Margetuximab Plus Chemotherapy vs Trastuzumab Plus Chemotherapy in the Treatment of HER2+ Metastatic Breast Cancer
SOPHIA
A Phase 3, Randomized Study of Margetuximab Plus Chemotherapy vs Trastuzumab Plus Chemotherapy in the Treatment of Patients With HER2+ Metastatic Breast Cancer Who Have Received Prior Anti-HER2 Therapies and Require Systemic Treatment
1 other identifier
interventional
624
18 countries
167
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Aug 2015
Longer than P75 for phase_3
167 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 6, 2015
CompletedFirst Posted
Study publicly available on registry
July 9, 2015
CompletedStudy Start
First participant enrolled
August 24, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 11, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
June 14, 2022
CompletedResults Posted
Study results publicly available
November 23, 2022
CompletedMarch 17, 2025
February 1, 2025
6 years
July 6, 2015
April 1, 2022
February 24, 2025
Conditions
Outcome Measures
Primary Outcomes (3)
Progression-free Survival (PFS) as Determined by Independent Radiological Review.
PFS is measured from the time of randomization until first documented disease progression or death from any cause, whichever is first.
Tumor assessments are conducted every 6 weeks for the first 24 weeks and then every 24 weeks until progression of cancer, average 5 months.
Overall Survival (OS) Defined as the Number of Days From Randomization to the Date of Death (From Any Cause).
Overall survival is the time from randomization until death from any cause
Throughout the study, average 21 months
Number of Patients With Grade 3 or Higher Infusion Related Reactions
Incidence of Grade 3 or higher infusion-related reactions for patients receiving 60-minute or 30-minute infusions of margetuximab in Cycle 2 of treatment
22 days
Secondary Outcomes (3)
To Evaluate Progression-free Survival (PFS), as Assessed by Study Investigators.
Tumor assessments are conducted every 6 weeks for the first 24 weeks and then every 24 weeks until progression of cancer, up to 6.5 years.
To Evaluate the Objective Response Rate (ORR) as Determined by Independent Radiological Review.
Tumor assessments are conducted every 6 weeks for the first 24 weeks and then every 24 weeks until progression of cancer, up to 6.5 years.
Infusion Rate Sub-study All Safety
Throughout the study, average duration 6 months
Study Arms (3)
Margetuximab plus chemotherapy
EXPERIMENTALMargetuximab 15 mg/kg every 21 days
Trastuzumab plus chemotherapy
ACTIVE COMPARATORTrastuzumab 8 mg/kg loading dose, then 6 mg/kg every 21 days
Margetuximab Infusion Sub-study
EXPERIMENTALMargetuximab 15 mg/kg every 21 days (with or without chemotherapy), studying a shorter duration of infusion beginning in Cycle 2.
Interventions
15 mg/kg via IV (intravenous) infusion on day 1 of each 21 day cycle,
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
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
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- MacroGenicslead
Study Sites (167)
Ironwood Cancer & Research Center
Chandler, Arizona, 85224, United States
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234, United States
Western Regional Medical Center, Inc.
Goodyear, Arizona, 85338, United States
East Valley Hematology And Oncology
Burbank, California, 91505, United States
UCLA Hematology Oncology Santa Monica
Los Angeles, California, 90095, United States
UC Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Sharp Memorial Hospital
San Diego, California, 92123, United States
University of California, San Francisco Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115, United States
Kaiser Permenente Medical Center
Vallejo, California, 94589, United States
Poudre Valley Health Care, Inc.
Fort Collins, Colorado, 80528, United States
MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20010, United States
Florida Cancer Specialists
Fort Myers, Florida, 33916, United States
Memorial Cancer Institute at Memorial Regional Hospital
Hollywood, Florida, 33021, United States
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, 33140, United States
Florida Cancer Specialists
New Port Richey, Florida, 34655, United States
Orlndo Health Cancer Center
Orlando, Florida, 32806, United States
Hem-Onc Associates
Port Saint Lucie, Florida, 34952, United States
Palm Beach Cancer Center
West Palm Beach, Florida, 33401, United States
Piedmont Cancer Institute, P.C.
