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

HER-2 Positive Breast Cancer Clinical Trial

— SOPHIA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02492711
• Other study ID #: CP-MGAH22-04
• Status: Completed
• Phase: Phase 3
• Start date: August 24, 2015
• Est. completion date: June 14, 2022

Study information

• Verified date: October 2022
• Source: MacroGenics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 624
• Est. completion date: June 14, 2022
• Est. primary completion date: August 11, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• HER-2 Positive Breast Cancer
• Metastatic Neoplasm
• Neoplasm Metastasis

Intervention

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

Drug:
• 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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
MacroGenics

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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
Primary	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	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.
Secondary	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	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.
Secondary	Infusion Rate Sub-study All Safety	Incidence of all grades of infusion-related reactions	Throughout the study, average duration 6 months