A Single Arm, Open-Label, Phase 2 Study of MGAH22 (Fc-optimized Chimeric Anti-HER2 Monoclonal Antibody) in Patients With Relapsed or Refractory Advanced Breast Cancer Whose Tumors Express HER2 at the 2+ Level by Immunohistochemistry and Lack Evidence of HER2 Gene Amplification by FISH
In the pivotal study that established that Herceptin® was highly effective when added to
standard chemotherapy in the front-line treatment of women with HER2 positive metastatic
breast cancer, benefit appeared to accrue to those patients whose tumors expressed the HER2
oncoprotein at the 3+ level by immunohistochemistry (IHC) or those patients whose tumors
demonstrated evidence of HER2 gene amplification by fluorescence in situ hybridization
(FISH) testing. Similarly, when Herceptin® was used as a single therapy in women with
metastatic breast cancer that had progressed following cytotoxic chemotherapy, 3+
overexpression of HER2, but not 2+ expression, was associated with response to treatment.
These and other studies have led to the recommendation that Herceptin® should be
administered to patients with breast cancer whose tumors exhibit 3+ overexpression or gene
amplification. This study will evaluate whether treatment of patients with tumors that would
not be expected to respond to Herceptin® therapy, namely those that lack HER2 gene
amplification and express the oncoprotein at the 2+ level by IHC, may benefit from the use
of the anti-HER2 monoclonal antibody, MGAH22. If 5 or more responses are seen in 41
evaluable patients, then further clinical development of MGAH22 will be justified.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Response based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria based on Cycle 2, Day 22 computed tomography (CT) scans. This study will employ a Simon two-stage optimum design in which an initial cohort of 21 patients will be treated with MGAH22. If two or more responses (partial or complete response) are seen at the first tumor re-evaluation on day 22 of Cycle 2, the study will be expanded to include up to 41 patients (20 additional patients in Cohort 2, the second stage of the study) in order to determine whether further development of the drug is warranted (5 or more responses in 41 evaluable patients).
Cycle 2, Day 22
Mark D. Pegram, M.D.
United States: Food and Drug Administration
|Stanford University||Stanford, California 94305|
|University of California San Francisco||San Francisco, California 941104206|
|Indiana University||Indianapolis, Indiana 46202|
|Tennessee Oncology||Nashville, Tennessee 37203|
|Florida Cancer Research Institute||Davie, Florida|
|Tufts Cancer Center||Boston, Massachusetts 02111|