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

MacroGenics

Status and phase: Completed; Phase 3

Conditions: Metastatic Neoplasm; HER-2 Positive Breast Cancer

Treatments: Drug: Physician's choice of chemotherapy.; Biological: Trastuzumab; Biological: Margetuximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02492711

CP-MGAH22-04

Details and patient eligibility

About

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.

Enrollment: 624 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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624 participants in 3 patient groups

Margetuximab plus chemotherapy

Experimental group

Description:

Margetuximab 15 mg/kg every 21 days

Treatment:

Biological: Margetuximab

Drug: Physician's choice of chemotherapy.

Trastuzumab plus chemotherapy

Active Comparator group

Description:

Trastuzumab 8 mg/kg loading dose, then 6 mg/kg every 21 days

Treatment:

Biological: Trastuzumab

Drug: Physician's choice of chemotherapy.

Margetuximab Infusion Sub-study

Experimental group

Description:

Margetuximab 15 mg/kg every 21 days (with or without chemotherapy), studying a shorter duration of infusion beginning in Cycle 2.

Treatment:

Biological: Margetuximab

Drug: Physician's choice of chemotherapy.