Phase 3
Completed N=624
Margetuximab Plus Chemotherapy vs Trastuzumab Plus Chemotherapy in the Treatment of HER2+ Metastatic Breast Cancer
HER-2 Positive Breast Cancer · Metastatic Neoplasm
Source: ClinicalTrials.gov NCT02492711 ↗
Enrolled (actual)
624
Serious AEs
18.6%
Results posted
Nov 2022
Primary outcomePrimary: Progression-free Survival (PFS) as Determined by Independent Radiological Review. — 5.8; 4.9 months — p=0.0334
◆ Published Evidence
Highly cited
348citations · ~70 / year
Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized 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.
Linked Publications (2)
-
Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial.
-
Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression-free Survival (PFS) as Determined by Independent Radiological Review. |
5.8; 4.9 | 0.0334 sig |
| PRIMARY Overall Survival (OS) Defined as the Number of Days From Randomization to the Date of Death (From Any Cause). |
21.6; 21.9 | 0.6204 |
| PRIMARY Number of Patients With Grade 3 or Higher Infusion Related Reactions |
0; 0; 0 | — |
| SECONDARY To Evaluate Progression-free Survival (PFS), as Assessed by Study Investigators. |
5.6; 4.2 | 0.0014 sig |
| SECONDARY To Evaluate the Objective Response Rate (ORR) as Determined by Independent Radiological Review. |
7; 4; 51; 38; 204; 220 | — |
| SECONDARY Infusion Rate Sub-study All Safety |
1; 1; 16; 0; 0; 2 | — |
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
Data sourced from ClinicalTrials.gov (NCT02492711) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.