Celldex Therapeutics, Inc. (NASDAQ: CLDX) today announced final results from the Company's randomized Phase 2b EMERGE study of CDX-011 in patients with glycoprotein NMB (GPNMB)-expressing, advanced, heavily pretreated breast cancer. CDX-011 is an antibody-drug conjugate that targets and binds to GPNMB, a specific protein that is expressed in breast cancer which promotes the migration, invasion and metastasis of the disease. It is also highly expressed in triple negative breast cancers where it is associated with increased risk of recurrence. The results presented today at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium confirm preliminary findings reported in May and establish proof of principle with evidence of higher activity in patient subgroups with high GPNMB expression (expression in ≥25% of tumor cells), including those with triple negative disease. Progression free and overall survival benefits were demonstrated in the subgroup of patients with triple negative disease that also highly expressed GPNMB, and strong trends towards benefits were seen in all patients with high GPNMB expression. This benefit in overall survival is seen despite the fact that more than a third of control patients received CDX-011 as a cross over at the time of disease progression.
While the study was not powered to demonstrate statistical significance between the arms, beneficial activity in targeted patient populations that highly expressed GPNMB was consistently observed and, in some cases, was statistically significant. Treatment of patients with both triple negative breast cancer and high GPNMB expression showed high overall response rates (ORR) for the CDX-011 arm (CDX-011 ORR of 33% vs 0% in the Investigator's Choice (IC) arm) and an overall survival and progression free survival (PFS) benefit for CDX-011 that reached statistical significance (CDX-011 median survival of 10.0 months vs IC of 5.5 months; p=0.003); (CDX-011 median PFS of 3.0 months vs IC of 1.5 months; p=0.008). In patients with high GPNMB expression, a high response rate was observed in the CDX-011 arm (CDX-011 ORR of 32% vs IC of 13%) and a trend of improvement in overall survival and PFS was demonstrated for the CDX-011 arm (CDX-011 median survival of 10.0 months vs IC of 5.7 months; p=0.18); (CDX-011 median PFS of 2.7 months vs IC of 1.5 months; p=0.14). For the overall study population, response rates, overall survival and progression free survival after treatment with CDX-011 suggested anti-tumor activity consistent with the standard of care. Patients receiving IC alone who crossed over to receive CDX-011 upon disease progression appeared to represent the better outcomes in the control arm, with a median survival of 12.5 months, as compared to those who did not cross over, with a median of 5.4 months.
"CDX-011 is eliciting impressive response rates in these patients with heavily-pretreated metastatic disease, where physicians typically have little expectation of clinical response. Most importantly, these responses appear to translate into a survival benefit in the patients where we would expect CDX-011 to work best, the targeted patient populations with high levels of GPNMB on the tumor cell surface," said Denise A. Yardley, MD, Senior Investigator in the Breast Cancer Research Program at the Sarah Cannon Research Institute and a lead investigator in the EMERGE study. "Based on these results, it appears that GPNMB is emerging as a potentially important marker in breast cancer and that CDX-011 holds significant potential as a possible targeted therapy for triple negative patients, a patient population that currently has no targeted interventions."
Thomas Davis, MD, Senior Vice President and Chief Medical Officer of Celldex Therapeutics, commented, "The mature results presented today confirm the preliminary results shown previously and support advanced clinical development of CDX-011, which may play a critical role in treating patients with advanced breast cancer. We look forward to discussions with the Food and Drug Administration later this month to design a pivotal study intended to support approval of CDX-011 for specific patients with breast cancer."
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