Atlanta, Georgia, 30318, United States
Northwest Georgia Oncology Centers, PC
Marietta, Georgia, 30060, United States
CTCA - Southeastern Regional Medical Center
Newnan, Georgia, 30265, United States
Kaiser Permanente Hawaii Moanalua Medical Center
Honolulu, Hawaii, 96819, United States
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
Carle Cancer Center
Urbana, Illinois, 61801, United States
CTCA - Midwestern Regional Medical Center
Zion, Illinois, 60099, United States
Indiana University Health Goshen Center for Cancer Care
Goshen, Indiana, 46526, United States
ARH Cancer Clinic
Hazard, Kentucky, 41701, United States
St. Joseph's Hospital
Lexington, Kentucky, 40504, United States
Touro Infirmary Hospital
New Orleans, Louisiana, 70115, United States
New England Cancer Specialists
Scarborough, Maine, 04074, United States
Mercy Medical Center
Baltimore, Maryland, 21202, United States
Tufts-NEMC Cancer Center
Boston, Massachusetts, 02111, United States
Forrest General Hospital
Hattiesburg, Mississippi, 39401, United States
Saint Luke's Cancer Specialists
Kansas City, Missouri, 64111, United States
Mercy Hospital Saint Louis
St Louis, Missouri, 63141, United States
Dartmouth-Hitchcock - Norris C
Lebanon, New Hampshire, 03756, United States
New Jersey Hematology Oncology Associates
Brick, New Jersey, 08724, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Saint Barnabas Medical Center - The Cancer Center
Livingston, New Jersey, 07039, United States
New Mexico Cancer Care Alliance (NMCCA)
Albuquerque, New Mexico, 87106, United States
Queens Hospital Center
Jamaica, New York, 11432, United States
ProHEALTH CARE Associates, LLP
Lake Success, New York, 11042, United States
New York University Clinical Cancer Center
New York, New York, 10016, United States
Wake Forest University Baptist Medical Center (WFUBMC)
Winston-Salem, North Carolina, 27157, United States
Mercy Physicians Of Oklahoma
Oklahoma City, Oklahoma, 73120, United States
Pinnacle Health Cancer Institute
Harrisburg, Pennsylvania, 17109, United States
Monongahela Valley Hospital
Monongahela, Pennsylvania, 15063, United States
CTCA - Eastern Regional Medical Center, Inc.
Philadelphia, Pennsylvania, 19124, United States
Guthrie Medical Group, PC
Sayre, Pennsylvania, 18840, United States
Tennessee Oncology, PLLC
Chattanooga, Tennessee, 37404, United States
The Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
Austin Cancer Center
Austin, Texas, 78758, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
The Center for Cancer and Blood Disorders
Fort Worth, Texas, 76104, United States
Utah Cancer Specialists
Salt Lake City, Utah, 84106, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
Inova Schar Cancer Institute
Fairfax, Virginia, 22031, United States
Fort Belvoir Community Hospital
Fort Belvoir, Virginia, 22060, United States
Swedish Cancer Institute/ Swedish Health Services
Seattle, Washington, 98104, United States
University of Washington/ Seattle Cancer Care Alliance
Seattle, Washington, 98109, United States
Cancer Care Northwest, PS
Spokane, Washington, 99202, United States
Medizinische Universität Innsbruck
Innsbruck, Tyrol, 6020, Austria
UZ Antwerpen
Edegem, Antwerpen, 2650, Belgium
GZA Ziekenhuizen - Campus Sint-Augustinus
Wilrijk, Antwerpen, 2610, Belgium
Clinique Saint-Pierre Ottignies
Ottignies, Brabant Wallon, 1340, Belgium
UZ Brussel - Campus Jette
Brussels, Brussels Capital, 1090, Belgium
Cliniques universitaires Saint-Luc
Brussels, Brussels Capital, 1200, Belgium
Jessa Ziekenhuis - Campus Virga Jesse
Hasselt, Limburg, 3500, Belgium
AZ Nikolaas - Campus Sint-Niklaas Moerland
Sint-Niklaas, Oost-Vlaanderen, 9100, Belgium
AZ Sint-Jan Brugge - Oostende - Campus Sint-Jan
Bruges, West-Vlaanderen, 8000, Belgium
AZ Groeninge - Campus Loofstraat
Kortrijk, West-Vlaanderen, 8500, Belgium
AZ Damiaan
Ostend, West-Vlaanderen, 8400, Belgium
Chc - Clinique Saint-Joseph
Liège, 4000, Belgium
Clinique Sainte Elisabeth
Namur, 5000, Belgium
Dr. Leon Richard Oncology Centre
Moncton, New Brunswick, E1C 8X3, Canada
