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

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ClinicalTrials.gov Identifier: NCT02492711
Recruitment Status : Active, not recruiting
First Posted : July 9, 2015
Last Update Posted : December 19, 2020
Sponsor:
Information provided by (Responsible Party):
MacroGenics

Study Description
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Brief Summary:
The purpose of this study is to determine whether patients treated with margetuximab plus chemotherapy have longer progression free survival and overall survival than patients treated with trastuzumab plus chemotherapy.

Condition or disease Intervention/treatment Phase
HER-2 Positive Breast Cancer Metastatic Neoplasm Biological: Margetuximab Biological: Trastuzumab Drug: Capecitabine Drug: Eribulin Drug: Gemcitabine Drug: Vinorelbine Phase 3

Detailed Description:
An evaluation of efficacy, as measured by progression-free survival (PFS) assessed by independent review and overall survival (OS), of margetuximab plus chemotherapy compared with trastuzumab plus chemotherapy in patients with advanced HER2+ breast cancer who 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, and who have received at least one, and no more than three, lines of therapy overall in the metastatic setting. 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.
Study Design
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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
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Trastuzumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Margetuximab plus chemotherapy
Margetuximab 15 mg/kg every 21 days plus Capecitabine 1000 mg/m2 BID for 14 days in a 21-day cycle or Eribulin 1.4 mg/m2 Day 1 and 8 of a 21-day cycle or Gemcitabine 1000 mg/m2 Day 1 and 8 of a 21-day cycle or Vinorelbine 25-30 mg/m2 Day 1 and 8 of a 21-day cycle
 Biological: Margetuximab
15 mg/kg via IV (intravenous) infusion over 120 minutes on day 1 of each 21 day cycle, until progression or unacceptable toxicity develops.

Drug: Capecitabine
1000 mg/m2 BID for 14 days in a 21-day cycle
Other Name: Xeloda®

Drug: Eribulin
1.4 mg/m2 on days 1 and 8 of a 21-day cycle
Other Name: Halaven®

Drug: Gemcitabine
1000 mg/m2 on days 1 and 8 of a 21-day cycle
Other Name: Gemzar ®

Drug: Vinorelbine
25-30 mg/m2 on days 1 and 8 of a 21-day cycle
Other Name: Navelbine®
Active Comparator: Trastuzumab plus chemotherapy
Trastuzumab 8 mg/kg loading dose then 6 mg/kg every 21 days plus Capecitabine 1000 mg/m2 BID for 14 days in a 21-day cycle or Eribulin 1.4 mg/m2 Day 1 and 8 of a 21-day cycle or Gemcitabine 1000 mg/m2 Day 1 and 8 of a 21-day cycle or Vinorelbine 25-30 mg/m2 Day 1 and 8 of a 21-day cycle
 Biological: Trastuzumab
8 mg/kg via IV (intravenous) infusion for the first dose and 6 mg/kg for all subsequent doses via IV infusion over 30-90 minutes on day 1 of each 21 day cycle, until progression or unacceptable toxicity develops.
Other Name: Herceptin®

Drug: Capecitabine
1000 mg/m2 BID for 14 days in a 21-day cycle
Other Name: Xeloda®

Drug: Eribulin
1.4 mg/m2 on days 1 and 8 of a 21-day cycle
Other Name: Halaven®

Drug: Gemcitabine
1000 mg/m2 on days 1 and 8 of a 21-day cycle
Other Name: Gemzar ®

Drug: Vinorelbine
25-30 mg/m2 on days 1 and 8 of a 21-day cycle
Other Name: Navelbine®


Outcome Measures
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Primary Outcome Measures :
  1. Progression-free survival (PFS) as determined by independent radiological review. [ Time Frame: Approximately 41 months after the first subject is randomized; anticipated evaluation Dec 2018 ]
  2. Overall survival (OS) defined as the number of days from randomization to the date of death (from any cause). [ Time Frame: Approximately 15 months after the last subject is randomized; anticipated evaluation Mar 2020 ]
    Overall survival of margetuximab plus chemotherapy compared to trastuzumab plus chemotherapy in patients with advanced HER2+ breast cancer.

  3. Infusion rate sub-study Grade 3 plus safety [ Time Frame: Cycle 2 (21 days) ]
    Incidence of Grade 3 or higher infusion-related reactions


Secondary Outcome Measures :
  1. To evaluate progression-free survival (PFS), as assessed by study investigators. [ Time Frame: PFS will be evaluated approximately 41 months after the first subject is randomized. ]
  2. To evaluate the objective response rate (ORR) as determined by independent radiological review. [ Time Frame: ORR will be evaluated approximately 41 months after the first subject is randomized. ]
  3. Infusion rate sub-study all safety [ Time Frame: Cycle 2 (21 days) ]
    Incidence of all grades of infusion-related reactions


Eligibility Criteria
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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
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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
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Sponsors and Collaborators
MacroGenics
Investigators
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Study Director: Fernanda Arnaldez, M.D. MacroGenics
More Information
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Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT02492711    
Other Study ID Numbers: CP-MGAH22-04
First Posted: July 9, 2015    Key Record Dates
Last Update Posted: December 19, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasm Metastasis
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Gemcitabine
Capecitabine
Trastuzumab
Vinorelbine
Antimetabolites, Antineoplastic
Antimetabolites
 Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators