REDWOOD CITY, CA, USA I February 4, 2015 I OncoMed Pharmaceuticals, Inc. (OMED), a clinical-stage company developing novel therapeutics that target cancer stem cells (CSCs), or tumor-initiating cells, announced that patient dosing has begun in the double-blinded, placebo-controlled, randomized Phase 2 clinical trial of demcizumab (anti-DLL4, OMP-21M18) for the treatment of patients with first-line advanced-stage non-small cell lung cancer (NSCLC).
“Based on anti-tumor activity and the safety profile observed in our Phase 1b study of demcizumab plus standard-of-care in non-small cell lung cancer, we believe demcizumab has the potential to achieve meaningful clinical benefits for patients with this difficult cancer. We look forward to assessing, with the study investigators, demcizumab’s activity and safety in a randomized setting,” said Jakob Dupont, M.D., OncoMed’s Chief Medical Officer.
The Phase 2 “DENALI” trial is expected to enroll approximately 200 patients with first-line metastatic Stage IV non-squamous NSCLC whose tumors do not have an epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutation. Patients will be randomized into one of three study arms to compare the efficacy and safety of demcizumab combined with carboplatin and pemetrexed versus carboplatin and pemetrexed alone. In all three arms, patients will receive carboplatin and pemetrexed for four cycles, followed by pemetrexed maintenance. In addition, patients in Arm 1 will receive the chemotherapy plus placebo, patients in Arm 2 will receive chemotherapy with one truncated course of demcizumab every three weeks for four doses and patients in Arm 3 will receive chemotherapy with two truncated courses of demcizumab with the second truncated course starting at Day 168. The primary endpoint is progression-free survival. Secondary endpoints include response rate, duration of response, overall survival, safety, immunogenicity and pharmacokinetics. The DENALI study will also explore pharmacodynamics and several potential predictive biomarkers. DENALI will be conducted at approximately 60 sites in Europe, the United States and Australia.
“This is a major milestone for us, as it is the first of two randomized Phase 2 trials being conducted for demcizumab in our collaboration with Celgene, and the first anti-DLL4 antibody to enter this phase of development. Patient dosing for the second demcizumab randomized Phase 2 trial in pancreatic cancer should also begin shortly. Two additional Phase 2 trials are already underway for tarextumab, our anti-Notch2/3 antibody. Depending on each study’s rate of enrollment and other factors, we expect these four randomized Phase 2 studies to produce results in the 2016-2017 timeframe,” said Paul J. Hastings, OncoMed’s Chairman and Chief Executive Officer.
In OncoMed’s Phase 1b clinical study of demcizumab in NSCLC, the combination of demcizumab with pemetrexed and carboplatin was generally well tolerated. No moderate to severe cardiopulmonary adverse events occurred with truncated demcizumab administration. Of 33 patients evaluable for efficacy, one (3%) had a complete response, 15 (45%) had a partial response and 13 (39%) had stable disease per RECIST criteria for an overall clinical benefit rate of 88 percent. Among the 14 evaluable patients who received demcizumab on a truncated dosing schedule, one had a complete response, seven had a partial response, five achieved stable disease and one had progressive disease resulting in an overall clinical benefit rate in this subset of patients of 93 percent. Eight patients treated with demcizumab at or above the Phase 2 dose schedule had progression-free survival for greater than 300 days. Final clinical data from this Phase 1b trial are anticipated to be presented at a medical meeting in 2015.
About Non-Small Cell Lung Cancer
According to the American Cancer Society, lung cancer (both small cell and non-small cell) is the second most common cancer in men and women and is by far the leading cause of cancer death. Non-small cell lung cancer is expected to make up the vast majority of the 224,210 newly diagnosed cancer cases and the 159,260 cancer deaths estimated to occur in the U.S. in 20141. Forty percent of patients with newly diagnosed non-small cell lung cancer have Stage IV disease. Treatment options for these patients include chemotherapy with or without targeted agents (such as bevacizumab or EGFR inhibitors). For first-line non-squamous NSCLC, one of the preferred chemotherapy regimens is pemetrexed (Alimta(R)) with a platinum-based chemotherapy for four cycles, followed by pemetrexed maintenance.
About Demcizumab (anti-DLL4, OMP-21M18)
Demcizumab is a humanized monoclonal antibody that inhibits Delta-Like Ligand 4 (DLL4) in the Notch signaling pathway. Based on preclinical studies, demcizumab appears to have a multi-pronged mechanism of action: halting cancer stem cell growth and reducing CSC frequency, disrupting angiogenesis in the tumor and potentially augmenting anti-tumor immune response.
