We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02492711
Recruitment Status : Completed
First Posted : July 9, 2015
Results First Posted : November 23, 2022
Last Update Posted : November 23, 2022
Sponsor:
Information provided by (Responsible Party):
MacroGenics

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.


Condition or disease Intervention/treatment Phase
HER-2 Positive Breast Cancer Metastatic Neoplasm Biological: Margetuximab Biological: Trastuzumab Drug: Physician's choice of chemotherapy. Phase 3

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 624 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 24, 2015
Actual Primary Completion Date : August 11, 2021
Actual Study Completion Date : June 14, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Margetuximab plus chemotherapy
Margetuximab 15 mg/kg every 21 days
 Biological: Margetuximab
15 mg/kg via IV (intravenous) infusion on day 1 of each 21 day cycle,
Other Names:
  • MGAH22
  • Margenza®

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
Active Comparator: Trastuzumab plus chemotherapy
Trastuzumab 8 mg/kg loading dose, then 6 mg/kg every 21 days
 Biological: 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
Other Name: Herceptin®

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
Experimental: Margetuximab Infusion Sub-study
Margetuximab 15 mg/kg every 21 days (with or without chemotherapy), studying a shorter duration of infusion beginning in Cycle 2.
 Biological: Margetuximab
15 mg/kg via IV (intravenous) infusion on day 1 of each 21 day cycle,
Other Names:
  • MGAH22
  • Margenza®

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


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Progression-free Survival (PFS) as Determined by Independent Radiological Review. [ Time Frame: 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.

  2. Overall Survival (OS) Defined as the Number of Days From Randomization to the Date of Death (From Any Cause). [ Time Frame: Throughout the study, average 21 months ]
    Overall survival is the time from randomization until death from any cause

  3. Number of Patients With Grade 3 or Higher Infusion Related Reactions [ Time Frame: 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 :
  1. To Evaluate Progression-free Survival (PFS), as Assessed by Study Investigators. [ Time Frame: 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. ]
  2. To Evaluate the Objective Response Rate (ORR) as Determined by Independent Radiological Review. [ Time Frame: 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

  3. Infusion Rate Sub-study All Safety [ Time Frame: Throughout the study, average duration 6 months ]
    Incidence of all grades of infusion-related reactions


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02492711


Locations
Show Show 167 study locations
Sponsors and Collaborators
MacroGenics
Investigators
Layout table for investigator information
Study Director: Stephen L Eck, M.D., Ph.D. MacroGenics
  Study Documents (Full-Text)

Documents provided by MacroGenics:
Study Protocol  [PDF] June 8, 2020
Statistical Analysis Plan  [PDF] March 13, 2018

More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT02492711    
Other Study ID Numbers: CP-MGAH22-04
First Posted: July 9, 2015    Key Record Dates
Results First Posted: November 23, 2022
Last Update Posted: November 23, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasm Metastasis
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
 Neoplastic Processes
Pathologic Processes
Trastuzumab
Margetuximab
Antineoplastic Agents, Immunological
Antineoplastic Agents