HER-2 Positive Breast CancerPhase 3SOPHIANCT02492711
Margetuximab Plus Chemotherapy vs Trastuzumab Plus Chemotherapy in the Treatment of HER2+ Metastatic Breast Cancer
A Phase 3 study testing Margetuximab, Trastuzumab and Physician's choice of chemotherapy. in people with HER-2 Positive Breast Cancer and Metastatic Neoplasm, run by MacroGenics at 167 sites in 18 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER-2 Positive Breast Cancer, Metastatic Neoplasm
- What is being tested?
- Margetuximab, Trastuzumab and Physician's choice of chemotherapy.
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 624 participants
- Where
- 167 sitesin 18 countries
- Study dates
- 24 Aug 2015to 14 Jun 2022
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
167 sites in 18 countries.
167 sites in 18 countries
United States62 sites
New Mexico Cancer Care Alliance (NMCCA)
Albuquerque, New Mexico, 87106
Piedmont Cancer Institute, P.C.
Atlanta, Georgia, 30318
Austin Cancer Center
Austin, Texas, 78758
Mercy Medical Center
Baltimore, Maryland, 21202
Tufts-NEMC Cancer Center
Boston, Massachusetts, 02111
New Jersey Hematology Oncology Associates
Brick, New Jersey, 08724
East Valley Hematology And Oncology
Burbank, California, 91505
Ironwood Cancer & Research Center
Chandler, Arizona, 85224
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
Tennessee Oncology, PLLC
Chattanooga, Tennessee, 37404
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
Rush University Medical Center
Chicago, Illinois, 60612
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Inova Schar Cancer Institute
Fairfax, Virginia, 22031
Fort Belvoir Community Hospital
Fort Belvoir, Virginia, 22060
Poudre Valley Health Care, Inc.
Fort Collins, Colorado, 80528
Florida Cancer Specialists
Fort Myers, Florida, 33916
The Center for Cancer and Blood Disorders
Fort Worth, Texas, 76104
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234
Western Regional Medical Center, Inc.
Goodyear, Arizona, 85338
Indiana University Health Goshen Center for Cancer Care
Goshen, Indiana, 46526
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Pinnacle Health Cancer Institute
Harrisburg, Pennsylvania, 17109
Forrest General Hospital
Hattiesburg, Mississippi, 39401
ARH Cancer Clinic
Hazard, Kentucky, 41701
Memorial Cancer Institute at Memorial Regional Hospital
Hollywood, Florida, 33021
Kaiser Permanente Hawaii Moanalua Medical Center
Honolulu, Hawaii, 96819
Queens Hospital Center
Jamaica, New York, 11432
Saint Luke's Cancer Specialists
Kansas City, Missouri, 64111
ProHEALTH CARE Associates, LLP
Lake Success, New York, 11042
Dartmouth-Hitchcock - Norris C
Lebanon, New Hampshire, 03756
St. Joseph's Hospital
Lexington, Kentucky, 40504
Saint Barnabas Medical Center - The Cancer Center
Livingston, New Jersey, 07039
UCLA Hematology Oncology Santa Monica
Los Angeles, California, 90095
Northwest Georgia Oncology Centers, PC
Marietta, Georgia, 30060
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, 33140
Monongahela Valley Hospital
Monongahela, Pennsylvania, 15063
The Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Touro Infirmary Hospital
New Orleans, Louisiana, 70115
Florida Cancer Specialists
New Port Richey, Florida, 34655
New York University Clinical Cancer Center
New York, New York, 10016
CTCA - Southeastern Regional Medical Center
Newnan, Georgia, 30265
Mercy Physicians Of Oklahoma
Oklahoma City, Oklahoma, 73120
Orlndo Health Cancer Center
Orlando, Florida, 32806
CTCA - Eastern Regional Medical Center, Inc.
