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

Status: Active

Description

The purpose of this study is to determine whether patients treated with margetuximab plus chemotherapy have longer progression free survival and overall survival than patients treated with trastuzumab plus 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

Locations & Contacts

California

Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: Active
Contact: Kim Kelly
Phone: 310-206-8309
Email: kmkelly@mednet.ucla.edu
Sacramento
University of California Davis Comprehensive Cancer Center
Status: Active
Name Not Available
San Francisco
UCSF Medical Center-Mount Zion
Status: Active
Name Not Available

District of Columbia

Washington
MedStar Georgetown University Hospital
Status: Active
Name Not Available

Illinois

Chicago
Northwestern University
Status: Active
Name Not Available

Maryland

Baltimore
MedStar Franklin Square Medical Center / Weinberg Cancer Institute
Status: Active
Name Not Available
MedStar Union Memorial Hospital
Status: Active
Name Not Available

New Hampshire

Lebanon
Dartmouth Hitchcock Medical Center
Status: Temporarily closed to accrual
Name Not Available

New Mexico

Albuquerque
New Mexico Cancer Care Alliance
Status: Approved
Name Not Available
University of New Mexico Cancer Center
Status: Active
Name Not Available

New York

New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Status: Active
Name Not Available

North Carolina

Winston-Salem
Wake Forest University Health Sciences
Status: Active
Name Not Available

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: Active
Name Not Available

Washington

Seattle
Fred Hutch / University of Washington Cancer Consortium
Status: Active
Name Not Available

Trial Objectives and Outline

An evaluation of 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. A non-randomized sub-study cohort of approximately 78 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.

Trial Phase & Type

Trial Phase

Phase III

Trial Type

Treatment

Lead Organization

Lead Organization
MacroGenics Inc

Trial IDs

Primary ID CP-MGAH22-04
Secondary IDs NCI-2016-00295, s15-00845
Clinicaltrials.gov ID NCT02492711