Celldex Therapeutics Presents Positive Results from Phase 2 Study of the Antibody-Drug Conjugate (ADC) Product Candidate CDX-011 in Advanced Breast Cancer
-- Data Presented at the San Antonio Breast Cancer Symposium --
NEEDHAM, Mass.--(BUSINESS WIRE)--Dec 13, 2009 - Celldex Therapeutics, Inc. (NASDAQ: CLDX) today announced the results of a positive Phase 2 study of CDX-011 (formerly CR011-vcMMAE), in patients with heavily pre-treated, locally advanced or metastatic breast cancers. As presented today at the 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium, the primary efficacy endpoint for the study has been met with significant antitumor activity in patients whose tumors express the target GPNMB. In addition, encouraging results were seen in patients with “triple-negative disease” where treatment options are relatively limited due to lack of hormone receptor or HER2-neu expression.
CDX-011 is the first candidate from the Company's antibody-drug conjugate (ADC) platform, which utilizes fully human monoclonal antibodies to deliver the potent cellular toxin, MMAE, directly to tumor cells by targeting GPNMB. GPNMB is a glycoprotein frequently expressed in a number of tumor types and associated with cancer progression and recurrence. CDX-011 uses the Seattle Genetics MMAE ADC technology, which has established a very promising antitumor effect in advanced clinical studies.
“As seen in this study, treatment with CDX-011 can induce disease regression and stabilization,” said Thomas Davis, M.D., Senior Vice President and Chief Medical Officer of Celldex Therapeutics. “We are very encouraged to see such positive results in patients with triple negative disease – or those with advanced, refractory and heavily pre-treated breast cancers -- where there is a clear unmet medical need. Moving forward, we are planning expanded Phase 2 development focused on patients with tumors expressing GPNMB.”
The Phase 2 study investigated the safety, tolerability and efficacy of CDX-011 in locally advanced or metastatic breast cancer patients who were heavily pre-treated (median of seven prior regimens). The study confirmed the safety of CDX-011 at the pre-defined maximum dose level (1.88 mg/kg) in 6 patients. An additional 28 patients were enrolled as an expanded Phase 2 cohort (for a total of 34 treated patients at 1.88 mg/kg, the Phase 2 dose) to evaluate the progression-free survival (PFS) rate at 12 weeks. As previously seen in melanoma patients, the 1.88 mg/kg dose was well tolerated in this patient population. The primary activity endpoint, which called for at least 5 of 25 (20%) patients in the Phase 2 study portion to be progression-free at twelve weeks, has been met. To date, 9 of 26 (35%) evaluable patients are without progression of disease at twelve weeks.
In addition, at the Phase 2 dose level, 4 of 32 (13%) evaluable patients achieved confirmed or unconfirmed Partial Responses (PR) while 15 of 25 (60%) evaluable patients with measurable disease experienced some reduction in tumor size. GPNMB expression was identified in 10 of 14 (71%) of analyzed tumor samples and treatment with CDX-011 was associated with improved outcomes in all activity parameters in patients whose tumors expressed GPNMB. Notably, in patients who received the Phase 2 dose and whose tumors expressed GPNMB, 2 of 7 (29%) had confirmed Partial Responses, 5 of 7 (71%) had decreases in tumor size, and all 7 achieved at least stable disease with duration from 17.3 to 26.9 weeks. The median PFS in all patients was 9.1 weeks, but in patients whose tumors expressed GPNMB, median PFS was 18.3 weeks, compared to median PFS of 5.9 weeks for patients whose tumors did not express GPNMB. In patients with triple negative disease, 5 of 7 (71%) analyzed samples expressed GPNMB, 7 of 9 (78%) evaluable patients had tumor shrinkage, and the median PFS for these patients was 17.9 weeks.
CDX-011 (formerly CR011-vcMMAE) is an antibody-drug conjugate (ADC) being developed by Celldex Therapeutics, Inc. that consists of a fully-human monoclonal antibody, CR011, linked to a potent cell-killing drug, monomethyl-auristatin E (MMAE). The ADC technology, comprised of MMAE and a stable linker system for attaching it to CR011, was licensed from Seattle Genetics, Inc. The ADC is designed to be stable in the bloodstream. Following intravenous administration, CDX-011 targets and binds to GPNMB, a specific protein that is predominantly expressed in cancerous tumors, including melanoma, breast cancer and gliomas. Upon internalization into the targeted cell, CDX-011 is designed to release MMAE from CR011 to produce a cell-killing effect. CDX-011 is currently completing two Phase 2 trials assessing the safety and efficacy in the treatment of melanoma and for the treatment of metastatic breast cancer, and in a Phase 1 trial to evaluate the safety and activity of alternate dosing schedules.
About Breast Cancer
Breast cancer is the most common cancer in women and a leading cause of death in the United States. According to the American Cancer Society, more than 180,000 women will be diagnosed with invasive breast cancer in 2009 with more than 40,000 deaths attributed to this disease.
Despite recent advances in therapy, the median survival of patients with metastatic breast cancer is 2 to 3 years, while patients with “triple-negative” or “basal-like” breast cancer have limited treatment options and poorer outcomes. Therefore, a significant unmet need remains for novel therapeutic approaches for patients with locally advanced and metastatic breast cancer who have failed other therapies.
About Celldex Therapeutics, Inc.
Celldex Therapeutics is an integrated biopharmaceutical company that applies its comprehensive Precision Targeted Immunotherapy Platform to generate a pipeline of candidates to treat cancer and other difficult-to-treat diseases. Celldex's immunotherapy platform includes a complementary portfolio of monoclonal antibodies, antibody-targeted vaccines and immunomodulators to create novel disease-specific drug candidates. For more information, please visit http://www.celldextherapeutics.com.
Safe Harbor Statement Under the Private Securities Litigation Reform Act of 1995: This release contains “forward-looking statements” made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including those related to the Company's strategic focus and the future development and commercialization of CDX-011 and other products. Forward-looking statements reflect management's current knowledge, assumptions, judgment and expectations regarding future performance or events. Although management believes that the expectations reflected in such statements are reasonable, they give no assurance that such expectations will prove to be correct and you should be aware that actual results could differ materially from those contained in the forward-looking statements. Forward-looking statements are subject to a number of risks and uncertainties, including, but not limited to, our ability to successfully integrate the businesses, multiple technologies and programs of CuraGen and Celldex; our ability to adapt APC Targeting TechnologyTM to develop new, safe and effective vaccines against oncology and infectious disease indications; our ability to successfully complete product research and further development of our programs; the uncertainties inherent in clinical testing; our ability to manage research and development efforts for multiple products at varying stages of development; Pfizer's and our strategy and business plans concerning the continued development and commercialization of CDX-110; the timing, cost and uncertainty of obtaining regulatory approvals; the failure of the market for the Company's programs to continue to develop; the inability to obtain additional capital; the inability to protect the Company's intellectual property; the loss of any executive officers or key personnel or consultants; competition; changes in the regulatory landscape or the imposition of regulations that affect the Company's products; and other risks detailed from time to time in the Company's filings with the Securities and Exchange Commission, including the Company's Form 10-K for the fiscal year ended December 31, 2008, and its Forms 10-Q and 8-K.
Contact: Celldex Therapeutics, Inc.
Anthony S. Marucci, 781-433-0771
President and CEO
Celldex Therapeutics, Inc.
Avery W. Catlin, 781-433-0771
Chief Financial Officer
BMC Communications Group
Matthew Driscoll, 212-477-9007 x20
Posted: December 2009