Linda T. Vahdat, MD
CDX-011 (glembatumumab vedotin, Celldex), a targeted therapy designed to treat patients with advanced breast cancer, appears to increase progression-free survival (PFS) in triple-negative breast cancer patients who have received multiple prior lines of therapy and express the glycoprotein NMB (GPNMB).
The preliminary results of the EMERGE study were presented in a teleconference on Wednesday. In the randomized, multicenter, controlled phase IIB study, 124 women with advanced breast cancer were randomized in an approximately 2:1 ratio to receive either CDX-011 (n=81) or an “investigator’s choice” (IC) single agent chemotherapy (n=36). The primary endpoint of the study was overall response rate.
While the preliminary results of the study did not yield a significant difference in response between all patients who received either CDX-011 or an IC therapy, more pronounced differences were observed in patients with either triple-negative breast cancer or those expressing GPNMB, a protein expressed in breast cancer and other tumors that is associated with tumor migration, invasion, and metastases.
In the triple-negative patients who received CDX-011 (n=36), the response rate was 21%, compared to 0% in the IC arm of the study (n=9). The disease control rate was 71% in the CDX-011 arm compared to 33% in the IC arm, and tumor shrinkage was seen in 54% of CDX-011 patients, compared to 33% in the IC arm.
Similar results were seen among women with a high expression of GPNMB. While 99% of patients in the study had at least a 5% expression of GPNMB in their tumor or stromal tissue, the authors established a threshold of at least 25% of cells expressing the protein to determine a high level of expression.
In the high expression, metastatic breast cancer, arm that received CDX-011 (n=25), the response rate was 32%, the disease control rate was 64%, and tumor shrinkage was observed in 57% of patients. Among those who received the IC therapy (n=8), the response rate was 13%, the disease control rate was 38%, and tumor shrinkage was observed in 38%.
While the authors did not expect to see any statistically significant data because of the small study population, a statistically significant benefit in PFS was observed in patients who had both triple-negative breast cancer and had a high expression GPNMB (P
=.0032). The PFS was approximately three months among this group.
“In heavily pretreated patients, you typically do not observe any kind of progression-free survival beyond the first therapy,” said Linda T. Vahdat, MD, professor of medicine and director of the Breast Cancer Research Program at Weill Cornell Medical College in New York and lead investigator of the EMERGE study. “These patients had a median of six prior therapies, so to have any kind of progression-free survival is exciting from a research standpoint.”
Vahdat cautioned that the data is early. The final results of the study are expected to be released in the fourth quarter of 2012 and will help determine the design of further clinical studies.
CDX-011 is an antibody drug conjugate that consists of fully-human monoclonal antibody, CR011, which is linked to a drug called monomethyl-auristatin E (MMAE). The drug is administered intravenously and binds to GPNMB, where it is then released into the cells and interferes with cell growth and may lead to cell death in the tumor.
In May 2012, CDX-011 was granted fast track designation for the study from the FDA for the treatment of advanced, refractory, or resistant breast cancer patients who expressed GPNMB. Fast track designation is granted when the FDA decides to expedite the review process of a particular drug that can treat serious diseases or fill an unmet medical need.
The company had planned to present the results at the American Society of Clinical Oncology (ASCO) meeting in June. However, a clerical error in which the study was submitted to the incorrect category resulted in ASCO not considering the study for acceptance.