Study Achieves Primary Endpoint
CHICAGO, IL, USA | June 5, 2010 | Celldex Therapeutics, Inc. (NASDAQ: CLDX – News) 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.
About CDX-011
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.
SOURCE: Celldex Therapeutics, Inc.
Post Views: 38
Study Achieves Primary Endpoint
CHICAGO, IL, USA | June 5, 2010 | Celldex Therapeutics, Inc. (NASDAQ: CLDX – News) 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.
About CDX-011
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.
SOURCE: Celldex Therapeutics, Inc.
Post Views: 38
