Safety Profile of Novel Combination Consistent With Known Toxicities of Demcizumab and Chemotherapy; No New Safety Signals
Early Evidence of Activity Noted With the Combination in Terms of Tumor Response Rate and Prolonged Disease Control
OncoMed Planning for Randomized Phase 2 Study in First-Line Advanced NSCLC in 2014
REDWOOD CITY, CA, USA I October 20, 2013 I OncoMed Pharmaceuticals, Inc. (OMED), a clinical-stage company developing novel therapeutics that target cancer stem cells (CSCs), or tumor-initiating cells, today reported updated Phase 1b data for demcizumab (OMP-21M18, Anti-DLL4), a monoclonal antibody targeting the Notch pathway, with carboplatin and pemetrexed in patients with first-line, stage IIIb/IV non-small cell lung cancer (NSCLC). The update was presented at a poster session at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, October 19-23, 2013, at the Hynes Convention Center in Boston, MA. Based on the data, OncoMed is planning to initiate a randomized Phase 2 trial of demcizumab with carboplatin and pemetrexed in first-line NSCLC in 2014.
In the ongoing Phase 1b clinical trial, 30 patients who had not received prior chemotherapy for their stage IIIb or IV NSCLC were treated with demcizumab, pemetrexed and carboplatin. The combination therapy was generally well tolerated with nausea, fatigue and hypertension being the most common related toxicities. Truncated dosing (i.e., limiting the duration of therapy to 63 days), monitoring with BNP and administering cardioprotective agents, if indicated, are being utilized in the current dose cohorts to maximize the therapeutic index and minimize potential cardiopulmonary toxicity.
Other results presented include:
- Nine of the 23 (39%) evaluable patients had a partial response.
- 48% of evaluable patients had stable disease for an overall clinical benefit rate of 87%.
- Three patients in the cohort of patients receiving demcizumab at 5mg/kg every 3 weeks were progression-free for more than 480 days.
- The median progression free survival for the cohort of 19 patients receiving demcizumab at 5mg/kg was 160 days.
- Truncated demcizumab dosing at 7.5mg/kg every 3 weeks for 63 days is ongoing.
The poster, entitled ‘A Phase 1b study of demcizumab plus pemetrexed and carboplatin in patients with 1st line stage IIIb/IV non-squamous non-small cell lung cancer (NSCLC),’ was presented by Dr. Jakob Dupont, Chief Medical Officer of OncoMed Pharmaceuticals, on behalf of the principal investigators (Dr. M. McKeage, University of Auckland, Auckland, New Zealand; Dr. D. Kotasek, Adelaide Cancer Centre, Adelaide, Australia; Dr. B. Markman, Monash Medical Centre, Monash University, Melbourne, Australia; Dr. M. Millward, Sir Charles Gairdner Hospital, Perth, Australia; Dr. M. Hidalgo, CNIO-CIOCC-START, Madrid, Spain; Dr. M. Jameson, Waikato Hospital, Hamilton, New Zealand; Dr. D. Harris, Christchurch Hospital, Christchurch, New Zealand; and Dr. B. Hughes, The Royal Brisbane and Woman Hospital, Brisbane, Australia), and the entire study team.
Dr. Dupont stated, “The Phase 1b combination data for demcizumab in NSCLC provide a clear path to a randomized Phase 2 study. Our careful studies of demcizumab’s safety profile have enabled us to institute an effective risk mitigation plan. Even though preliminary, the early efficacy data are intriguing.”
Paul J. Hastings, Chairman and Chief Executive Officer of OncoMed, commented, “We are encouraged to present these updated Phase Ib data on demcizumab, one of five lead clinical programs discovered and developed by OncoMed, and we look forward to advancing this drug to a randomized Phase 2 trial in NSCLC in 2014.”
About Cancer Stem Cells
Cancer stem cells, or CSCs, are the subpopulation of cells in a tumor responsible for driving growth and metastasis of the tumor. CSCs, also known as tumor-initiating cells, exhibit certain properties which include the capacity to divide and give rise to new CSCs via a process called self-renewal and the capacity to differentiate or change into the other cells that form the bulk of the tumor. Common cancer drugs target bulk tumor cells but have limited impact on CSCs, thereby providing a path for recurrence of the tumor. OncoMed’s product candidates target CSCs by blocking self-renewal and driving differentiation of CSCs toward a non-tumorigenic state, and also impact bulk tumor cells. OncoMed believes its product candidates are distinct from the current generations of chemotherapies and targeted therapies, and have the potential to significantly impact cancer treatment and the clinical outcome of patients with cancer.
