Concentrate for solution for infusion, sterile vial 150 mg. Initial dose of 4 mg/kg over 90 minutes (depending on tolerability) IV infusion, then 2 mg/kg over 30 to 90 minutes (depending on tolerability) IV infusion until disease progression. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 regimen may be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.

Drug:
• Paclitaxel
A nonaqueous solution intended for dilution with a suitable parenteral fluid prior to intravenous infusion. Paclitaxel is available in 30 mg (5 mL), 100 mg (16.7 mL), and 300 mg (50 mL) multidose vials. Each mL of sterile nonpyrogenic solution contains 6 mg paclitaxel. The starting dose of paclitaxel will be 80 mg/m^2 by IV infusion over 60 minutes (duration of infusion may be modified according to local standard of care, if applicable). Provision is made for dose reduction to 70 mg/m^2 and then 60 mg/m^2 as needed. In the absence of disease progression in the judgment of the investigator or prohibitive toxicity, patients will receive treatment with paclitaxel for at least 6 cycles or until maximal benefit of response is obtained, in the judgment of the investigator.

Biological:
• Herceptin®
Concentrate for solution for infusion, sterile vial 150 mg. Initial dose of 4 mg/kg over 90 minutes (depending on tolerability) IV infusion, then 2 mg/kg over 30 to 90 minutes (depending on tolerability) IV infusion weekly until disease progression. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the Herceptin® regimen may be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.

Drug:
• Paclitaxel
A nonaqueous solution intended for dilution with a suitable parenteral fluid prior to intravenous infusion. Paclitaxel is available in 30 mg (5 mL), 100 mg (16.7 mL), and 300 mg (50 mL) multidose vials. Each mL of sterile nonpyrogenic solution contains 6 mg paclitaxel. The starting dose of paclitaxel will be 80 mg/m^2 by IV infusion over 60 minutes (duration of infusion may be modified according to local standard of care, if applicable). Provision is made for dose reduction to 70 mg/m^2 and then 60 mg/m^2 as needed. In the absence of disease progression in the judgment of the investigator or prohibitive toxicity, patients will receive treatment with paclitaxel for at least 6 cycles or until maximal benefit of response is obtained, in the judgment of the investigator.

Locations

Country	Name	City	State
Argentina	COIBA - Centro de Oncologia e Investigacion Buenos Aires	Berazategui	Buenos Aires
Argentina	Sanatorio de la Providencia	C.a.b.a
Argentina	Instituto De Oncologia De Rosario	Rosario	Santa FE
Argentina	Centro Medico San Roque	San Miguel de Tucuman	Tucuman
Brazil	Fundacao Pio XII - Hospital de Cancer de Barretos	Barretos	SAO Paulo
Brazil	Liga Paranaense de Combate ao Cancer - Hospital Erasto Gaertner	Curitiba	Parana
Brazil	Centro de Pesquisas Oncologicas de Santa Catarina - CEPON	Florianopolis	SC
Brazil	CRIO - Centro Regional Integrado de Oncologia	Fortaleza	CE
Brazil	Associacao de Combate ao Cancer em Goias - Hospital Araujo Jorge	Goiania	GO
Brazil	Associacao Hospital de Caridade Ijui	Ijui	RS
Brazil	Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral	Itajai	SC
Brazil	Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral	Itajai	Santa Catarina
Brazil	Hospital Bruno Born (Sociedade Beneficencia e Caridade de Lajeado)	Lajeado	RIO Grande DO SUL
Brazil	Instituto do Cancer de Londrina - Hospital do Cancer de Londrina - HCL	Londrina	Parana
Brazil	Centro de Pesquisa em Oncologia - Uniao Brasileira de Educacao e Assistencia	Porto Alegre	RS
Brazil	CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia - Faculdade de Medicina do ABC	Santo Andre	SP
