Margetuximab Plus Chemotherapy vs Trastuzumab Plus Chemotherapy in the Treatment of HER2+ Metastatic Breast Cancer
- Conditions
- HER-2 Positive Breast CancerMetastatic Neoplasm
- Interventions
- Biological: MargetuximabBiological: TrastuzumabDrug: Physician's choice of chemotherapy.
- Registration Number
- NCT02492711
- Lead Sponsor
- MacroGenics
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 624
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Margetuximab plus chemotherapy Margetuximab Margetuximab 15 mg/kg every 21 days Margetuximab plus chemotherapy Physician's choice of chemotherapy. Margetuximab 15 mg/kg every 21 days Trastuzumab plus chemotherapy Trastuzumab Trastuzumab 8 mg/kg loading dose, then 6 mg/kg every 21 days Trastuzumab plus chemotherapy Physician's choice of chemotherapy. Trastuzumab 8 mg/kg loading dose, then 6 mg/kg every 21 days Margetuximab Infusion Sub-study Margetuximab Margetuximab 15 mg/kg every 21 days (with or without chemotherapy), studying a shorter duration of infusion beginning in Cycle 2. Margetuximab Infusion Sub-study Physician's choice of chemotherapy. Margetuximab 15 mg/kg every 21 days (with or without chemotherapy), studying a shorter duration of infusion beginning in Cycle 2.
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) 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, average 5 months. PFS is measured from the time of randomization until first documented disease progression or death from any cause, whichever is first.
Overall Survival (OS) Defined as the Number of Days From Randomization to the Date of Death (From Any Cause). Throughout the study, average 21 months Overall survival is the time from randomization until death from any cause
Number of Patients With Grade 3 or Higher Infusion Related Reactions 22 days 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
- Secondary Outcome Measures
Name Time Method 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. Objective response rate includes all patients with either a complete response (CR) or a partial response (PR) to study treatment
Infusion Rate Sub-study All Safety Throughout the study, average duration 6 months Incidence of all grades of infusion-related reactions
Trial Locations
- Locations (165)
East Valley Hematology And Oncology
🇺🇸Burbank, California, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Tennessee Oncology, PLLC
🇺🇸Chattanooga, Tennessee, United States
UCLA Hematology Oncology Santa Monica
🇺🇸Los Angeles, California, United States
Memorial Cancer Institute at Memorial Regional Hospital
🇺🇸Hollywood, Florida, United States
Saint Barnabas Medical Center - The Cancer Center
🇺🇸Livingston, New Jersey, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Inova Schar Cancer Institute
🇺🇸Fairfax, Virginia, United States
AZ Groeninge - Campus Loofstraat
🇧🇪Kortrijk, West-Vlaanderen, Belgium
Clinique Sainte Elisabeth
🇧🇪Namur, Belgium
Jessa Ziekenhuis - Campus Virga Jesse
🇧🇪Hasselt, Limburg, Belgium
Centre Jean Perrin
🇫🇷Clermont-Ferrand, Puy-de-Dôme, France
Mazowiecki Szpital Onkologiczny
🇵🇱Wieliszew, Mazowieckie, Poland
Tufts-NEMC Cancer Center
🇺🇸Boston, Massachusetts, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Swedish Cancer Institute/ Swedish Health Services
🇺🇸Seattle, Washington, United States
University of Washington/ Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Institut Curie
🇫🇷Paris, Île-de-France, France
Institut Curie - Hôpital René Huguenin
🇫🇷Saint-Cloud, Île-de-France, France
Kent Oncology Centre, Maidstone Hospital
🇬🇧Maidstone, Kent, United Kingdom
Centre Georges-François Lecler
🇫🇷Dijon, Côte-d'Or, France
Sharp Memorial Hospital
🇺🇸San Diego, California, United States
University of California, San Francisco Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
The Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Mercy Physicians Of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
Utah Cancer Specialists
🇺🇸Salt Lake City, Utah, United States
Aarhus Universitetshospital
🇩🇰Aarhus C, Central Jutland, Denmark
Regionshospitalet Herning (Herning Centralsygehus)
🇩🇰Herning, Central Jutland, Denmark
ASST Papa Giovanni XXIII - Oncologia-Bergamo
🇮🇹Bergamo, Italy
Hem-Onc Associates
🇺🇸Port Saint Lucie, Florida, United States
Kaiser Permenente Medical Center
🇺🇸Vallejo, California, United States
Palm Beach Cancer Center
🇺🇸West Palm Beach, Florida, United States
Piedmont Cancer Institute, P.C.
