Margetuximab Plus Chemotherapy vs Trastuzumab Plus Chemotherapy in the Treatment of HER2+ Metastatic Breast Cancer

NCT ID: NCT02492711

Last Updated: 2025-03-17

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

624 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-08-24

Study Completion Date

2022-06-14

Brief Summary

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The purpose of this study is to determine whether patients with metastatic breast cancer treated with margetuximab plus chemotherapy have longer progression free survival (PFS) and overall survival (OS) than patients treated with trastuzumab plus chemotherapy.

A non-randomized sub-study cohort of approximately 88 patients will be enrolled to evaluate the safety of a reduced margetuximab infusion rate in patients receiving margetuximab either as monotherapy or in combination with chemotherapy.

Detailed Description

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Conditions

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HER-2 Positive Breast Cancer Metastatic Neoplasm

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Margetuximab plus chemotherapy

Margetuximab 15 mg/kg every 21 days

Group Type EXPERIMENTAL

Margetuximab

Intervention Type BIOLOGICAL

15 mg/kg via IV (intravenous) infusion on day 1 of each 21 day cycle,

Physician's choice of chemotherapy.

Intervention Type DRUG

Capecitabine (Xeloda®):1000 mg/m2 BID for 14 days in a 21-day cycle, or Eribulin (Halaven®): 1.4 mg/m2 on days 1 and 8 of a 21-day cycle, or Gemcitabine (Gemzar®): 1000 mg/m2 on days 1 and 8 of a 21-day cycle, or Vinorelbine (Navelbine®): 25-30 mg/m2 on days 1 and 8 of a 21-day cycle

Trastuzumab plus chemotherapy

Trastuzumab 8 mg/kg loading dose, then 6 mg/kg every 21 days

Group Type ACTIVE_COMPARATOR

Trastuzumab

Intervention Type BIOLOGICAL

8 mg/kg via IV (intravenous) infusion for the first dose and 6 mg/kg for all subsequent doses via IV infusion on day 1 of each 21 day cycle

Physician's choice of chemotherapy.

Intervention Type DRUG

Capecitabine (Xeloda®):1000 mg/m2 BID for 14 days in a 21-day cycle, or Eribulin (Halaven®): 1.4 mg/m2 on days 1 and 8 of a 21-day cycle, or Gemcitabine (Gemzar®): 1000 mg/m2 on days 1 and 8 of a 21-day cycle, or Vinorelbine (Navelbine®): 25-30 mg/m2 on days 1 and 8 of a 21-day cycle

Margetuximab Infusion Sub-study

Margetuximab 15 mg/kg every 21 days (with or without chemotherapy), studying a shorter duration of infusion beginning in Cycle 2.

Group Type EXPERIMENTAL

Margetuximab

Intervention Type BIOLOGICAL

15 mg/kg via IV (intravenous) infusion on day 1 of each 21 day cycle,

Physician's choice of chemotherapy.

Intervention Type DRUG

Capecitabine (Xeloda®):1000 mg/m2 BID for 14 days in a 21-day cycle, or Eribulin (Halaven®): 1.4 mg/m2 on days 1 and 8 of a 21-day cycle, or Gemcitabine (Gemzar®): 1000 mg/m2 on days 1 and 8 of a 21-day cycle, or Vinorelbine (Navelbine®): 25-30 mg/m2 on days 1 and 8 of a 21-day cycle

Interventions

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Margetuximab

15 mg/kg via IV (intravenous) infusion on day 1 of each 21 day cycle,

Intervention Type BIOLOGICAL

Trastuzumab

8 mg/kg via IV (intravenous) infusion for the first dose and 6 mg/kg for all subsequent doses via IV infusion on day 1 of each 21 day cycle

Intervention Type BIOLOGICAL

Physician's choice of chemotherapy.

Capecitabine (Xeloda®):1000 mg/m2 BID for 14 days in a 21-day cycle, or Eribulin (Halaven®): 1.4 mg/m2 on days 1 and 8 of a 21-day cycle, or Gemcitabine (Gemzar®): 1000 mg/m2 on days 1 and 8 of a 21-day cycle, or Vinorelbine (Navelbine®): 25-30 mg/m2 on days 1 and 8 of a 21-day cycle