Brazil	CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia - Faculdade de Medicina do ABC	Santo Andre	SP
Chile	Fresenius Kabi Chile Therapia iv	Santiago	RM
Chile	Administrative office	Temuco	Region DE LA Araucania
Chile	Centro de Investigacion Clinica SIM	Temuco	Region DE LA Araucania
Chile	Clinica Alemana de Temuco	Temuco	Region DE LA Araucania
Chile	Hospital Naval Almirante Nef	V Region
Chile	Instituto Oncologico Clinica Renaca	V Region
Chile	Hospital Clinico Vina Del Mar	Vina del Mar	V Region
Chile	Instituto Oncologico, Clinica Renaca	Vina del Mar	V Region
Czechia	Onkologicka klinika VFN a 1. LF UK, Fakultni poliklinika	Praha 2
Greece	General Hospital of Athens "Hippokration"	Athens
Greece	General Hospital of Chania "O Agios Georgios"	Chania	Crete
Greece	Interbalkan European Medical Center	Pylaia	Thessaloniki
Hungary	Bacs-Kiskun Megyei Korhaz, Onkoradiologiai Kozpont	Kecskemet
Hungary	Borsod-Abauj-Zemplen Megyei Korhaz, es Egyetemi Oktatokorhaz, Klinikai Onkologiai es Sugarterapias	Miskolc
Hungary	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz - Rendelointezet, Megyei Onkologiai Kozpont	Szolnok
Hungary	Markusovszky Egyetemi Oktatokorhaz	Szombathely
India	Manipal Hospital	Bengaluru	Karnataka
India	Acharya Tulsi Regional Cancer Treatment and Research Institute	Bikaner	Rajasthan
India	Acharya Harihar Regional Cancer Center	Cuttack	Odisha
India	MNJ Institute of Oncology & Regional Cancer Center	Hyderabad	Telangana
India	Meenakshi Mission Hospital and Research Centre	Madurai	Tamil NADU
India	Manipal Centre for Clinical Research	Manipal	Karnataka
India	Tata Memorial Centre, Tata Memorial Hospital	Mumbai	Maharashtra
India	Shatabdi Super Speciality Hospital	Nashik	Maharashtra
India	Advanced Centre for Treatment Research and Education in Cancer (ACTREC)	Navi Mumbai	Maharashtra
India	Deenanath Mangeshkar Hospital & Research Centre	Pune	Maharashtra
India	Sahyadri Clinical Research & Development Centre	Pune	Maharashtra
India	Sahyadri Speciality Hospital	Pune	Maharashtra
India	Department of Medicine New Block	Visakhapatnam	Andhra Pradesh
Japan	Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital	Bunkyo-ku	Tokyo
Japan	Chiba Cancer Center	Chiba
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka-Shi	Fukuoka
Japan	Hakuaikai Medical Corporation Sagara Hospital	Kagoshima
Japan	Saitama Cancer Center Hospital	Kitaadachi-gun	Saitama
Japan	Kumamoto University Hospital	Kumamoto-city	Kumamoto
Japan	Japan Community Health care Organization Kurume General Hospital	Kurume-city	Fukuoka
Japan	National Hospital Organization Tokyo Medical Center	Meguro-Ku	Tokyo
Japan	National Hospital Organization Nagoya Medical Center	Nagoya	Aichi
Japan	Niigata Cancer Center Hospital	Niigata
Japan	Nakanoshima Osaka Breast Clinic	Osaka
Japan	Osaka Breast Clinic	Osaka
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Showa University Hospital	Shinagawa-ku	Tokyo
Japan	Shizuoka General Hospital	Shizuoka
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si	Chungcheongbuk-do
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	National Cancer Centre	Goyang-si
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	Ulsan University Hospital	Ulsan	Korea
Latvia	P.Stradins Clinical University Hospital	Riga
Mexico	Consultorio dentro de la Torre Medica Dalinde (Oncologia Medica)	Mexico	Distrito Federal
Mexico	Inter Hosp S.A. de C.V. "Centro Medico Dalinde"	Mexico	Distrito Federal
Mexico	Instituto Nacional de Cancerologia	Mexico City	Distrito Federal
Mexico	Oaxaca Site Management Organization S.C.	Oaxaca
Mexico	Cancerologia de Queretaro S.C.	Queretaro
Peru	Clinica Anglo Americana	Lima
Peru	Hospital Militar Central	Lima
Peru	INNPARES	Lima
Peru	Instituto de Oncologia y Radioterapia de la Clinica Ricardo Palma	Lima
