June 5, 2010, 3:00 p.m. EDT · Recommend · Post:
Celldex Therapeutics Presents Positive Results from Phase 1/2 Advanced Breast Cancer Study with CDX-011 at 46th Annual ASCO Meeting
Study Achieves Primary Endpoint
CHICAGO, Jun 05, 2010 (BUSINESS WIRE) -- Celldex Therapeutics, Inc. /quotes/comstock/15*!cldx/quotes/nls/cldx (CLDX 6.56, -0.31, -4.51%) today announced that mature results from a Phase 1/2 study evaluating CDX-011 in advanced stage breast cancer patients were presented at the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO). CDX-011 is an experimental antibody-drug conjugate (ADC) directed against glycoprotein NMB (GPNMB) and linked to a potent cancer cell-killing drug, monomethyl-auristatin E (MMAE).
Mature data from this study of CDX-011 show a progression free survival (PFS) rate at 12 weeks of 35% of patients, which is a positive outcome for a heavily treated advanced breast cancer population with very limited treatment options. "The results in triple negative disease are especially encouraging," said Anthony Marucci, President and Chief Executive Officer of Celldex Therapeutics. "A subset analysis using a newly optimized diagnostic assay for GPNMB showed that patients with strong stromal or tumor cell expression of GPNMB may be most likely to respond to CDX-011."
"A reliable and marketable assay to detect a target antigen is critical in the development of any targeted therapy," said Tom Davis, M.D., Chief Medical Officer of Celldex Therapeutics. "We are confident that we can use our GPNMB assay to identify target expression patterns and levels in breast cancer to allow appropriate patient selection in our next study. A Phase 2b trial in advanced, refractory breast cancer is planned, which will select patients on the basis of significant GPNMB expression."
The trial, planned for initiation in Q3-2010, is a Phase 2, randomized, multi-center, controlled trial that will enroll 120 patients with heavily pre-treated, advanced breast cancer who are refractory/resistant to all approved therapies and whose tumors are confirmed to express significant levels of GPNMB via a validated, centralized diagnostic assay. It is anticipated that a significant portion of the enrolled patients will be triple-negative, since GPNMB is frequently expressed in this population. Patients will be randomized (2:1) to receive either CDX-011 or single-agent "Investigator's Choice" chemotherapy. Activity endpoints will include response rate and PFS. The study will be conducted in approximately 25 academic and community sites across the U.S.
Phase 1/2 Breast Cancer Study Overall Results
In the poster entitled Correlation of GPNMB Expression with Outcome in Breast Cancer (BC) Patients Treated with the Antibody-Drug Conjugate (ADC), CDX-011 (CR011-vcMMAE), Celldex described positive results from the Phase 1/2 trial. In this multicenter, open label, Phase 1/2 study, 42 patients with heavily pre-treated (median of seven prior anticancer regimens), progressive, locally advanced or metastatic breast cancer were administered CDX-011 as a 90 minute IV infusion, once every three weeks until intolerance or progression. In the Phase 1 portion of the study, sequential cohorts of patients were treated with escalating doses of CDX-011 to the pre-defined maximum of 1.88 mg/kg once every three weeks. The Phase 2 portion of the study enrolled an expanded cohort of patients at that maximum dose. Enrolled patients were not selected for GPNMB expression. The primary endpoint for the study, PFS rate at 12 weeks for the Phase 2 study portion, has been met, with a 12-week PFS rate of 35% (9 of 26). For all patients treated at the maximum dose level, tumor shrinkage was seen in 62% (16/26) and PFS was 9.1 weeks. A subset of 10 patients had "triple negative disease," a more aggressive breast cancer subtype that carries a high risk of relapse and reduced survival as well as limited therapeutic options due to lack of over-expression of HER2/neu, estrogen and progesterone receptors. In these patients, 78% (7/9) had any tumor shrinkage, 12-week PFS rate was 70% (7/10), and median PFS was 17.9 weeks. Tumor samples from a subset of patients across all dose groups were analyzed for GPNMB expression using a newly developed, validated, centralized assay intended for use in Phase 2 studies of CDX-011 and outcomes were examined for patients with significant stromal and tumor cell expression of GPNMB. In the small subset of patients with significant stromal or tumor cell expression of GPNMB, overall response rate was 22%, median PFS was 17.3 weeks, and the 12-week PFS rate was 67%. The most common treatment-related toxicities were fatigue, rash, nausea, alopecia (hair loss), neutropenia and vomiting.
CDX-011 is an antibody-drug conjugate (ADC) 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. Following intravenous administration, CDX-011 targets and binds to GPNMB, a specific protein that is expressed in more than 40% of breast cancers as well as other tumor types, and which promotes the migration, invasion, and metastasis of breast cancer. Upon internalization into the targeted cell, CDX-011 is designed to release MMAE from CR011 to produce a cell-killing effect. CDX-011 has been shown to be safe and active, with observed objective responses, in two positive trials including the current breast cancer trial and a Phase 1/2 trial in advanced melanoma.
About Celldex Therapeutics, Inc.
Celldex Therapeutics is the first antibody-based combination immunotherapy company. Celldex has a pipeline of drug candidates in development for the treatment of cancer and other difficult-to-treat diseases based on its antibody focused Precision Targeted Immunotherapy Platform. The PTI Platform is a complementary portfolio of monoclonal antibodies, antibody-targeted vaccines and immunomodulators used in optimal combinations 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 (by Celldex and others) of Rindopepimut (PF-04948568 or CDX-110), CDX-1307, CDX-011, CDX-1135 (formerly TP10), CDX-1401, CDX-1127, Belinostat 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 obtain additional capital on acceptable terms, or at all; our ability to adapt APC Targeting Technology(TM) 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; our development partners' willingness to make announcements with respect to co-developed products; 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 Rindopepimut (PF-04948568 or 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; our ability to protect the Company's intellectual property; the loss of any executive officers or key personnel or consultants; our ability to successfully integrate the businesses, multiple technologies and programs of CuraGen and Celldex; 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, 2009, and its Forms 10-Q and 8-K.
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SOURCE: Celldex Therapeutics, Inc.