🇺🇸Atlanta, Georgia, United States
Western Regional Medical Center, Inc.
🇺🇸Goodyear, Arizona, United States
Cliniques universitaires Saint-Luc
🇧🇪Brussels, Brussels Capital Region, Belgium
Florida Cancer Specialists
🇺🇸New Port Richey, Florida, United States
CTCA - Southeastern Regional Medical Center
🇺🇸Newnan, Georgia, United States
Queens Hospital Center
🇺🇸Jamaica, New York, United States
PO di Cremona, ASST di Cremona - Patologia Mammaria e Breast Unit - Cremona
🇮🇹Cremona, Italy
AOU di Parma
🇮🇹Parma, Italy
AO S.Andrea, Università degli Studi di Roma La Sapienza
🇮🇹Roma, Italy
H.C.U. Valencia
🇪🇸Valencia, Comunidad, Spain
South Tees Hospitals NHS Foundation Trust
🇬🇧Middlesbrough, United Kingdom
Hospital del Mar
🇪🇸Barcelona, Catalunya, Spain
Samsung Medical Center
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Ironwood Cancer & Research Center
🇺🇸Chandler, Arizona, United States
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Poudre Valley Health Care, Inc.
🇺🇸Fort Collins, Colorado, United States
MedStar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Mount Sinai Comprehensive Cancer Center
🇺🇸Miami Beach, Florida, United States
Northwest Georgia Oncology Centers, PC
🇺🇸Marietta, Georgia, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
CTCA - Midwestern Regional Medical Center
🇺🇸Zion, Illinois, United States
ARH Cancer Clinic
🇺🇸Hazard, Kentucky, United States
New England Cancer Specialists
🇺🇸Scarborough, Maine, United States
Forrest General Hospital
🇺🇸Hattiesburg, Mississippi, United States
Mercy Medical Center
🇺🇸Baltimore, Maryland, United States
Mercy Hospital Saint Louis
🇺🇸Saint Louis, Missouri, United States
Dartmouth-Hitchcock - Norris C
🇺🇸Lebanon, New Hampshire, United States
New Jersey Hematology Oncology Associates
🇺🇸Brick, New Jersey, United States
New Mexico Cancer Care Alliance (NMCCA)
🇺🇸Albuquerque, New Mexico, United States
ProHEALTH CARE Associates, LLP
🇺🇸Lake Success, New York, United States
New York University Clinical Cancer Center
🇺🇸New York, New York, United States
Monongahela Valley Hospital
🇺🇸Monongahela, Pennsylvania, United States
CTCA - Eastern Regional Medical Center, Inc.