Peru	Instituto Nacional de Enfermedades Neoplasicas	Lima
Peru	Radiologos S.R.L.	Lima
Peru	Resocentro	Lima
Peru	Resocentro	Lima
Peru	Siglo XXI	Lima
Peru	Siglo XXI	Lima
Philippines	Cebu Doctors' University Hospital	Cebu City	Cebu
Philippines	The Research Institute at Perpetual Succor Hospital	Cebu City	Region VII
Philippines	Manila Doctors Hospital	Manila
Philippines	Manila Doctors Hospital	Manila	Metro Manila
Philippines	University of Philippines Manila-Philippine General Hospital	Manila	NCR
Philippines	The Medical City	Pasig City	NCR
Philippines	St. Luke's Medical Center	Quezon City	NCR
Philippines	Veterans Memorial Medical Center	Quezon City	Metro Manila
Philippines	Cardinal Santos Medical Center	San Juan City	Mentro Manila
Poland	COPERNICUS Podmiot Leczniczy Sp. z o.o. Wojewodzkie Centrum Onkologii	Gdansk
Poland	Szpitale Pomorskie Sp. z o.o. Oddzial Onkologii i Radioterapii	Gdynia
Poland	Centrum Terapii Wspolczesnej	Lodz
Poland	SPZOZ MSW z Warminsko-Mazurskim Centrum Onkologii w Olsztynie, Oddzial Kliniczny Chemioterapii	Olsztyn
Poland	MRUKMED. Lekarz Beata Madej Mruk i Partner. Sp. p. Oddzial nr 1 w Rzeszowie	Rzeszow
Poland	Magodent Sp. z o.o. Oddzial Onkologii Klinicznej/Chemioterapii	Warszawa
Portugal	Hospital de Braga	Braga
Portugal	Hospital CUF Descobertas	Lisboa
Romania	Spitalul Universitar de Urgenta, Departamentul Oncologie Medicala	Bucuresti
Romania	Institutul Oncologic Prof. Dr. Ion Chiricuta	Cluj-Napoca	Cluj
Romania	S.C. Medisprof S.R.L	Cluj-Napoca	Cluj
Romania	Centrul de Oncologie Sf. Nectarie	Craiova	Dolj
Romania	SC Oncolab SRL, Oncologie	Craiova	Jud Dolj
Romania	Spitalul Clinic Judetean de Urgenta Sibiu	Sibiu
Romania	Spitalul Judetean de Urgenta "Sf.Ioan cel Nou", Sectia Oncologie	Suceava
Romania	Spitalul Clinic Municipal de Urgenta Timisoara, Sectia Clinica Oncologie Medicala	Timisoara
Russian Federation	GBUZ Arkhangelsk Regional Clinical Oncological dispensary	Arkhangelsk
Russian Federation	State Budgetary Healthcare Institution "Chelyabinsk Regional Clinical Oncological Dispensary"	Chelyabinsk
Russian Federation	Republic Clinical Hospital of Emergency Care	Grozny	Chechenkaya Republic
Russian Federation	"Regional Budgetary Healthcare Institution ""Ivanovo Regional Oncology Dispensary"""	Ivanovo
Russian Federation	SBIH of Kaluga Region "Kaluga Regional Clinical Oncology Dispensary"	Kaluga
Russian Federation	State Healthcare Institution Kursk Regional Oncological Dispensary of the Healthcare Committee	Kislino Settlement	Kursk
Russian Federation	LLC Medekspert	Kislovodsk	Stavropol Region
Russian Federation	State Budgetary Healthcare Institution "Leningrad Regional Oncological Dispensary"	Kuzmolovo, Vsevolozhskiy	Leningrad Region
Russian Federation	Federal State Budgetary Healthcare Institution of "Clinical Hospital #101 of Federal Medical and	Lermontov	Stavropol Region
Russian Federation	GBUZ "Regional Oncology Dispensary #2"	Magnitogorsk
Russian Federation	Federal State Budgetary Institution "Russian Oncological Scientific Center n.a. N.N. Blokhin" of	Moscow
Russian Federation	FSBSI Russian Cancer Research Center n.a. N.N.Blokhin	Moscow	NAP
Russian Federation	LLC VitaMed	Moscow
Russian Federation	LLC VitaMed	Moscow
Russian Federation	State Budgetary Healthcare Institution "Nizhniy Novgorod Regional Oncological Dispensary"	Nizhniy Novgorod
Russian Federation	"BIH of Omsk Region ""Clinical oncological dispensary"""	Omsk
Russian Federation	Budgetary Institution of Healthcare of Orel region "Orel oncological dispensary"	Orel
Russian Federation	GBUZ of Perm region "Perm regional oncology dispensary"	Perm	NAP
Russian Federation	State Budgetary Healthcare Institution ''Republic Oncological Dispensary''	Petrozavodsk	Republic OF Karelia