Philadelphia, Pennsylvania, 19124
Hem-Onc Associates
Port Saint Lucie, Florida, 34952
UC Davis Comprehensive Cancer Center
Sacramento, California, 95817
Utah Cancer Specialists
Salt Lake City, Utah, 84106
Sharp Memorial Hospital
San Diego, California, 92123
University of California, San Francisco Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115
Guthrie Medical Group, PC
Sayre, Pennsylvania, 18840
New England Cancer Specialists
Scarborough, Maine, 04074
Swedish Cancer Institute/ Swedish Health Services
Seattle, Washington, 98104
University of Washington/ Seattle Cancer Care Alliance
Seattle, Washington, 98109
Cancer Care Northwest, PS
Spokane, Washington, 99202
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
Carle Cancer Center
Urbana, Illinois, 61801
Kaiser Permenente Medical Center
Vallejo, California, 94589
MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20010
Palm Beach Cancer Center
West Palm Beach, Florida, 33401
Wake Forest University Baptist Medical Center (WFUBMC)
Winston-Salem, North Carolina, 27157
CTCA - Midwestern Regional Medical Center
Zion, Illinois, 60099
Italy23 sites
Ospedale Umberto I, AOU Ospedali Riuniti Umberto I - GM.Lanc
Ancona, 60126
AO G.Rummo
Benevento, 82100
ASST Papa Giovanni XXIII - Oncologia-Bergamo
Bergamo, 24127
Istituto di Candiolo, IRCCS
Candiolo, Torino, 10060
PO Garibaldi-Nesima, ARNAS Garibaldi
Catania, Cantania, 95122
PO di Cremona, ASST di Cremona - Patologia Mammaria e Breast Unit - Cremona
Cremona, 26100
Arcispedale S.Anna, AOU di Ferrara
Ferrara, 44124
E.O. Ospedali Galliera
Genova, 16128
PO A.Manzoni di Lecco, ASST Lecco - Oncologia Medica - Lecco
Lecco, 23900
Irccs Irst
Meldola, Forli, 47014
Azienda Ospedaliera Fatebenefratelli e Oftalmico
Milan, 20121
Istituto Europeo di Oncologia Via Ripamonti
Milan, 20141
AOU Policlinico di Modena
Modena, 41122
Fondazione Pascale, IRCCS Istituto Nazionale dei Tumori
Naples, 80131
AOU di Parma
Parma, 43126
IRCCS Policlinico San Matteo
Pavia, 27100
IRCSS Fodazione Salvatore Maugeri
Pavia, 27100
SO S.Chiara, AOU Pisana
Pisa, 56126
Nuovo ospedale di Prato
Prato, 59100
PU Campus Bio-medico di Roma
Roma, 00128
AO S.Andrea, Università degli Studi di Roma La Sapienza
Roma, 00189
Azienda Ospedaliero Universitaria Senese Universita degli St
Siena, Tuscany, 53100
Ospedale Belcolle Viterbo
Viterbo, 01100
Spain16 sites
Hospital Ntra. Sra. de Sonsoles
Ávila, 5004
Institut Català d'Oncologia-Hospital Germans Trias i Pujol
Badalona, Barcelona, 08916
Hospital del Mar
Barcelona, Catalonia, 08003
Hospital Universitario Vall d'Hebron
Barcelona, 08023
H. San Pedro de Alcántara
Cáceres, 10003
H.U. Arnau de Vilanova
Lleida, 25198
M.D. Anderson Cancer Center Madrid
Madrid, 28033
Hospital Universitario Ramón y Cajal
Madrid, 28034
Hospital Universitario Clínico San Carlos
Madrid, 28040
Hospital de Navarra
Pamplona, Navarre, 31008
H.U. Sant Joan de Reus
Reus, Tarragona, 43204
Hospital Universitari Parc Taulí
Sabadell, Barcelona, 08208
H.U.V. del Rocío
Seville, Andalusia, 41013
H.C.U. Valencia
Valencia, Comunidad, 46010
Fundación Instituto Valenciano de Oncología
Valencia, 46009
Hospital Universitari I Politecnic La Fe
Valencia, 46026
Belgium12 sites
AZ Sint-Jan Brugge - Oostende - Campus Sint-Jan
Bruges, West-Vlaanderen, 8000
UZ Brussel - Campus Jette
Brussels, Brussels Capital, 1090