OncoMed has completed enrollment of two Phase 1b clinical studies of demcizumab plus standard-of-care in patients with first-line advanced pancreatic cancer and extensive stage non-squamous non-small cell lung cancer. A Phase 1b/2 trial of demcizumab and paclitaxel in patients with platinum-resistant ovarian cancer is also ongoing. Data of the Phase 1b studies of demcizumab in pancreatic cancer and NSCLC were presented in September 2014 at the European Society for Medical Oncology (ESMO) Congress in Madrid, Spain. These data showed that demcizumab was well tolerated in combination with standard-of-care therapies and use of a truncated dosing regimen of appeared to successfully mitigate risks of moderate-to-severe cardiopulmonary toxicities. In both Phase 1b studies, demcizumab demonstrated encouraging anti-tumor response rates.
Demcizumab is part of OncoMed’s collaboration with Celgene Corporation.
About OncoMed Pharmaceuticals
OncoMed Pharmaceuticals is a clinical-stage company focused on discovering and developing novel therapeutics targeting cancer stem cells (CSCs). OncoMed has six anti-cancer product candidates in clinical development, including demcizumab (anti-DLL4, OMP-21M18), tarextumab (anti-Notch2/3, OMP-59R5), anti-Notch1 (OMP-52M51), anti-DLL4/VEGF bispecific antibody (OMP-305B83), vantictumab (anti-FZD7, OMP-18R5), and ipafricept (FZD8-Fc, OMP-54F28), which each target key cancer stem cell signaling pathways including Notch and Wnt. OncoMed plans to file an Investigational New Drug application in early 2015 for anti-RSPO3 (OMP-131R10), an antibody targeting a third key cancer stem cell signaling pathway called R-spondin-LGR. OncoMed is also pursuing discovery of additional novel anti-CSC and cancer immunotherapy product candidates. OncoMed has formed strategic alliances with Celgene Corporation, Bayer Pharma AG and GlaxoSmithKline (GSK). Additional information can be found at the company’s website: www.oncomed.com.
SOURCE: OncoMed Pharmaceuticals
Post Views: 135
REDWOOD CITY, CA, USA I February 4, 2015 I OncoMed Pharmaceuticals, Inc. (OMED), a clinical-stage company developing novel therapeutics that target cancer stem cells (CSCs), or tumor-initiating cells, announced that patient dosing has begun in the double-blinded, placebo-controlled, randomized Phase 2 clinical trial of demcizumab (anti-DLL4, OMP-21M18) for the treatment of patients with first-line advanced-stage non-small cell lung cancer (NSCLC).
“Based on anti-tumor activity and the safety profile observed in our Phase 1b study of demcizumab plus standard-of-care in non-small cell lung cancer, we believe demcizumab has the potential to achieve meaningful clinical benefits for patients with this difficult cancer. We look forward to assessing, with the study investigators, demcizumab’s activity and safety in a randomized setting,” said Jakob Dupont, M.D., OncoMed’s Chief Medical Officer.
The Phase 2 “DENALI” trial is expected to enroll approximately 200 patients with first-line metastatic Stage IV non-squamous NSCLC whose tumors do not have an epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutation. Patients will be randomized into one of three study arms to compare the efficacy and safety of demcizumab combined with carboplatin and pemetrexed versus carboplatin and pemetrexed alone. In all three arms, patients will receive carboplatin and pemetrexed for four cycles, followed by pemetrexed maintenance. In addition, patients in Arm 1 will receive the chemotherapy plus placebo, patients in Arm 2 will receive chemotherapy with one truncated course of demcizumab every three weeks for four doses and patients in Arm 3 will receive chemotherapy with two truncated courses of demcizumab with the second truncated course starting at Day 168. The primary endpoint is progression-free survival. Secondary endpoints include response rate, duration of response, overall survival, safety, immunogenicity and pharmacokinetics. The DENALI study will also explore pharmacodynamics and several potential predictive biomarkers. DENALI will be conducted at approximately 60 sites in Europe, the United States and Australia.