Intervention Type DRUG

Other Intervention Names

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MGAH22 Margenza® Herceptin®

Eligibility Criteria

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Inclusion Criteria

* Histologically-proven metastatic or locally-advanced relapsed/refractory HER2+ breast cancer based on the most recently available tumor biopsy collected from the patient. Tumors may be estrogen receptor (ER)/progesterone receptor (PgR) positive or negative.
* Have received at least 2 prior lines of anti-HER2 directed therapy in the metastatic setting, or in case of having received (neo)adjuvant pertuzumab, at least 1 prior line of anti-HER2 directed therapy in the metastatic setting. In either case, patients must have received prior treatment with pertuzumab, in the (neo)adjuvant or metastatic setting. Prior radiotherapy, hormonal therapies, and other anti-HER2 therapies are allowed.
* Prior treatment with at least one, and no more than three, lines of therapy overall in the metastatic setting. Patients must have progressed on or following, the most recent line of therapy.
* Resolution of all chemotherapy or radiation-related toxicities to ≤ Grade 1
* Life expectancy ≥ 12 weeks
* Acceptable laboratory parameters
* Women of childbearing potential must have negative pregnancy test performed within 14 days of randomization and on the first day of treatment. All subjects must agree to use an effective form of contraception for the duration of study treatment and for 7 months after the last dose of study drug.

Infusion sub-study prior therapy requirements: Same as above, except:

* Must have received 4 or more prior lines or therapy in the metastatic setting
* Must have received prior trastuzumab, pertuzumab, and T-DM1

Exclusion Criteria

* Known, untreated brain metastasis. Patients with signs or symptoms of brain metastasis must have a CT or MRI performed within 4 weeks prior to randomization to specifically exclude the presence of radiographically-detected brain metastases
* History of uncontrolled seizures within 6 months of randomization
* History of prior allogeneic bone marrow, stem-cell, or solid organ transplantation
* History of clinically significant cardiovascular disease
* Clinically-significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation
* Any condition that would be a contraindication to receiving trastuzumab as described in the approved local label or a condition that would prevent treatment with the physician's choice of chemotherapy
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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MacroGenics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Ironwood Cancer & Research Center

Chandler, Arizona, United States

Site Status

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Site Status

Western Regional Medical Center, Inc.

Goodyear, Arizona, United States

Site Status

East Valley Hematology And Oncology

Burbank, California, United States

Site Status

UCLA Hematology Oncology Santa Monica

Los Angeles, California, United States

Site Status

UC Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

Sharp Memorial Hospital

San Diego, California, United States

Site Status

University of California, San Francisco Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Kaiser Permenente Medical Center

Vallejo, California, United States

Site Status

Poudre Valley Health Care, Inc.

Fort Collins, Colorado, United States

Site Status

MedStar Washington Hospital Center

Washington D.C., District of Columbia, United States

Site Status

Florida Cancer Specialists

Fort Myers, Florida, United States

Site Status

Memorial Cancer Institute at Memorial Regional Hospital

Hollywood, Florida, United States

Site Status

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, United States

Site Status

Florida Cancer Specialists

New Port Richey, Florida, United States

Site Status

Orlndo Health Cancer Center

Orlando, Florida, United States

Site Status

Hem-Onc Associates

Port Saint Lucie, Florida, United States

Site Status

Palm Beach Cancer Center

West Palm Beach, Florida, United States

Site Status

Piedmont Cancer Institute, P.C.

Atlanta, Georgia, United States

Site Status

Northwest Georgia Oncology Centers, PC

Marietta, Georgia, United States

Site Status

CTCA - Southeastern Regional Medical Center

Newnan, Georgia, United States

Site Status

Kaiser Permanente Hawaii Moanalua Medical Center

Honolulu, Hawaii, United States

Site Status

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Carle Cancer Center

Urbana, Illinois, United States

Site Status

CTCA - Midwestern Regional Medical Center

Zion, Illinois, United States

Site Status

Indiana University Health Goshen Center for Cancer Care

Goshen, Indiana, United States

Site Status

ARH Cancer Clinic

Hazard, Kentucky, United States

Site Status

St. Joseph's Hospital

Lexington, Kentucky, United States

Site Status

Touro Infirmary Hospital

New Orleans, Louisiana, United States

Site Status

New England Cancer Specialists

Scarborough, Maine, United States

Site Status

Mercy Medical Center

Baltimore, Maryland, United States

Site Status

Tufts-NEMC Cancer Center

Boston, Massachusetts, United States

Site Status

Forrest General Hospital

Hattiesburg, Mississippi, United States

Site Status

Saint Luke's Cancer Specialists

Kansas City, Missouri, United States

Site Status

Mercy Hospital Saint Louis

St Louis, Missouri, United States

Site Status

Dartmouth-Hitchcock - Norris C

Lebanon, New Hampshire, United States

Site Status

New Jersey Hematology Oncology Associates

Brick, New Jersey, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Saint Barnabas Medical Center - The Cancer Center