🇺🇸Philadelphia, Pennsylvania, United States
University of Virginia Cancer Center
🇺🇸Charlottesville, Virginia, United States
Fort Belvoir Community Hospital
🇺🇸Fort Belvoir, Virginia, United States
UZ Antwerpen
🇧🇪Edegem, Antwerpen, Belgium
Cancer Care Northwest, PS
🇺🇸Spokane, Washington, United States
GZA Ziekenhuizen - Campus Sint-Augustinus
🇧🇪Wilrijk, Antwerpen, Belgium
Clinique Saint-Pierre Ottignies
🇧🇪Ottignies, Brabant Wallon, Belgium
UZ Brussel - Campus Jette
🇧🇪Brussels, Brussels Capital Region, Belgium
AZ Sint-Jan Brugge - Oostende - Campus Sint-Jan
🇧🇪Brugge, West-Vlaanderen, Belgium
Chc - Clinique Saint-Joseph
🇧🇪Liège, Belgium
AZ Damiaan
🇧🇪Oostende, West-Vlaanderen, Belgium
Dr. Leon Richard Oncology Centre
🇨🇦Moncton, New Brunswick, Canada
Fakultni nemocnice Olomouc
🇨🇿Olomouc, Czechia
Masarykuv onkologicky ustav
🇨🇿Brno, Brno-město, Czechia
Lakeridge Health Oshawa
🇨🇦Oshawa, Ontario, Canada
Fakultni nemocnice v Motole
🇨🇿Praha 5, Czechia
Vejle Sygehus
🇩🇰Vejle, South Denmark, Denmark
Tampere University Hospital
🇫🇮Tampere, Etelä-Suomen Lääni, Finland
Næstved Sygehus
🇩🇰Aarhus N, Zeeland, Denmark
Helsinki University Central Hospital (HUCH) - Meilahden Sair
🇫🇮Helsinki, Länsi-Suomen Lääni, Finland
Center de Lutte Contre le Cancer (CLCC)
🇫🇷Caen cedex 05, Calvados, France
Centre Léon Bérard
🇫🇷Lyon Cedex 08, Rhône-Alpes, France
Universitaetsklinikum Tuebingen
🇩🇪Tuebingen, Baden-Württemberg, Germany
Marien Hospital Düsseldorf
🇩🇪Düsseldorf, Nordhein-Westfalen, Germany
Universitätsklinikum Erlangen
🇩🇪Erlangen, Bayern, Germany
Universitaetsklinikum Essen - Klinik fuer Frauenheilkunde
🇩🇪Essen, Nordrhein-Westfalen, Germany
Rabin Medical Center - Beilinson Hospital
🇮🇱Petaẖ Tiqwa, HaMerkaz, Israel
Medizinische Fakultät Carl Gustav Carus
🇩🇪Dresden, Sachsen, Germany
Universtatsklinikum Heidelberg Nationales
🇩🇪Heidelberg, Germany
Marien Hospital
🇩🇪Witten, Nordrhein-Westfalen, Germany
Soroka Medical Center [Oncology]
🇮🇱Beersheba, HaDarom, Israel
Meir Medical Center
🇮🇱Kfar Saba, HaMerkaz, Israel
Clalit Health Services - Lin Medical Center
🇮🇱Haifa, Israel
Hadassah Medical Organisation, Hadassah Medical Center, Ein-Karem
🇮🇱Jerusalem, Yerushalayim, Israel
Kaplan Medical Center
🇮🇱Rehovot, HaMerkaz, Israel
The Chaim Sheba Medical Center - Insititute of Oncology
🇮🇱Ramat Gan, HaMerkaz, Israel
Irccs Irst
🇮🇹Meldola, Forli, Italy
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
PO Garibaldi-Nesima, ARNAS Garibaldi
🇮🇹Catania, Cantania, Italy
Azienda Ospedaliero Universitaria Senese Universita degli St
🇮🇹Siena, Toscana, Italy
AO G.Rummo
🇮🇹Benevento, Italy
Istituto di Candiolo, IRCCS
🇮🇹Candiolo, Torino, Italy
Ospedale Umberto I, AOU Ospedali Riuniti Umberto I - GM.Lanc
🇮🇹Ancona, Italy
Arcispedale S.Anna, AOU di Ferrara
🇮🇹Ferrara, Italy
E.O. Ospedali Galliera
🇮🇹Genova, Italy
PO A.Manzoni di Lecco, ASST Lecco - Oncologia Medica - Lecco
🇮🇹Lecco, Italy
Azienda Ospedaliera Fatebenefratelli e Oftalmico
🇮🇹Milano, Italy
Istituto Europeo di Oncologia Via Ripamonti
🇮🇹Milano, Italy
AOU Policlinico di Modena
🇮🇹Modena, Italy
IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
IRCSS Fodazione Salvatore Maugeri
