Clinical trial NCT02492711: Margetuximab Plus Chemotherapy vs Trastuzumab Plus Chemotherapy in the Treatment of HER2+ Metastatic Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HER-2 Positive Breast Cancer
Metastatic Neoplasm
Lead sponsor: MacroGenics
Sponsor class: INDUSTRY
First posted: 2015-07-09
Enrollment: 624
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Progression-free Survival (PFS) as Determined by Independent Radiological Review.
timeFrame: Tumor assessments are conducted every 6 weeks for the first 24 weeks and then every 24 weeks until progression of cancer, average 5 months.
measure: Overall Survival (OS) Defined as the Number of Days From Randomization to the Date of Death (From Any Cause).
timeFrame: Throughout the study, average 21 months
measure: Number of Patients With Grade 3 or Higher Infusion Related Reactions
timeFrame: 22 days
Secondary outcomes:
measure: To Evaluate Progression-free Survival (PFS), as Assessed by Study Investigators.
timeFrame: 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.
measure: To Evaluate the Objective Response Rate (ORR) as Determined by Independent Radiological Review.
timeFrame: 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.
measure: Infusion Rate Sub-study All Safety
timeFrame: Throughout the study, average duration 6 months
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Ironwood Cancer & Research Center
state: Arizona
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Goodyear
country: United States
facility: Western Regional Medical Center, Inc.
state: Arizona
city: Burbank
country: United States
facility: East Valley Hematology And Oncology
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology Oncology Santa Monica
state: California
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco Helen Diller Family Comprehensive Cancer Center
state: California
city: Vallejo
country: United States
facility: Kaiser Permenente Medical Center
state: California
city: Fort Collins
country: United States
facility: Poudre Valley Health Care, Inc.
state: Colorado
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Hollywood
country: United States
facility: Memorial Cancer Institute at Memorial Regional Hospital
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Comprehensive Cancer Center
state: Florida
city: New Port Richey
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Orlando
country: United States
facility: Orlndo Health Cancer Center
state: Florida
city: Port Saint Lucie
country: United States
facility: Hem-Onc Associates
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Piedmont Cancer Institute, P.C.
state: Georgia
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers, PC
state: Georgia
city: Newnan
country: United States
facility: CTCA - Southeastern Regional Medical Center
state: Georgia
city: Honolulu
country: United States
facility: Kaiser Permanente Hawaii Moanalua Medical Center
state: Hawaii
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Zion
country: United States
facility: CTCA - Midwestern Regional Medical Center
state: Illinois
city: Goshen
country: United States
facility: Indiana University Health Goshen Center for Cancer Care
state: Indiana
city: Hazard
country: United States
facility: ARH Cancer Clinic
state: Kentucky
city: Lexington
country: United States
facility: St. Joseph's Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Touro Infirmary Hospital
state: Louisiana
city: Scarborough
country: United States
facility: New England Cancer Specialists
state: Maine
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Boston
country: United States
facility: Tufts-NEMC Cancer Center
state: Massachusetts
city: Hattiesburg
country: United States
facility: Forrest General Hospital
state: Mississippi
city: Kansas City
country: United States
facility: Saint Luke's Cancer Specialists
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital Saint Louis
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock - Norris C
state: New Hampshire
city: Brick
country: United States
facility: New Jersey Hematology Oncology Associates
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Livingston
country: United States
facility: Saint Barnabas Medical Center - The Cancer Center
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Cancer Care Alliance (NMCCA)
state: New Mexico
city: Jamaica
country: United States
facility: Queens Hospital Center
state: New York
city: Lake Success
country: United States
facility: ProHEALTH CARE Associates, LLP
state: New York
city: New York
country: United States
facility: New York University Clinical Cancer Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center (WFUBMC)
state: North Carolina
city: Oklahoma City
country: United States
facility: Mercy Physicians Of Oklahoma
state: Oklahoma
city: Harrisburg
country: United States
facility: Pinnacle Health Cancer Institute
state: Pennsylvania
city: Monongahela
country: United States
facility: Monongahela Valley Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: CTCA - Eastern Regional Medical Center, Inc.