Russian Federation	Saint-Petersburg Clinical Research Center of Specialized Types of Medical Care (Oncology)	Poselok Pesochny	Saint-petersburg
Russian Federation	Private medical institution Euromedservice	Pushkin	Saint Petersburg
Russian Federation	Centre of Specialized kinds of Medical Care of Pyatigorsk city	Pyatigorsk	Stavropol Region
Russian Federation	LLC Novaya Clinica	Pyatigorsk	Stavropol Region
Russian Federation	Pyatigorsk City Hospital #2	Pyatigorsk	Stavropol Region
Russian Federation	State Budgetary Healthcare Institution of Stavropol Region Pyatigorsk Oncology Dispensary	Pyatigorsk	Stavropol Region
Russian Federation	Stavropol Regional Hospital for War Veterans	Pyatigorsk	Stavropol Region
Russian Federation	Rostov Research Institute of Oncology	Rostov-on-Don	Rostov Region
Russian Federation	SBEI HPE RyazSMU of MoH of the Russian Federation based on SBI of Ryazan Region "Regional CLinical	Ryazan
Russian Federation	SBEI of HPE "First Saint Petersburg State Medical University	Saint Petersburg
Russian Federation	Federal State Budgetary Institution ¿National Medical Research Oncology Centre named after N.N.	Saint-Petersburg	Pos.pesochny
Russian Federation	Non-state healthcare agency Road Clinical Hospital PLC Russian Railways	Saint-Petersburg
Russian Federation	Saint-Petersburg State Budgetary Healthcare Institution "Oncological Dispensary of Moscow District"	Saint-Petersburg
Russian Federation	SBI "North-Western State Medical University n.a. I. I. Mechnikov" of the MoH of the Russian	Saint-Petersburg
Russian Federation	State budget institution of healthcare of Mordovia Republic "Republic Oncology Dispensary"	Saransk	Republic OF Mordovia
Russian Federation	Non-State Healthcare Institution "Road Clinical Hospital at Saratov II Station"	Saratov
Russian Federation	State Budgetary Healthcare Institution of Stavropol region "Stavropol regional clinical oncology	Stavropol
Russian Federation	GBUZ Republican Clinical Hospital n.a. G.F. Kuvatova	Ufa	Republic OF Baskortostan
Russian Federation	Republican Clinical Oncology Dispensary of the Ministry of Healthcare of Baskortostan Republic	Ufa	Republic OF Baskortostan
Russian Federation	State Healthcare Institution, Republican Clinical Oncology Dispensary of the Ministry of	Ufa	Republic OF Bashkortostan
Russian Federation	State Budgetary Healthcare Institution Volgograd Regional Clinical Oncology Dispensary	Volzhskiy	Volgograd Region
Serbia	Institute for Oncology and Radiology of Serbia	Belgrade
Serbia	Military Medical Academy	Belgrade
Serbia	Clinic of Oncology-Clinical Center Nis	Nis
Serbia	Oncology Institute of Vojvodina	Sremska Kamenica
Slovakia	Narodny Onkologicky Ustav	Bratislava
Slovakia	Onkologicky ustav sv. Alzbety, s.r.o.	Bratislava
South Africa	wits Clinical Research	Joannesburg	Gauteng
South Africa	Sandton Oncology Centre	Johannesburg	Gauteng
South Africa	The Medical Oncology Centre of Rosebank	Johannesburg	Gauteng
South Africa	Cape Town Oncology Trials	Kraaifontein	Western CAPE
South Africa	GVI Oncology, Langenhoven Drive Oncology Centre	Port Elizabeth	Eastern CAPE
South Africa	*Department of Medical Oncology, University of Pretoria & Steve Biko Academic Hospitals Complex	Pretoria	Gauteng
South Africa	Eastleigh Breast Care Centre	Pretoria	Gauteng
South Africa	GVI Rondebosch Oncology Centre-Rondebosch Medical Centre	Rondebosch	Western CAPE
Thailand	Udonthani Cancer Hospital	Amphur Muang	Udonthani
Thailand	Faculty of Medicine, Chulongkorn University, Medical Oncology Unit	Bangkok
Thailand	National Cancer Institute	Ratchathewi	Bangkok
Turkey	Baskent University School of Medicine Adana Hospital	Adana
Turkey	Hacettepe Universitesi Tip Fakultesi	Ankara