Cliniques universitaires Saint-Luc
Brussels, Brussels Capital, 1200
UZ Antwerpen
Edegem, Antwerpen, 2650
Jessa Ziekenhuis - Campus Virga Jesse
Hasselt, Limburg, 3500
AZ Groeninge - Campus Loofstraat
Kortrijk, West-Vlaanderen, 8500
Chc - Clinique Saint-Joseph
Liège, 4000
Clinique Sainte Elisabeth
Namur, 5000
AZ Damiaan
Ostend, West-Vlaanderen, 8400
Clinique Saint-Pierre Ottignies
Ottignies, Brabant Wallon, 1340
AZ Nikolaas - Campus Sint-Niklaas Moerland
Sint-Niklaas, Oost-Vlaanderen, 9100
GZA Ziekenhuizen - Campus Sint-Augustinus
Wilrijk, Antwerpen, 2610
France8 sites
Center de Lutte Contre le Cancer (CLCC)
Caen, Calvados, 14076
Centre Jean Perrin
Clermont-Ferrand, Puy-de-Dôme, 63011
Centre Georges-François Lecler
Dijon, Côte-d'Or, 21079
Centre Léon Bérard
Lyon, Auvergne-Rhône-Alpes, 69373
Center de Lutte Contre le Cancer (CLCC)
Nice, Alpes-Martitimes, 06189
Institut Curie
Paris, Île-de-France Region, 75005
Institut Curie - Hôpital René Huguenin
Saint-Cloud, Île-de-France Region, 92210
Centre de Lutte Contre le Cancer (CLCC) - Institut de Cancer
Saint-Herblain, Loire-Atlantique, 44805
Germany8 sites
Medizinische Fakultät Carl Gustav Carus
Dresden, Saxony, 01307
Marien Hospital Düsseldorf
Düsseldorf, Nordhein-Westfalen, 40479
Universitätsklinikum Erlangen
Erlangen, Bavaria, 91054
Universitaetsklinikum Essen - Klinik fuer Frauenheilkunde
Essen, North Rhine-Westphalia, 45122
Universtatsklinikum Heidelberg Nationales
Heidelberg
Praxis für Frauenheilkunde Anita
München, Bavaria, 81925
Universitaetsklinikum Tuebingen
Tübingen, Baden-Wurttemberg, 72076
Marien Hospital
Witten, North Rhine-Westphalia, 58452
Israel8 sites
Soroka Medical Center [Oncology]
Beersheba, Southern District, 84802
Clalit Health Services - Lin Medical Center
Haifa, 35152
Hadassah Medical Organisation, Hadassah Medical Center, Ein-Karem
Jerusalem, Jerusalem, 91120
Meir Medical Center
Kfar Saba, Central District, 44281
Rabin Medical Center - Beilinson Hospital
Petah Tikva, Central District, 49100
The Chaim Sheba Medical Center - Insititute of Oncology
Ramat Gan, Central District, 52621
Kaplan Medical Center
Rehovot, Central District, 761001
Tel Aviv Sourasky Medical Center
Tel Aviv, 64239
United Kingdom5 sites
Royal Preston Hospital
Fulwood, Lancashire, PR2 9HT
Castle Hill Hospital (Hull)
Hull, East Riding Of Yorkshire, HU16 5JQ
Guys and St Thomas Hospital
London, City of London, SE1 9RT
Kent Oncology Centre, Maidstone Hospital
Maidstone, Kent, ME16 9QQ
South Tees Hospitals NHS Foundation Trust
Middlesbrough, TS4 3BW
Denmark4 sites
Aarhus Universitetshospital
Aarhus C, Central Jutland, 8000
Næstved Sygehus
Aarhus N, Region Sjælland, 4700
Regionshospitalet Herning (Herning Centralsygehus)
Herning, Central Jutland, 7400
Vejle Sygehus
Vejle, Region Syddanmark, 7100
South Korea4 sites
Seoul National University Hospital
Seoul, Seoul Teugbyeolsi, 03080
Severance Hospital, Yonsei University Health System
Seoul, Seoul Teugbyeolsi, 03722
Asan Medical Center
Seoul, Seoul Teugbyeolsi, 05505
Samsung Medical Center
Seoul, Seoul Teugbyeolsi, 06351
Czechia3 sites
Masarykuv onkologicky ustav
Brno, Brno-město, 656 53
Fakultni nemocnice Olomouc
Olomouc, 779 00
Fakultni nemocnice v Motole
Prague, 150 06
Poland3 sites
Centrum Onkologii Ziemi Lubelskiej im. Sw. Jana z Dukli
Lublin, 20-090
MAGODENT Sp. z o.o.
