Metastatic or Locally Advanced HER2-positive Breast Cancer MedDRA version: 23.0 Level: PT Classification code 10065430 Term: HER2 positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: LLT Classification code 10
Conditions
Sponsors
MacroGenics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients = 18 years of age. 2. Have 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 (PR) positive or negative. 3. 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. 4. Have received treatment with at least one, and no more than three, lines of therapy overall in the metastatic setting. 5. Resolution of all chemotherapy or radiation-related toxicities to = Grade 1 (with exception of = Grade 2 alopecia, stable sensory neuropathy, or stable electrolyte disturbances that are managed by supplementation). 6. Have life expectancy = 12 weeks. 7. Have acceptable laboratory parameters. 8. Female patients of childbearing potential must have negative pregnancy test performed within 14 days of randomization and on the day of first study treatment. All subjects must agree to use highly effective contraceptive measures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 450 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 158
Exclusion criteria
Exclusion criteria: 1. Patients with 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-detectable brain metastases. 2. History of uncontrolled seizures within 6 months of randomization. 3. History of prior allogeneic bone marrow, stem-cell, or solid organ transplantation. 4. History of clinically significant cardiovascular disease 5. Clinically-significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation. 6. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the 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.;Secondary Objective: •To evaluate PFS, as assessed by study investigators, of margetuximab plus chemotherapy vs. trastuzumab plus chemotherapy in these patients. •To evaluate by independent review the objective response rate (ORR) of margetuximab plus chemotherapy vs. trastuzumab plus chemotherapy in these patients. ;Primary end point(s): Progression-free survival as determined by independent radiological review. Overall survival defined as the number of days from randomization to the date of death (from any cause). ;Timepoint(s) of evaluation of this end point: For PFS: 24 months from the start of the study. For OS: 36 months from the start of the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall response rate (ORR) as determined by independent radiological review. PFS as determined by study investigators. ;Timepoint(s) of evaluation of this end point: For ORR: 36 months from the start of the study. For PFS: 24 months from the start of the study. | — |
Countries
Austria, Belgium, Canada, Czech Republic, Denmark, Finland, France, Germany, Israel, Italy, Korea, Republic of, Netherlands, Poland, Portugal, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactEileen McNulty - Associate Director
MacroGenics, Inc.
Outcome results
None listed