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.