Livingston, New Jersey, United States

Site Status

New Mexico Cancer Care Alliance (NMCCA)

Albuquerque, New Mexico, United States

Site Status

Queens Hospital Center

Jamaica, New York, United States

Site Status

ProHEALTH CARE Associates, LLP

Lake Success, New York, United States

Site Status

New York University Clinical Cancer Center

New York, New York, United States

Site Status

Wake Forest University Baptist Medical Center (WFUBMC)

Winston-Salem, North Carolina, United States

Site Status

Mercy Physicians Of Oklahoma

Oklahoma City, Oklahoma, United States

Site Status

Pinnacle Health Cancer Institute

Harrisburg, Pennsylvania, United States

Site Status

Monongahela Valley Hospital

Monongahela, Pennsylvania, United States

Site Status

CTCA - Eastern Regional Medical Center, Inc.

Philadelphia, Pennsylvania, United States

Site Status

Guthrie Medical Group, PC

Sayre, Pennsylvania, United States

Site Status

Tennessee Oncology, PLLC

Chattanooga, Tennessee, United States

Site Status

The Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Austin Cancer Center

Austin, Texas, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

The Center for Cancer and Blood Disorders

Fort Worth, Texas, United States

Site Status

Utah Cancer Specialists

Salt Lake City, Utah, United States

Site Status

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Site Status

Inova Schar Cancer Institute

Fairfax, Virginia, United States

Site Status

Fort Belvoir Community Hospital

Fort Belvoir, Virginia, United States

Site Status

Swedish Cancer Institute/ Swedish Health Services

Seattle, Washington, United States

Site Status

University of Washington/ Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

Cancer Care Northwest, PS

Spokane, Washington, United States

Site Status

Medizinische Universität Innsbruck

Innsbruck, Tyrol, Austria

Site Status

UZ Antwerpen

Edegem, Antwerpen, Belgium

Site Status

GZA Ziekenhuizen - Campus Sint-Augustinus

Wilrijk, Antwerpen, Belgium

Site Status

Clinique Saint-Pierre Ottignies

Ottignies, Brabant Wallon, Belgium

Site Status

UZ Brussel - Campus Jette

Brussels, Brussels Capital, Belgium

Site Status

Cliniques universitaires Saint-Luc

Brussels, Brussels Capital, Belgium

Site Status

Jessa Ziekenhuis - Campus Virga Jesse

Hasselt, Limburg, Belgium

Site Status

AZ Nikolaas - Campus Sint-Niklaas Moerland

Sint-Niklaas, Oost-Vlaanderen, Belgium

Site Status

AZ Sint-Jan Brugge - Oostende - Campus Sint-Jan

Bruges, West-Vlaanderen, Belgium

Site Status

AZ Groeninge - Campus Loofstraat

Kortrijk, West-Vlaanderen, Belgium

Site Status

AZ Damiaan

Ostend, West-Vlaanderen, Belgium

Site Status

Chc - Clinique Saint-Joseph

Liège, , Belgium

Site Status

Clinique Sainte Elisabeth

Namur, , Belgium

Site Status

Dr. Leon Richard Oncology Centre

Moncton, New Brunswick, Canada

Site Status

Lakeridge Health Oshawa

Oshawa, Ontario, Canada

Site Status

Masarykuv onkologicky ustav

Brno, Brno-město, Czechia

Site Status

Fakultni nemocnice Olomouc

Olomouc, , Czechia

Site Status

Fakultni nemocnice v Motole

Prague, , Czechia

Site Status

Aarhus Universitetshospital

Aarhus C, Central Jutland, Denmark

Site Status

Regionshospitalet Herning (Herning Centralsygehus)

Herning, Central Jutland, Denmark

Site Status

Vejle Sygehus

Vejle, Region Syddanmark, Denmark

Site Status

Næstved Sygehus

Aarhus N, Zeeland, Denmark

Site Status

Tampere University Hospital

Tampere, Etelä-Suomen Lääni, Finland

Site Status

Helsinki University Central Hospital (HUCH) - Meilahden Sair

Helsinki, Länsi-Suomen Lääni, Finland

Site Status

Center de Lutte Contre le Cancer (CLCC)

Nice, Alpes-Martitimes, France

Site Status

Centre Léon Bérard

Lyon, Auvergne-Rhône-Alpes, France

Site Status

Center de Lutte Contre le Cancer (CLCC)