state: Pennsylvania
city: Sayre
country: United States
facility: Guthrie Medical Group, PC
state: Pennsylvania
city: Chattanooga
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: The Sarah Cannon Research Institute
state: Tennessee
city: Austin
country: United States
facility: Austin Cancer Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Fort Worth
country: United States
facility: The Center for Cancer and Blood Disorders
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Fort Belvoir
country: United States
facility: Fort Belvoir Community Hospital
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute/ Swedish Health Services
state: Washington
city: Seattle
country: United States
facility: University of Washington/ Seattle Cancer Care Alliance
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest, PS
state: Washington
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
state: Tirol
city: Edegem
country: Belgium
facility: UZ Antwerpen
state: Antwerpen
city: Wilrijk
country: Belgium
facility: GZA Ziekenhuizen - Campus Sint-Augustinus
state: Antwerpen
city: Ottignies
country: Belgium
facility: Clinique Saint-Pierre Ottignies
state: Brabant Wallon
city: Brussels
country: Belgium
facility: UZ Brussel - Campus Jette
state: Brussels Capital Region
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint-Luc
state: Brussels Capital Region
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis - Campus Virga Jesse
state: Limburg
city: Sint-Niklaas
country: Belgium
facility: AZ Nikolaas - Campus Sint-Niklaas Moerland
state: Oost-Vlaanderen
city: Brugge
country: Belgium
facility: AZ Sint-Jan Brugge - Oostende - Campus Sint-Jan
state: West-Vlaanderen
city: Kortrijk
country: Belgium
facility: AZ Groeninge - Campus Loofstraat
state: West-Vlaanderen
city: Oostende
country: Belgium
facility: AZ Damiaan
state: West-Vlaanderen
city: Liège
country: Belgium
facility: Chc - Clinique Saint-Joseph
city: Namur
country: Belgium
facility: Clinique Sainte Elisabeth
city: Moncton
country: Canada
facility: Dr. Leon Richard Oncology Centre
state: New Brunswick
city: Oshawa
country: Canada
facility: Lakeridge Health Oshawa
state: Ontario
city: Brno
country: Czechia
facility: Masarykuv onkologicky ustav
state: Brno-město
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Aarhus C
country: Denmark
facility: Aarhus Universitetshospital
state: Central Jutland
city: Herning
country: Denmark
facility: Regionshospitalet Herning (Herning Centralsygehus)
state: Central Jutland
city: Vejle
country: Denmark
facility: Vejle Sygehus
state: South Denmark
city: Aarhus N
country: Denmark
facility: Næstved Sygehus
state: Zeeland
city: Tampere
country: Finland
facility: Tampere University Hospital
state: Etelä-Suomen Lääni
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital (HUCH) - Meilahden Sair
state: Länsi-Suomen Lääni
city: Nice
country: France
facility: Center de Lutte Contre le Cancer (CLCC)
state: Alpes-Martitimes
city: Caen cedex 05
country: France
facility: Center de Lutte Contre le Cancer (CLCC)
state: Calvados
city: Dijon
country: France
facility: Centre Georges-François Lecler
state: Côte-d'Or
city: St Herblain
country: France
facility: Centre de Lutte Contre le Cancer (CLCC) - Institut de Cancer
state: Loire-Atlantique
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
state: Puy-de-Dôme
city: Lyon Cedex 08
country: France
facility: Centre Léon Bérard
state: Rhône-Alpes
city: Paris
country: France
facility: Institut Curie
state: Île-de-France
city: Saint-Cloud
country: France
facility: Institut Curie - Hôpital René Huguenin
state: Île-de-France
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
state: Baden-Württemberg
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
state: Bayern
city: München
country: Germany
facility: Praxis für Frauenheilkunde Anita
state: Bayern
city: Düsseldorf
country: Germany
facility: Marien Hospital Düsseldorf
state: Nordhein-Westfalen
city: Essen
country: Germany
facility: Universitaetsklinikum Essen - Klinik fuer Frauenheilkunde
state: Nordrhein-Westfalen
city: Witten
country: Germany
facility: Marien Hospital
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: Medizinische Fakultät Carl Gustav Carus
state: Sachsen
city: Heidelberg
country: Germany
facility: Universtatsklinikum Heidelberg Nationales
city: Beersheba
country: Israel
facility: Soroka Medical Center [Oncology]
state: HaDarom
city: Kfar Saba
country: Israel
facility: Meir Medical Center
state: HaMerkaz
city: Petaẖ Tiqwa
country: Israel
facility: Rabin Medical Center - Beilinson Hospital
state: HaMerkaz
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center - Insititute of Oncology
state: HaMerkaz
city: Rehovot