Turkey	Uludag Universitesi Tip Fakultesi Ic Hastaliklari Anabilim Dali	Bursa
Turkey	Dicle University Medical Faculty	Diyarbakir
Turkey	Gaziantep University Medical Faculty	Gaziantep
Turkey	Istanbul Universitesi Onkoloji Enstitusu	Istanbul
Ukraine	Municipal Institution "Chernivtsi Regional Clinical Oncology Center", Outpatient Department	Chernivtsi
Ukraine	Municipal Non-Profit Enterprise City Clinical Hospital No.4of Dnipro Regional Council, Department of	Dnipro
Ukraine	Communal Non-Profit Enterprise "Regional Center of Oncology"	Kharkiv
Ukraine	SI Institute of Medical Radiology n.a.S.P. Ilrygoriev of National Academy of Medical Science of	Kharkiv
Ukraine	Khmelnytskyi Regional Oncologic Dispensary	Khmelnytskyi
Ukraine	Municipal Enterprise 'Kryvyi Rih Oncology Dispensary of Dnipropetrovsk Regional Council'	Kryvyi Rih
Ukraine	Municipal Non-Profit Enterprise of Kyiv Regional Council "Kyiv Regional Oncology Dispensary"	Kyiv
Ukraine	Lviv State Oncologic Regional Treatment and Diagnostic Center	Lviv
Ukraine	Municipal Institution Odesa Regional Clinical Hospital, Mammology Center	Odesa
Ukraine	Zakarpattia Regional Clinical Oncological Center	Uzhgorod
Ukraine	Municipal Non-profit Enterprise Podilsk Regional Oncology Centre of Vinnytsia Regional Council	Vinnytsia
United States	Florida Cancer Research Institute	Boca Raton	Florida
United States	Cancer Center of Central Connecticut	Plainville	Connecticut
United States	Florida Cancer Research Institute	Plantation	Florida
United States	Cancer Center of Central Connecticut	Southington	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Chile,  Czechia,  Greece,  Hungary,  India,  Japan,  Korea, Republic of,  Latvia,  Mexico,  Peru,  Philippines,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  Slovakia,  South Africa,  Thailand,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) Derived From Central Radiology Assessments: ITT Population	ORR was defined as the percentage of participants who achieved complete response (CR, complete disappearance of all target lesions with the exception of nodal disease; all target nodes must have decreased to normal size [short axis <10 mm]) or partial response (PR, >=30% decrease from baseline of the sum of diameters (SOD) of all target measurable lesions; the short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions) by Week 25 of the study and confirmed on a follow-up assessment (Week 33+/-14 days), based on the assessments of the central radiology review in accordance with RECIST 1.1.	From the date of randomization until all participants had either completed the Week 33 tumor assessment or discontinued study drug earlier than the Week 33 visit
Secondary	One-year Progression-Free Survival (PFS) Rate Derived From Central Radiology Assessments: ITT Population	One-year PFS rate was analyzed based on the time from date of randomization to first documentation of progressive disease (PD), or death due to any cause in the absence of documented PD, based on the assessments of the central radiology review in accordance with RECIST 1.1. PD was defined for target disease as at least a 20% increase in sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy) with a minimum absolute increase of 5 mm. For non-target disease: PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion was also considered PD. The 95% CI for the median time to event was based on the Brookmeyer and Crowley method.	From the date of randomization until 378 days post-randomization