Caen, Calvados, France

Site Status

Centre Georges-François Lecler

Dijon, Côte-d'Or, France

Site Status

Centre de Lutte Contre le Cancer (CLCC) - Institut de Cancer

Saint-Herblain, Loire-Atlantique, France

Site Status

Centre Jean Perrin

Clermont-Ferrand, Puy-de-Dôme, France

Site Status

Institut Curie

Paris, Île-de-France Region, France

Site Status

Institut Curie - Hôpital René Huguenin

Saint-Cloud, Île-de-France Region, France

Site Status

Universitaetsklinikum Tuebingen

Tübingen, Baden-Wurttemberg, Germany

Site Status

Universitätsklinikum Erlangen

Erlangen, Bavaria, Germany

Site Status

Praxis für Frauenheilkunde Anita

München, Bavaria, Germany

Site Status

Marien Hospital Düsseldorf

Düsseldorf, Nordhein-Westfalen, Germany

Site Status

Universitaetsklinikum Essen - Klinik fuer Frauenheilkunde

Essen, North Rhine-Westphalia, Germany

Site Status

Marien Hospital

Witten, North Rhine-Westphalia, Germany

Site Status

Medizinische Fakultät Carl Gustav Carus

Dresden, Saxony, Germany

Site Status

Universtatsklinikum Heidelberg Nationales

Heidelberg, , Germany

Site Status

Meir Medical Center

Kfar Saba, Central District, Israel

Site Status

Rabin Medical Center - Beilinson Hospital

Petah Tikva, Central District, Israel

Site Status

The Chaim Sheba Medical Center - Insititute of Oncology

Ramat Gan, Central District, Israel

Site Status

Kaplan Medical Center

Rehovot, Central District, Israel

Site Status

Hadassah Medical Organisation, Hadassah Medical Center, Ein-Karem

Jerusalem, Jerusalem, Israel

Site Status

Soroka Medical Center [Oncology]

Beersheba, Southern District, Israel

Site Status

Clalit Health Services - Lin Medical Center

Haifa, , Israel

Site Status

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

PO Garibaldi-Nesima, ARNAS Garibaldi

Catania, Cantania, Italy

Site Status

Irccs Irst

Meldola, Forli, Italy

Site Status

Istituto di Candiolo, IRCCS

Candiolo, Torino, Italy

Site Status

Azienda Ospedaliero Universitaria Senese Universita degli St

Siena, Tuscany, Italy

Site Status

Ospedale Umberto I, AOU Ospedali Riuniti Umberto I - GM.Lanc

Ancona, , Italy

Site Status

AO G.Rummo

Benevento, , Italy

Site Status

ASST Papa Giovanni XXIII - Oncologia-Bergamo

Bergamo, , Italy

Site Status

PO di Cremona, ASST di Cremona - Patologia Mammaria e Breast Unit - Cremona

Cremona, , Italy

Site Status

Arcispedale S.Anna, AOU di Ferrara

Ferrara, , Italy

Site Status

E.O. Ospedali Galliera

Genova, , Italy

Site Status

PO A.Manzoni di Lecco, ASST Lecco - Oncologia Medica - Lecco

Lecco, , Italy

Site Status

Azienda Ospedaliera Fatebenefratelli e Oftalmico

Milan, , Italy

Site Status

Istituto Europeo di Oncologia Via Ripamonti

Milan, , Italy

Site Status

AOU Policlinico di Modena

Modena, , Italy

Site Status

Fondazione Pascale, IRCCS Istituto Nazionale dei Tumori

Napoli, , Italy

Site Status

AOU di Parma

Parma, , Italy

Site Status

IRCCS Policlinico San Matteo

Pavia, , Italy

Site Status

IRCSS Fodazione Salvatore Maugeri

Pavia, , Italy

Site Status

SO S.Chiara, AOU Pisana

Pisa, , Italy

Site Status

Nuovo ospedale di Prato

Prato, , Italy

Site Status

PU Campus Bio-medico di Roma

Roma, , Italy

Site Status

AO S.Andrea, Università degli Studi di Roma La Sapienza

Roma, , Italy

Site Status

Ospedale Belcolle Viterbo

Viterbo, , Italy

Site Status

Maastricht University Medical Centre

Maastricht, Limburg, Netherlands

Site Status

Haga Ziekenhuis, loc. Leyenburg

The Hague, South Holland, Netherlands

Site Status

MAGODENT Sp. z o.o.