“This is a major milestone for us, as it is the first of two randomized Phase 2 trials being conducted for demcizumab in our collaboration with Celgene, and the first anti-DLL4 antibody to enter this phase of development. Patient dosing for the second demcizumab randomized Phase 2 trial in pancreatic cancer should also begin shortly. Two additional Phase 2 trials are already underway for tarextumab, our anti-Notch2/3 antibody. Depending on each study’s rate of enrollment and other factors, we expect these four randomized Phase 2 studies to produce results in the 2016-2017 timeframe,” said Paul J. Hastings, OncoMed’s Chairman and Chief Executive Officer.
In OncoMed’s Phase 1b clinical study of demcizumab in NSCLC, the combination of demcizumab with pemetrexed and carboplatin was generally well tolerated. No moderate to severe cardiopulmonary adverse events occurred with truncated demcizumab administration. Of 33 patients evaluable for efficacy, one (3%) had a complete response, 15 (45%) had a partial response and 13 (39%) had stable disease per RECIST criteria for an overall clinical benefit rate of 88 percent. Among the 14 evaluable patients who received demcizumab on a truncated dosing schedule, one had a complete response, seven had a partial response, five achieved stable disease and one had progressive disease resulting in an overall clinical benefit rate in this subset of patients of 93 percent. Eight patients treated with demcizumab at or above the Phase 2 dose schedule had progression-free survival for greater than 300 days. Final clinical data from this Phase 1b trial are anticipated to be presented at a medical meeting in 2015.
About Non-Small Cell Lung Cancer
According to the American Cancer Society, lung cancer (both small cell and non-small cell) is the second most common cancer in men and women and is by far the leading cause of cancer death. Non-small cell lung cancer is expected to make up the vast majority of the 224,210 newly diagnosed cancer cases and the 159,260 cancer deaths estimated to occur in the U.S. in 20141. Forty percent of patients with newly diagnosed non-small cell lung cancer have Stage IV disease. Treatment options for these patients include chemotherapy with or without targeted agents (such as bevacizumab or EGFR inhibitors). For first-line non-squamous NSCLC, one of the preferred chemotherapy regimens is pemetrexed (Alimta(R)) with a platinum-based chemotherapy for four cycles, followed by pemetrexed maintenance.
About Demcizumab (anti-DLL4, OMP-21M18)
Demcizumab is a humanized monoclonal antibody that inhibits Delta-Like Ligand 4 (DLL4) in the Notch signaling pathway. Based on preclinical studies, demcizumab appears to have a multi-pronged mechanism of action: halting cancer stem cell growth and reducing CSC frequency, disrupting angiogenesis in the tumor and potentially augmenting anti-tumor immune response.
OncoMed has completed enrollment of two Phase 1b clinical studies of demcizumab plus standard-of-care in patients with first-line advanced pancreatic cancer and extensive stage non-squamous non-small cell lung cancer. A Phase 1b/2 trial of demcizumab and paclitaxel in patients with platinum-resistant ovarian cancer is also ongoing. Data of the Phase 1b studies of demcizumab in pancreatic cancer and NSCLC were presented in September 2014 at the European Society for Medical Oncology (ESMO) Congress in Madrid, Spain. These data showed that demcizumab was well tolerated in combination with standard-of-care therapies and use of a truncated dosing regimen of appeared to successfully mitigate risks of moderate-to-severe cardiopulmonary toxicities. In both Phase 1b studies, demcizumab demonstrated encouraging anti-tumor response rates.
Demcizumab is part of OncoMed’s collaboration with Celgene Corporation.
About OncoMed Pharmaceuticals
OncoMed Pharmaceuticals is a clinical-stage company focused on discovering and developing novel therapeutics targeting cancer stem cells (CSCs). OncoMed has six anti-cancer product candidates in clinical development, including demcizumab (anti-DLL4, OMP-21M18), tarextumab (anti-Notch2/3, OMP-59R5), anti-Notch1 (OMP-52M51), anti-DLL4/VEGF bispecific antibody (OMP-305B83), vantictumab (anti-FZD7, OMP-18R5), and ipafricept (FZD8-Fc, OMP-54F28), which each target key cancer stem cell signaling pathways including Notch and Wnt. OncoMed plans to file an Investigational New Drug application in early 2015 for anti-RSPO3 (OMP-131R10), an antibody targeting a third key cancer stem cell signaling pathway called R-spondin-LGR. OncoMed is also pursuing discovery of additional novel anti-CSC and cancer immunotherapy product candidates. OncoMed has formed strategic alliances with Celgene Corporation, Bayer Pharma AG and GlaxoSmithKline (GSK). Additional information can be found at the company’s website: www.oncomed.com.
SOURCE: OncoMed Pharmaceuticals
Post Views: 135