Lakeridge Health Oshawa
Oshawa, Ontario, L1G 2B9, Canada
Masarykuv onkologicky ustav
Brno, Brno-město, 656 53, Czechia
Fakultni nemocnice Olomouc
Olomouc, 779 00, Czechia
Fakultni nemocnice v Motole
Prague, 150 06, Czechia
Aarhus Universitetshospital
Aarhus C, Central Jutland, 8000, Denmark
Regionshospitalet Herning (Herning Centralsygehus)
Herning, Central Jutland, 7400, Denmark
Vejle Sygehus
Vejle, Region Syddanmark, 7100, Denmark
Næstved Sygehus
Aarhus N, Zeeland, 4700, Denmark
Tampere University Hospital
Tampere, Etelä-Suomen Lääni, 33521, Finland
Helsinki University Central Hospital (HUCH) - Meilahden Sair
Helsinki, Länsi-Suomen Lääni, 00029, Finland
Center de Lutte Contre le Cancer (CLCC)
Nice, Alpes-Martitimes, 06189, France
Centre Léon Bérard
Lyon, Auvergne-Rhône-Alpes, 69373, France
Center de Lutte Contre le Cancer (CLCC)
Caen, Calvados, 14076, France
Centre Georges-François Lecler
Dijon, Côte-d'Or, 21079, France
Centre de Lutte Contre le Cancer (CLCC) - Institut de Cancer
Saint-Herblain, Loire-Atlantique, 44805, France
Centre Jean Perrin
Clermont-Ferrand, Puy-de-Dôme, 63011, France
Institut Curie
Paris, Île-de-France Region, 75005, France
Institut Curie - Hôpital René Huguenin
Saint-Cloud, Île-de-France Region, 92210, France
Universitaetsklinikum Tuebingen
Tübingen, Baden-Wurttemberg, 72076, Germany
Universitätsklinikum Erlangen
Erlangen, Bavaria, 91054, Germany
Praxis für Frauenheilkunde Anita
München, Bavaria, 81925, Germany
Marien Hospital Düsseldorf
Düsseldorf, Nordhein-Westfalen, 40479, Germany
Universitaetsklinikum Essen - Klinik fuer Frauenheilkunde
Essen, North Rhine-Westphalia, 45122, Germany
Marien Hospital
Witten, North Rhine-Westphalia, 58452, Germany
Medizinische Fakultät Carl Gustav Carus
Dresden, Saxony, 01307, Germany
Universtatsklinikum Heidelberg Nationales
Heidelberg, Germany
Meir Medical Center
Kfar Saba, Central District, 44281, Israel
Rabin Medical Center - Beilinson Hospital
Petah Tikva, Central District, 49100, Israel
The Chaim Sheba Medical Center - Insititute of Oncology
Ramat Gan, Central District, 52621, Israel
Kaplan Medical Center
Rehovot, Central District, 761001, Israel
Hadassah Medical Organisation, Hadassah Medical Center, Ein-Karem
Jerusalem, Jerusalem, 91120, Israel
Soroka Medical Center [Oncology]
Beersheba, Southern District, 84802, Israel
Clalit Health Services - Lin Medical Center
Haifa, 35152, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, 64239, Israel
PO Garibaldi-Nesima, ARNAS Garibaldi
Catania, Cantania, 95122, Italy
Irccs Irst
Meldola, Forli, 47014, Italy
Istituto di Candiolo, IRCCS
Candiolo, Torino, 10060, Italy
Azienda Ospedaliero Universitaria Senese Universita degli St
Siena, Tuscany, 53100, Italy
Ospedale Umberto I, AOU Ospedali Riuniti Umberto I - GM.Lanc
Ancona, 60126, Italy
AO G.Rummo
Benevento, 82100, Italy
ASST Papa Giovanni XXIII - Oncologia-Bergamo
Bergamo, 24127, Italy
PO di Cremona, ASST di Cremona - Patologia Mammaria e Breast Unit - Cremona
Cremona, 26100, Italy
Arcispedale S.Anna, AOU di Ferrara
Ferrara, 44124, Italy
E.O. Ospedali Galliera
Genova, 16128, Italy
PO A.Manzoni di Lecco, ASST Lecco - Oncologia Medica - Lecco
Lecco, 23900, Italy
Azienda Ospedaliera Fatebenefratelli e Oftalmico
Milan, 20121, Italy
Istituto Europeo di Oncologia Via Ripamonti
Milan, 20141, Italy
AOU Policlinico di Modena
Modena, 41122, Italy
Fondazione Pascale, IRCCS Istituto Nazionale dei Tumori
Napoli, 80131, Italy
AOU di Parma
Parma, 43126, Italy
IRCCS Policlinico San Matteo
Pavia, 27100, Italy
IRCSS Fodazione Salvatore Maugeri
Pavia, 27100, Italy
SO S.Chiara, AOU Pisana
Pisa, 56126, Italy
Nuovo ospedale di Prato
Prato, 59100, Italy
PU Campus Bio-medico di Roma
Roma, 00128, Italy
AO S.Andrea, Università degli Studi di Roma La Sapienza
Roma, 00189, Italy
Ospedale Belcolle Viterbo
Viterbo, 01100, Italy
Maastricht University Medical Centre
Maastricht, Limburg, 6229 HX, Netherlands
Haga Ziekenhuis, loc. Leyenburg
The Hague, South Holland, 2545 CH, Netherlands
MAGODENT Sp. z o.o.