Warsaw, Masovian Voivodeship, Poland

Site Status

Mazowiecki Szpital Onkologiczny

Wieliszew, Masovian Voivodeship, Poland

Site Status

Centrum Onkologii Ziemi Lubelskiej im. Sw. Jana z Dukli

Lublin, , Poland

Site Status

Centro Clínico Champalimaud/Fundação Champalimaud

Lisbon, Lisbon District, Portugal

Site Status

H. Santa Maria - Centro Hospitalar Lisboa Norte

Lisbon, , Portugal

Site Status

Instituto Português Oncologia Francisco Gentil do Porto

Porto, , Portugal

Site Status

Fundacion de Investigacion de Diego

San Juan, , Puerto Rico

Site Status

Seoul National University Hospital

Seoul, Seoul Teugbyeolsi, South Korea

Site Status

Severance Hospital, Yonsei University Health System

Seoul, Seoul Teugbyeolsi, South Korea

Site Status

Asan Medical Center

Seoul, Seoul Teugbyeolsi, South Korea

Site Status

Samsung Medical Center

Seoul, Seoul Teugbyeolsi, South Korea

Site Status

H.U.V. del Rocío

Seville, Andalusia, Spain

Site Status

Institut Català d'Oncologia-Hospital Germans Trias i Pujol

Badalona, Barcelona, Spain

Site Status

Hospital Universitari Parc Taulí

Sabadell, Barcelona, Spain

Site Status

Hospital del Mar

Barcelona, Catalonia, Spain

Site Status

H.C.U. Valencia

Valencia, Comunidad, Spain

Site Status

Hospital de Navarra

Pamplona, Navarre, Spain

Site Status

H.U. Sant Joan de Reus

Reus, Tarragona, Spain

Site Status

Hospital Ntra. Sra. de Sonsoles

Ávila, , Spain

Site Status

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Site Status

H. San Pedro de Alcántara

Cáceres, , Spain

Site Status

H.U. Arnau de Vilanova

Lleida, , Spain

Site Status

M.D. Anderson Cancer Center Madrid

Madrid, , Spain

Site Status

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Site Status

Hospital Universitario Clínico San Carlos

Madrid, , Spain

Site Status

Fundación Instituto Valenciano de Oncología

Valencia, , Spain

Site Status

Hospital Universitari I Politecnic La Fe

Valencia, , Spain

Site Status

Guys and St Thomas Hospital

London, City of London, United Kingdom

Site Status

Castle Hill Hospital (Hull)

Hull, East Riding Of Yorkshire, United Kingdom

Site Status

Kent Oncology Centre, Maidstone Hospital

Maidstone, Kent, United Kingdom

Site Status

Royal Preston Hospital

Fulwood, Lancashire, United Kingdom

Site Status

South Tees Hospitals NHS Foundation Trust

Middlesbrough, , United Kingdom

Site Status

Countries

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United States Austria Belgium Canada Czechia Denmark Finland France Germany Israel Italy Netherlands Poland Portugal Puerto Rico South Korea Spain United Kingdom

References

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Rugo HS, Im SA, Cardoso F, Cortes J, Curigliano G, Musolino A, Pegram MD, Bachelot T, Wright GS, Saura C, Escriva-de-Romani S, De Laurentiis M, Schwartz GN, Pluard TJ, Ricci F, Gwin WR 3rd, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petrakova K, Yardley DA, Freedman O, Jakobsen EH, Gal-Yam EN, Yerushalmi R, Fasching PA, Kaufman PA, Ashley EJ, Perez-Olle R, Hong S, Rosales MK, Gradishar WJ; SOPHIA Study Group. Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial. J Clin Oncol. 2023 Jan 10;41(2):198-205. doi: 10.1200/JCO.21.02937. Epub 2022 Nov 4.

Reference Type DERIVED
PMID: 36332179 (View on PubMed)

Rugo HS, Im SA, Cardoso F, Cortes J, Curigliano G, Musolino A, Pegram MD, Wright GS, Saura C, Escriva-de-Romani S, De Laurentiis M, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petrakova K, Yardley DA, Freedman O, Jakobsen EH, Kaufman B, Yerushalmi R, Fasching PA, Nordstrom JL, Bonvini E, Koenig S, Edlich S, Hong S, Rock EP, Gradishar WJ; SOPHIA Study Group. Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Apr 1;7(4):573-584. doi: 10.1001/jamaoncol.2020.7932.

Reference Type DERIVED
PMID: 33480963 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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CP-MGAH22-04

Identifier Type: -

Identifier Source: org_study_id

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