Celldex Therapeutics, Inc. (Nasdaq:CLDX) announced that data from the Phase 2 EMERGE study of glembatumumab vedotin in metastatic breast cancer have been published in the Journal of Clinical Oncology. The data from this study supported the initiation of the ongoing, pivotal Phase 2 METRIC study in patients with triple negative breast cancers that over-express glycoprotein NMB (gpNMB). Glembatumumab vedotin is an antibody-drug conjugate that targets and binds to gpNMB, a protein expressed by multiple tumor types, including breast cancer. Overexpression of gpNMB has been shown to promote the invasion and metastasis of cancer and has been associated with poor clinical outcome.
"Previous studies of glembatumumab vedotin suggested that gpNMB over-expression might correlate with the potential anti-cancer activity of glembatumumab vedotin in breast cancer," said Thomas Davis, MD, Executive Vice President and Chief Medical Officer of Celldex Therapeutics. "We designed the EMERGE study to thoroughly explore this hypothesis and observed impressive response rates and prolonged survival in patients that over-expressed gpNMB on the surface of their tumor cells. These data supported the initiation of the METRIC study in patients with triple negative breast cancer—where gpNMB over-expression is seen in approximately 40% of patients. We believe gpNMB could be an important marker in breast cancer and that glembatumumab vedotin holds significant potential as a possible targeted therapy for women facing this disease."
EMERGE was a randomized, multi-center, controlled study. 124 patients with advanced, heavily pre-treated (2-7 lines of prior chemotherapy including a taxane, an anthracycline, capecitabine, and, if HER2-positive, trastuzumab and lapatinib) breast cancer were enrolled and randomized (2:1) to receive glembatumumab vedotin or "Investigator's Choice" (IC) single agent, approved chemotherapy. The primary endpoint of the study was overall response rate. Secondary endpoints included duration of response, progression-free survival, overall survival, safety, and pharmacokinetic and pharmacodynamic analyses. gpNMB expression levels were evaluated via central immunohistochemistry on archived tumor tissue.
Glembatumumab was well tolerated in patients with treatment-refractory breast cancer. The most common treatment-related adverse events were nausea, rash, fatigue, neuropathy, alopecia and neutropenia.
Virtually all patients (99%) with breast cancer screened for potential enrollment into the study expressed gpNMB at or greater than 5%, the predefined expression level required for entry into the study.
A stratification and analysis explored whether intensity of gpNMB expression in malignant epithelial (tumor) cell or stromal tissues was associated with greater treatment effect and determined that:
Low or high expression in the stroma did not generally correlate with outcome after glembatumumab vedotin, although there was a trend towards increased PFS and OS for patients with high stromal intensity.
Patients whose tumors expressed higher levels of gpNMB in malignant epithelial cells ( > 10 and > 25%), had a significantly greater likelihood of tumor response when compared with all other pooled patients. No such correlation was seen in patients treated with IC. Specifically, an ORR of 30% (7/23) was observed for patients with > 25% expression in malignant epithelial cells as compared to 9% (1/11) on the IC arm. This was also associated with improved progression-free survival and overall survival. (PFS: 2.8 ms glembatumumab vs 1.5 ms IC; hazard ratio: 0.63; p=0.18. OS: 10.0 ms glembatumumab vs 5.7 ms IC; hazard ratio 0.67; p=0.31).
In patients with triple negative breast cancer (TNBC), where gpNMB is correlated with the metastatic phenotype and is more frequently expressed, noteworthy activity was observed for glembatumumab vedotin in patients with higher gpNMB expression levels ( > 25% gpNMB expression in malignant epithelial cells), with an ORR of 40% (4/10) for the glembatumumab vedotin arm and 0% (0/6) for the IC arm. An improvement in PFS and OS was also noted (PFS: 3.5 ms glembatumumab vs 1.5 ms IC; hazard ratio 0.11; p=0.0017. OS: 10.0 ms glembatumumab vs 5.5 ms IC; hazard ratio 0.14; p=0.003). (Original Source)
Shares of Celldex Therapeutics closed today at $26.89, up $0.46 or 1.74%. CLDX has a 1-year high of $32.82 and a 1-year low of $10.76. The stock's 50-day moving average is $27.22 and it's 200-day moving average is $19.80.
On the ratings front, Celldex has been the subject of a number of recent research reports. In a report issued on March 11, Cowen analyst Boris Peaker reiterated a Buy rating on CLDX, with a price target of $33, which implies an upside of 26.1% from current levels. Separately, on February 24, Wedbush's David Nierengarten reiterated a Buy rating on the stock and has a price target of $32.
According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Boris Peaker and David Nierengarten have a total average return of 34.1% and 43.5% respectively. Peaker has a success rate of 63.6% and is ranked #31 out of 3568 analysts, while Nierengarten has a success rate of 64.0% and is ranked #20.
Celldex Therapeutics Inc is a biopharmaceutical company. The Company is engaged in the development, manufacturing and commercialization of immunotherapy technologies for the treatment of cancer and other difficult-to-treat diseases.