country: Israel
facility: Kaplan Medical Center
state: HaMerkaz
city: Jerusalem
country: Israel
facility: Hadassah Medical Organisation, Hadassah Medical Center, Ein-Karem
state: Yerushalayim
city: Haifa
country: Israel
facility: Clalit Health Services - Lin Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Catania
country: Italy
facility: PO Garibaldi-Nesima, ARNAS Garibaldi
state: Cantania
city: Meldola
country: Italy
facility: Irccs Irst
state: Forli
city: Candiolo
country: Italy
facility: Istituto di Candiolo, IRCCS
state: Torino
city: Siena
country: Italy
facility: Azienda Ospedaliero Universitaria Senese Universita degli St
state: Toscana
city: Ancona
country: Italy
facility: Ospedale Umberto I, AOU Ospedali Riuniti Umberto I - GM.Lanc
city: Benevento
country: Italy
facility: AO G.Rummo
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII - Oncologia-Bergamo
city: Cremona
country: Italy
facility: PO di Cremona, ASST di Cremona - Patologia Mammaria e Breast Unit - Cremona
city: Ferrara
country: Italy
facility: Arcispedale S.Anna, AOU di Ferrara
city: Genova
country: Italy
facility: E.O. Ospedali Galliera
city: Lecco
country: Italy
facility: PO A.Manzoni di Lecco, ASST Lecco - Oncologia Medica - Lecco
city: Milano
country: Italy
facility: Azienda Ospedaliera Fatebenefratelli e Oftalmico
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia Via Ripamonti
city: Modena
country: Italy
facility: AOU Policlinico di Modena
city: Napoli
country: Italy
facility: Fondazione Pascale, IRCCS Istituto Nazionale dei Tumori
city: Parma
country: Italy
facility: AOU di Parma
city: Pavia
country: Italy
facility: IRCCS Policlinico San Matteo
city: Pavia
country: Italy
facility: IRCSS Fodazione Salvatore Maugeri
city: Pisa
country: Italy
facility: SO S.Chiara, AOU Pisana
city: Prato
country: Italy
facility: Nuovo ospedale di Prato
city: Roma
country: Italy
facility: PU Campus Bio-medico di Roma
city: Roma
country: Italy
facility: AO S.Andrea, Università degli Studi di Roma La Sapienza
city: Viterbo
country: Italy
facility: Ospedale Belcolle Viterbo
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul Teugbyeolsi
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre
state: Limburg
city: Haag
country: Netherlands
facility: Haga Ziekenhuis, loc. Leyenburg
state: Zuid-Holland
city: Warszawa
country: Poland
facility: MAGODENT Sp. z o.o.
state: Mazowieckie
city: Wieliszew
country: Poland
facility: Mazowiecki Szpital Onkologiczny
state: Mazowieckie
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemi Lubelskiej im. Sw. Jana z Dukli
city: Lisbon
country: Portugal
facility: Centro Clínico Champalimaud/Fundação Champalimaud
state: Lisboa
city: Lisboa
country: Portugal
facility: H. Santa Maria - Centro Hospitalar Lisboa Norte
city: Porto
country: Portugal
facility: Instituto Português Oncologia Francisco Gentil do Porto
city: San Juan
country: Puerto Rico
facility: Fundacion de Investigacion de Diego
city: Sevilla
country: Spain
facility: H.U.V. del Rocío
state: Andalucía
city: Badalona
country: Spain
facility: Institut Català d'Oncologia-Hospital Germans Trias i Pujol
state: Barcelona
city: Sabadell
country: Spain
facility: Hospital Universitari Parc Taulí
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital del Mar
state: Catalunya
city: Valencia
country: Spain
facility: H.C.U. Valencia
state: Comunidad
city: Pamplona
country: Spain
facility: Hospital de Navarra
state: Navarra
city: Reus
country: Spain
facility: H.U. Sant Joan de Reus
state: Tarragona
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Cáceres
country: Spain
facility: H. San Pedro de Alcántara
city: Lleida
country: Spain
facility: H.U. Arnau de Vilanova
city: Madrid
country: Spain
facility: M.D. Anderson Cancer Center Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Clínico San Carlos
city: Valencia
country: Spain
facility: Fundación Instituto Valenciano de Oncología
city: Valencia
country: Spain
facility: Hospital Universitari I Politecnic La Fe
city: Ávila
country: Spain
facility: Hospital Ntra. Sra. de Sonsoles
city: London
country: United Kingdom
facility: Guys and St Thomas Hospital
state: City Of London
city: Hull
country: United Kingdom
facility: Castle Hill Hospital (Hull)
state: East Riding Of Yorkshire
city: Maidstone
country: United Kingdom
facility: Kent Oncology Centre, Maidstone Hospital
state: Kent
city: Fulwood
country: United Kingdom
facility: Royal Preston Hospital
state: Lancashire
city: Middlesbrough
country: United Kingdom
facility: South Tees Hospitals NHS Foundation Trust
Study officials:
References:
citation: 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.
citation: 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.