Warsaw, Masovian Voivodeship, 04-125
Mazowiecki Szpital Onkologiczny
Wieliszew, Masovian Voivodeship, 05-135
Portugal3 sites
Centro Clínico Champalimaud/Fundação Champalimaud
Lisbon, Lisbon District, 1400-038
H. Santa Maria - Centro Hospitalar Lisboa Norte
Lisbon, 1649-035
Instituto Português Oncologia Francisco Gentil do Porto
Porto, 4200-072
Canada2 sites
Dr. Leon Richard Oncology Centre
Moncton, New Brunswick, E1C 8X3
Lakeridge Health Oshawa
Oshawa, Ontario, L1G 2B9
Finland2 sites
Helsinki University Central Hospital (HUCH) - Meilahden Sair
Helsinki, Länsi-Suomen Lääni, 00029
Tampere University Hospital
Tampere, Etelä-Suomen Lääni, 33521
Netherlands2 sites
Maastricht University Medical Centre
Maastricht, Limburg, 6229 HX
Haga Ziekenhuis, loc. Leyenburg
The Hague, South Holland, 2545 CH
About this study
Official title: 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
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.
- Conditions
- HER-2 Positive Breast Cancer, Metastatic Neoplasm
- Being tested
- Margetuximab, Trastuzumab, Physician's choice of chemotherapy.
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MargetuximabBiological
Also called MGAH22, Margenza®
15 mg/kg via IV (intravenous) infusion on day 1 of each 21 day cycle,
TrastuzumabBiological
Also called Herceptin®
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.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
| Study group | Role | What they receive |
|---|---|---|
| Margetuximab plus chemotherapy | Experimental | Margetuximab 15 mg/kg every 21 days Receives: Biological: Margetuximab; Drug: Physician's choice of chemotherapy. |
| Trastuzumab plus chemotherapy | Active comparator | Trastuzumab 8 mg/kg loading dose, then 6 mg/kg every 21 days Receives: Biological: Trastuzumab; Drug: Physician's choice of chemotherapy. |
| Margetuximab Infusion Sub-study | Experimental | Margetuximab 15 mg/kg every 21 days (with or without chemotherapy), studying a shorter duration of infusion beginning in Cycle 2. Receives: Biological: Margetuximab; Drug: Physician's choice of chemotherapy. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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
Measured: 22 days
Secondary outcomes (3)
To Evaluate Progression-free Survival (PFS), as Assessed by Study Investigators.
Measured: 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.
Objective response rate includes all patients with either a complete response (CR) or a partial response (PR) to study treatment
Measured: 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
Incidence of all grades of infusion-related reactions
Measured: Throughout the study, average duration 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2015 (estimated)
- Study start24 Aug 2015
- Primary completion11 Aug 2021
- Study completion14 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HER-2 Positive Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 624 participants (actual)
Sponsor and investigators
- Lead sponsor
- MacroGenics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02492711
- Sponsor's protocol ID
- CP-MGAH22-04
- Acronym
- SOPHIA
- Status last verified
- Feb 2025
- First submitted
- 6 Jul 2015
- Last updated
- 17 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 36332179Rugo 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.
PubMed 33480963