TriangleNCT02492711 · CITED IN SOURCE DOCUMENTS
Margetuximab Plus Chemotherapy vs Trastuzumab Plus Chemotherapy in the Treatment of HER2+ Metastatic Breast Cancer
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2025-03-17
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Progression-free Survival (PFS) as Determined by Independent Radiological Review.
Overall Survival (OS) Defined as the Number of Days From Randomization to the Date of Death (From Any Cause).
Number of Patients With Grade 3 or Higher Infusion Related Reactions
To Evaluate Progression-free Survival (PFS), as Assessed by Study Investigators.
To Evaluate the Objective Response Rate (ORR) as Determined by Independent Radiological Review.
Infusion Rate Sub-study All Safety
Adverse events
Limitations, agreements, and source contact
Who could take part
- 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
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Margetuximab 15 mg/kg every 21 days
- intervention Names
- Biological: Margetuximab
- Drug: Physician's choice of chemotherapy.
- label
- Margetuximab plus chemotherapy
- type
- EXPERIMENTAL
- description
- Trastuzumab 8 mg/kg loading dose, then 6 mg/kg every 21 days
- intervention Names
- Biological: Trastuzumab
- Drug: Physician's choice of chemotherapy.
- label
- Trastuzumab plus chemotherapy
- type
- ACTIVE_COMPARATOR
- description
- Margetuximab 15 mg/kg every 21 days (with or without chemotherapy), studying a shorter duration of infusion beginning in Cycle 2.
- intervention Names
- Biological: Margetuximab
- Drug: Physician's choice of chemotherapy.
- label
- Margetuximab Infusion Sub-study
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Margetuximab Infusion Sub-study
- Margetuximab plus chemotherapy
- description
- 15 mg/kg via IV (intravenous) infusion on day 1 of each 21 day cycle,
- name
- Margetuximab
- other Names
- MGAH22
- Margenza®
- type
- BIOLOGICAL
- arm Group Labels
- Trastuzumab plus chemotherapy
- description
- 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
- name
- Trastuzumab
- other Names
- Herceptin®
- type
- BIOLOGICAL
- arm Group Labels
- Margetuximab Infusion Sub-study
- Margetuximab plus chemotherapy
- Trastuzumab plus chemotherapy
- description
- 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
- name
- Physician's choice of chemotherapy.
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 624
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- PFS is measured from the time of randomization until first documented disease progression or death from any cause, whichever is first.
- measure
- 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.
- description
- Overall survival is the time from randomization until death from any cause
- measure
- 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
- description
- 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
- measure
- Number of Patients With Grade 3 or Higher Infusion Related Reactions
- time Frame
- 22 days
- secondary Outcomes
- measure
- 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.
- description
- Objective response rate includes all patients with either a complete response (CR) or a partial response (PR) to study treatment
- measure
- 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.
- description
- Incidence of all grades of infusion-related reactions
- measure
- Infusion Rate Sub-study All Safety
- time Frame
- Throughout the study, average duration 6 months
Full study description
- 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.
Source references
- 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.
- pmid
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- type
- DERIVED
- 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.
- pmid
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- type
- DERIVED
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Preserved source evidence · Not medical advice