About Demcizumab (OMP-21M18)
Demcizumab (OMP-21M18) is a humanized monoclonal antibody that inhibits Delta-Like Ligand 4 (DLL4) in the Notch signaling pathway. Two Phase 1b combination trials of demcizumab are ongoing. The first trial is in combination with standard-of-care gemcitabine and Abraxane(TM) in first-line advanced pancreatic cancer patients, and the second trial is in combination with standard-of-care carboplatin and pemetrexed (Alimta(TM)) in first-line advanced non-small cell lung cancer (NSCLC) patients. Data from the demcizumab pancreatic cancer Phase 1b trials will be presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston, MA, in October 2013. In addition, a Phase 1b/2 trial of demcizumab and paclitaxel in patients with platinum-resistant ovarian cancer is ongoing at MD Anderson Cancer Center. OncoMed has worldwide rights to this program.
About OncoMed Pharmaceuticals
OncoMed Pharmaceuticals Inc. (OMED), is a clinical-stage company focused on discovering and developing novel therapeutics targeting cancer stem cells (CSCs). OncoMed has five anti-cancer product candidates in clinical development, including demcizumab (Anti-DLL4, OMP-21M18), OMP-59R5 (Anti-Notch2/3), OMP-52M51 (Anti-Notch1), vantictumab (Anti-Fzd7, OMP-18R5), and OMP-54F28 (Fzd8-Fc), which target key CSC signaling pathways including Notch and Wnt. OncoMed has two other antibodies in preclinical development with Investigational New Drug filings planned as early as 2014. OncoMed is also pursuing discovery of additional novel anti-CSC product candidates. OncoMed has formed strategic alliances with Bayer Pharma AG and GlaxoSmithKline (GSK). Additional information can be found at the company’s website: www.oncomed.com.
SOURCE: OncoMed Pharmaceuticals
Post Views: 20
Safety Profile of Novel Combination Consistent With Known Toxicities of Demcizumab and Chemotherapy; No New Safety Signals
Early Evidence of Activity Noted With the Combination in Terms of Tumor Response Rate and Prolonged Disease Control
OncoMed Planning for Randomized Phase 2 Study in First-Line Advanced NSCLC in 2014
REDWOOD CITY, CA, USA I October 20, 2013 I OncoMed Pharmaceuticals, Inc. (OMED), a clinical-stage company developing novel therapeutics that target cancer stem cells (CSCs), or tumor-initiating cells, today reported updated Phase 1b data for demcizumab (OMP-21M18, Anti-DLL4), a monoclonal antibody targeting the Notch pathway, with carboplatin and pemetrexed in patients with first-line, stage IIIb/IV non-small cell lung cancer (NSCLC). The update was presented at a poster session at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, October 19-23, 2013, at the Hynes Convention Center in Boston, MA. Based on the data, OncoMed is planning to initiate a randomized Phase 2 trial of demcizumab with carboplatin and pemetrexed in first-line NSCLC in 2014.
In the ongoing Phase 1b clinical trial, 30 patients who had not received prior chemotherapy for their stage IIIb or IV NSCLC were treated with demcizumab, pemetrexed and carboplatin. The combination therapy was generally well tolerated with nausea, fatigue and hypertension being the most common related toxicities. Truncated dosing (i.e., limiting the duration of therapy to 63 days), monitoring with BNP and administering cardioprotective agents, if indicated, are being utilized in the current dose cohorts to maximize the therapeutic index and minimize potential cardiopulmonary toxicity.
Other results presented include:
- Nine of the 23 (39%) evaluable patients had a partial response.
- 48% of evaluable patients had stable disease for an overall clinical benefit rate of 87%.
- Three patients in the cohort of patients receiving demcizumab at 5mg/kg every 3 weeks were progression-free for more than 480 days.
- The median progression free survival for the cohort of 19 patients receiving demcizumab at 5mg/kg was 160 days.
- Truncated demcizumab dosing at 7.5mg/kg every 3 weeks for 63 days is ongoing.
