Margetuximab Plus Chemotherapy vs Trastuzumab Plus Chemotherapy in the Treatment of HER2+ Metastatic Breast Cancer
Condition: HER-2 Positive Breast Cancer; Metastatic Neoplasm
MeSH terms: Breast Neoplasms; Neoplasm Metastasis
Intervention: Margetuximab; Trastuzumab; Physician's choice of chemotherapy.
Intervention description: 15 mg/kg via IV (intravenous) infusion on day 1 of each 21 day cycle,; 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; 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
Intervention MeSH terms: Trastuzumab; Margetuximab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 624.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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