Secondary	Duration of Response (DOR) Per Central Radiology Assessments: ITT Population	DOR:time from first documentation of objective response (CR or PR) to first documentation of PD/death due to any cause in absence of documented PD, based on central radiology review. As per RECIST v1.1, CR:complete disappearance of all target lesions with exception of nodal disease; all target nodes reduced in short axis <10 mm. PR: >=30% decrease from baseline of SOD of target lesions; short diameter used in sum for target nodes,longest diameter used in sum for other target lesions. PD for target disease:at least 20% increase in SOD of target lesions above smallest sum observed (over baseline if no decrease in sum observed) with minimum absolute increase of 5 mm. For non-target disease:unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion was also considered PD. The 95% CI for median time to event was based on the Brookmeyer and Crowley method.	From the date of randomization until 378 days post-randomization
Secondary	Overall Survival: ITT Population	Overall survival was analyzed based on the time from date of randomization to the date of death due to any cause. Participants last known to be alive were censored on the date of last contact. The 95% CI for the median time to event was based on the Brookmeyer and Crowley Method.	From the date of randomization until end of study (approximately 6 years)
Secondary	Serum Peak Concentration of PF-05280014 at Selected Cycles: Pharmacokinetics (PK) Population	Human PK serum samples were analyzed for concentrations of PF-05280014 using a validated, sensitive, and specific enzyme-linked immunosorbent assay (ELISA).	1 hour post end of infusion on Day 1 of Cycles 1 and 5
Secondary	Serum Peak Concentration of Trastuzumab-EU at Selected Cycles: PK Population	Human PK serum samples were analyzed for concentrations of trastuzumab-EU using a validated, sensitive, and specific ELISA.	1 hour post end of infusion on Day 1 of Cycles 1 and 5
Secondary	Serum Trough (Pre-dose) Concentration of PF-05280014 at Selected Cycles: PK Population	Human PK serum samples were analyzed for concentrations of PF-05280014 using a validated, sensitive, and specific ELISA.	Pre-dose on Day 1 of Cycles 1, 3, 4, 5, 7, 8, 11, 14, 17 and Day 8 of Cycles 1 and 5
Secondary	Serum Trough (Pre-dose) Concentration of Trastuzumab-EU at Selected Cycles: PK Population	Human PK serum samples were analyzed for concentrations of trastuzumab-EU using a validated, sensitive, and specific ELISA.	Pre-dose on Day 1 of Cycles 1, 3, 4, 5, 7, 8, 11, 14, 17 and Day 8 of Cycles 1 and 5
Secondary	Number of Participants With Positive Anti-Drug Antibodies (ADA) Sample: Safety Population	Two sensitive, specific, and semi-quantitative electrochemiluminescent (ECL) immunoassays, 1 for detecting antibodies against PF-05280014 and the other for detecting antibodies against trastuzumab, were used to analyze ADA samples. Serum samples were first screened for ADA. Any samples that were positive in the screening assay were further analyzed to confirm the positive result and determine the antibody titers. All samples were taken prior to dosing. The number of participants with a positive sample (titer >=1.0) is provided.	Pre-dose on Day 1 of Cycles 1, 3, 5, 8, 11, 14, 17
Secondary	Number of Participants With Positive Neutralizing Antibodies (Nab) Prior to Treatment: Safety Population	Human serum samples testing positive for the presence of ADA (anti-PF-05280014 or anti-trastuzumab-EU) were analyzed for the presence or absence of NAb (neutralizing anti-PF-05280014 or neutralizing anti-trastuzumab-EU antibodies) following a tiered approach using screening and titer determination. The number of participants at baseline (prior to treatment) with a positive NAb sample (titer >=1.48) is provided.	Cycle 1 Day 1 (prior to treatment)

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