The poster, entitled ‘A Phase 1b study of demcizumab plus pemetrexed and carboplatin in patients with 1st line stage IIIb/IV non-squamous non-small cell lung cancer (NSCLC),’ was presented by Dr. Jakob Dupont, Chief Medical Officer of OncoMed Pharmaceuticals, on behalf of the principal investigators (Dr. M. McKeage, University of Auckland, Auckland, New Zealand; Dr. D. Kotasek, Adelaide Cancer Centre, Adelaide, Australia; Dr. B. Markman, Monash Medical Centre, Monash University, Melbourne, Australia; Dr. M. Millward, Sir Charles Gairdner Hospital, Perth, Australia; Dr. M. Hidalgo, CNIO-CIOCC-START, Madrid, Spain; Dr. M. Jameson, Waikato Hospital, Hamilton, New Zealand; Dr. D. Harris, Christchurch Hospital, Christchurch, New Zealand; and Dr. B. Hughes, The Royal Brisbane and Woman Hospital, Brisbane, Australia), and the entire study team.
Dr. Dupont stated, “The Phase 1b combination data for demcizumab in NSCLC provide a clear path to a randomized Phase 2 study. Our careful studies of demcizumab’s safety profile have enabled us to institute an effective risk mitigation plan. Even though preliminary, the early efficacy data are intriguing.”
Paul J. Hastings, Chairman and Chief Executive Officer of OncoMed, commented, “We are encouraged to present these updated Phase Ib data on demcizumab, one of five lead clinical programs discovered and developed by OncoMed, and we look forward to advancing this drug to a randomized Phase 2 trial in NSCLC in 2014.”
About Cancer Stem Cells
Cancer stem cells, or CSCs, are the subpopulation of cells in a tumor responsible for driving growth and metastasis of the tumor. CSCs, also known as tumor-initiating cells, exhibit certain properties which include the capacity to divide and give rise to new CSCs via a process called self-renewal and the capacity to differentiate or change into the other cells that form the bulk of the tumor. Common cancer drugs target bulk tumor cells but have limited impact on CSCs, thereby providing a path for recurrence of the tumor. OncoMed’s product candidates target CSCs by blocking self-renewal and driving differentiation of CSCs toward a non-tumorigenic state, and also impact bulk tumor cells. OncoMed believes its product candidates are distinct from the current generations of chemotherapies and targeted therapies, and have the potential to significantly impact cancer treatment and the clinical outcome of patients with cancer.
About Demcizumab (OMP-21M18)
Demcizumab (OMP-21M18) is a humanized monoclonal antibody that inhibits Delta-Like Ligand 4 (DLL4) in the Notch signaling pathway. Two Phase 1b combination trials of demcizumab are ongoing. The first trial is in combination with standard-of-care gemcitabine and Abraxane(TM) in first-line advanced pancreatic cancer patients, and the second trial is in combination with standard-of-care carboplatin and pemetrexed (Alimta(TM)) in first-line advanced non-small cell lung cancer (NSCLC) patients. Data from the demcizumab pancreatic cancer Phase 1b trials will be presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston, MA, in October 2013. In addition, a Phase 1b/2 trial of demcizumab and paclitaxel in patients with platinum-resistant ovarian cancer is ongoing at MD Anderson Cancer Center. OncoMed has worldwide rights to this program.
About OncoMed Pharmaceuticals
OncoMed Pharmaceuticals Inc. (OMED), is a clinical-stage company focused on discovering and developing novel therapeutics targeting cancer stem cells (CSCs). OncoMed has five anti-cancer product candidates in clinical development, including demcizumab (Anti-DLL4, OMP-21M18), OMP-59R5 (Anti-Notch2/3), OMP-52M51 (Anti-Notch1), vantictumab (Anti-Fzd7, OMP-18R5), and OMP-54F28 (Fzd8-Fc), which target key CSC signaling pathways including Notch and Wnt. OncoMed has two other antibodies in preclinical development with Investigational New Drug filings planned as early as 2014. OncoMed is also pursuing discovery of additional novel anti-CSC product candidates. OncoMed has formed strategic alliances with Bayer Pharma AG and GlaxoSmithKline (GSK). Additional information can be found at the company’s website: www.oncomed.com.
SOURCE: OncoMed Pharmaceuticals
Post Views: 20