Warsaw, Masovian Voivodeship, 04-125, Poland
Mazowiecki Szpital Onkologiczny
Wieliszew, Masovian Voivodeship, 05-135, Poland
Centrum Onkologii Ziemi Lubelskiej im. Sw. Jana z Dukli
Lublin, 20-090, Poland
Centro Clínico Champalimaud/Fundação Champalimaud
Lisbon, Lisbon District, 1400-038, Portugal
H. Santa Maria - Centro Hospitalar Lisboa Norte
Lisbon, 1649-035, Portugal
Instituto Português Oncologia Francisco Gentil do Porto
Porto, 4200-072, Portugal
Fundacion de Investigacion de Diego
San Juan, 927, Puerto Rico
Seoul National University Hospital
Seoul, Seoul Teugbyeolsi, 03080, South Korea
Severance Hospital, Yonsei University Health System
Seoul, Seoul Teugbyeolsi, 03722, South Korea
Asan Medical Center
Seoul, Seoul Teugbyeolsi, 05505, South Korea
Samsung Medical Center
Seoul, Seoul Teugbyeolsi, 06351, South Korea
H.U.V. del Rocío
Seville, Andalusia, 41013, Spain
Institut Català d'Oncologia-Hospital Germans Trias i Pujol
Badalona, Barcelona, 08916, Spain
Hospital Universitari Parc Taulí
Sabadell, Barcelona, 08208, Spain
Hospital del Mar
Barcelona, Catalonia, 08003, Spain
H.C.U. Valencia
Valencia, Comunidad, 46010, Spain
Hospital de Navarra
Pamplona, Navarre, 31008, Spain
H.U. Sant Joan de Reus
Reus, Tarragona, 43204, Spain
Hospital Ntra. Sra. de Sonsoles
Ávila, 5004, Spain
Hospital Universitario Vall d'Hebron
Barcelona, 08023, Spain
H. San Pedro de Alcántara
Cáceres, 10003, Spain
H.U. Arnau de Vilanova
Lleida, 25198, Spain
M.D. Anderson Cancer Center Madrid
Madrid, 28033, Spain
Hospital Universitario Ramón y Cajal
Madrid, 28034, Spain
Hospital Universitario Clínico San Carlos
Madrid, 28040, Spain
Fundación Instituto Valenciano de Oncología
Valencia, 46009, Spain
Hospital Universitari I Politecnic La Fe
Valencia, 46026, Spain
Guys and St Thomas Hospital
London, City of London, SE1 9RT, United Kingdom
Castle Hill Hospital (Hull)
Hull, East Riding Of Yorkshire, HU16 5JQ, United Kingdom
Kent Oncology Centre, Maidstone Hospital
Maidstone, Kent, ME16 9QQ, United Kingdom
Royal Preston Hospital
Fulwood, Lancashire, PR2 9HT, United Kingdom
South Tees Hospitals NHS Foundation Trust
Middlesbrough, TS4 3BW, United Kingdom
Related Publications (2)
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.
PMID: 36332179DERIVEDRugo 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.
PMID: 33480963DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- VP, Scientific Communications
- Organization
- TerSera Therapeutics LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 6, 2015
First Posted
July 9, 2015
Study Start
August 24, 2015
Primary Completion
August 11, 2021
Study Completion
June 14, 2022
Last Updated
March 17, 2025
Results First Posted
November 23, 2022
Record last verified: 2025-02
Data Sharing
- IPD Sharing
- Will not share