🇮🇹Pavia, Italy
SO S.Chiara, AOU Pisana
🇮🇹Pisa, Italy
PU Campus Bio-medico di Roma
🇮🇹Roma, Italy
Nuovo ospedale di Prato
🇮🇹Prato, Italy
Fondazione Pascale, IRCCS Istituto Nazionale dei Tumori
🇮🇹Napoli, Italy
Ospedale Belcolle Viterbo
🇮🇹Viterbo, Italy
Fundacion de Investigacion de Diego
🇵🇷San Juan, Puerto Rico
Seoul National University Hospital
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Haga Ziekenhuis, loc. Leyenburg
🇳🇱Haag, Zuid-Holland, Netherlands
Centrum Onkologii Ziemi Lubelskiej im. Sw. Jana z Dukli
🇵🇱Lublin, Poland
Instituto Português Oncologia Francisco Gentil do Porto
🇵🇹Porto, Portugal
H. Santa Maria - Centro Hospitalar Lisboa Norte
🇵🇹Lisboa, Portugal
H.U.V. del Rocío
🇪🇸Sevilla, Andalucía, Spain
Institut Català d'Oncologia-Hospital Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Hospital Universitari Parc Taulí
🇪🇸Sabadell, Barcelona, Spain
Hospital de Navarra
🇪🇸Pamplona, Navarra, Spain
H.U. Sant Joan de Reus
🇪🇸Reus, Tarragona, Spain
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
H. San Pedro de Alcántara
🇪🇸Cáceres, Spain
H.U. Arnau de Vilanova
🇪🇸Lleida, Spain
Fundación Instituto Valenciano de Oncología
🇪🇸Valencia, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
M.D. Anderson Cancer Center Madrid
🇪🇸Madrid, Spain
Hospital Universitari I Politecnic La Fe
🇪🇸Valencia, Spain
Hospital Ntra. Sra. de Sonsoles
🇪🇸Ávila, Spain
Guys and St Thomas Hospital
🇬🇧London, City Of London, United Kingdom
Castle Hill Hospital (Hull)
🇬🇧Hull, East Riding Of Yorkshire, United Kingdom
Royal Preston Hospital
🇬🇧Fulwood, Lancashire, United Kingdom
Praxis für Frauenheilkunde Anita
🇩🇪München, Bayern, Germany
Indiana University Health Goshen Center for Cancer Care
🇺🇸Goshen, Indiana, United States
Northwestern University Feinberg School of Medicine
🇺🇸Chicago, Illinois, United States
Pinnacle Health Cancer Institute
🇺🇸Harrisburg, Pennsylvania, United States
The Center for Cancer and Blood Disorders
🇺🇸Fort Worth, Texas, United States
Guthrie Medical Group, PC
🇺🇸Sayre, Pennsylvania, United States
UC Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Orlndo Health Cancer Center
🇺🇸Orlando, Florida, United States
Wake Forest University Baptist Medical Center (WFUBMC)
🇺🇸Winston-Salem, North Carolina, United States
Hospital Universitario Clínico San Carlos
🇪🇸Madrid, Spain
AZ Nikolaas - Campus Sint-Niklaas Moerland
🇧🇪Sint-Niklaas, Oost-Vlaanderen, Belgium
Centre de Lutte Contre le Cancer (CLCC) - Institut de Cancer
🇫🇷St Herblain, Loire-Atlantique, France
MAGODENT Sp. z o.o.
🇵🇱Warszawa, Mazowieckie, Poland
Centro Clínico Champalimaud/Fundação Champalimaud
🇵🇹Lisbon, Lisboa, Portugal
Maastricht University Medical Centre
🇳🇱Maastricht, Limburg, Netherlands
Saint Luke's Cancer Specialists
🇺🇸Kansas City, Missouri, United States
Kaiser Permanente Hawaii Moanalua Medical Center
🇺🇸Honolulu, Hawaii, United States
Austin Cancer Center
🇺🇸Austin, Texas, United States
Touro Infirmary Hospital
🇺🇸New Orleans, Louisiana, United States
St. Joseph's Hospital
🇺🇸Lexington, Kentucky, United States
Medizinische Universität Innsbruck
🇦🇹Innsbruck, Tirol, Austria
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