Phase 2 Trial Update of CDX-011 for Metastatic Breast Cancer

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Celldex Therapeutics announced preliminary results from the Company's randomized Phase 2b EMERGE study of CDX-011 (glembatumumab vedotin) antibody drug conjugate in patients with glycoprotein NMB (GPNMB) expressing, advanced, heavily pretreated breast cancer. GPNMB has been associated with the migration, invasion, and metastasis of breast cancer. It is also highly expressed in triple negative breast cancers where it is associated with increased risk of recurrence.

The Phase 2b EMERGE study required patients' tissue to have at least 5% of cells expressing GPNMB at entry. A total of 122 patients were treated on the study, with 81 patients (81 evaluable) randomized to the CDX-011 arm and 41 patients (36 evaluable) to the IC single-agent chemotherapy arm. Greater than 98% of the patient population across both arms had Stage IV disease. Patients on the CDX-011 arm received a median of six prior courses of therapy and patients on the IC arm received a median of five prior courses of therapy.

Preliminary results suggest that CDX-011 induces impressive response rates compared to current, available therapies in patients with advanced, refractory breast cancers with high GPNMB expression (expression in ≥25% of tumor cells). In this high expressing patient population, treatment with CDX-011 resulted in a 32% overall response rate (ORR; includes confirmed and unconfirmed responses), whereas treatment with Investigator's Choice (IC) single-agent chemotherapy resulted in a 13% ORR. CDX-011 also demonstrated strong response rates in patients with triple negative breast cancer across all levels of GPNMB expression (CDX-011 ORR of 21%; IC ORR of 0%), where treatment options are extremely limited. In addition, in patients with triple negative breast cancer who also highly express GPNMB, greater activity was observed (CDX-011 ORR of 36%; IC ORR of 0%). The ORR across all levels of GPNMB expression was 19% for the CDX-011 arm and 14% for the IC arm, and a direct, positive correlation was observed between increasing levels of GPNMB expression and increased CDX-011 response rates. While data in the study are not yet mature, in patients with high GPNMB in the CDX-011 arm, a trend of improvement in progression-free survival (PFS) has been observed. In patients with both triple negative breast cancer and high GPNMB expression, a statistically significant PFS benefit is currently observed (P=0.0032).

CDX-011 consists of the potent cellular toxin monomethyl-auristatin E (MMAE) conjugated to a fully-human monoclonal antibody (CR011) to transmembrane glycoprotein NMB (GPNMB). The destruction of GPNMB-expressing cells, a novel glycoprotein expressed in over 80% of melanomas, may be involved in growth delay and reduction of a tumor's metastatic potential. CDX-011 is designed to be stable in the bloodstream but to release MMAE upon internalization in GPNMB-expressing tumor cells, resulting in a targeted cell-killing effect.

For more information call (781) 433-0771 or visit www.celldextherapeutics.com.

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