40% of Patients Receiving Continuous Dosing of Demcizumab plus Standard Chemotherapy Alive at Two Years
New Biomarker Data May Support Prolonged Survival Observations in Subset of Patients
Randomized Phase 2 DENALI Clinical Trial Currently Enrolling Patients
CHICAGO, June 1, 2015 (GLOBE NEWSWIRE) -- At the 2015 ASCO Annual Meeting, OncoMed Pharmaceuticals Inc. (Nasdaq:OMED) presented data from a Phase 1b study open-label trial of demcizumab plus carboplatin and pemetrexed (Alimta®) in patients with first-line advanced stage non-small cell lung cancer (NSCLC). Demcizumab is a first-in-class monoclonal antibody targeting DLL4 with anti-cancer stem cell, dysangiogenic and potential immune modulatory properties.
Patients enrolled in the multi-center Phase 1b study either received six cycles of pemetrexed and carboplatin with demcizumab administered every three weeks on a continuous dosing schedule or four cycles of pemetrexed and carboplatin with truncated dosing of demcizumab (i.e., up to 63 days) followed by pemetrexed maintenance. Kaplan-Meier curves for the continuous dose cohort reveal prolonged progression-free survival and overall survival in a subset of demcizumab-treated patients. Of 23 patients in the continuous dosing cohort, ten (approximately 40%) survived more than two years. In these ten patients who survived more than 300 days, represented in the tail on the Kaplan-Meier survival curve, there was a cumulative 21.8 years of patient follow-up beyond those 300 days, and among these ten patients, only two patient deaths occurred as of the February 26, 2015 data cut off. Survival data from patients treated with the truncated demcizumab dose regimen is less mature, although the Kaplan-Meier curve shows a similar trajectory as of the February 2015 cut-off date.
A retrospective analysis of patient tumor samples was conducted looking at a number of biomarkers related to demcizumab's mechanism of action, including tumor expression of the DLL4 protein, tumor expression of the programmed death receptor ligand-1 (PD-L1), and presence of immune cells within tumors, in order to identify potential predictive biomarkers for the apparent prolonged survival of certain patients treated with demcizumab. New data related to retrospective biomarker analysis of tumors show a potential correlation between an increased presence of tumor infiltrating lymphocytes (TILs) and improved survival. This finding could be associated with demcizumab's recently elucidated immune mechanism of action.
"The observation of a tail on the Phase 1b Kaplan-Meier survival curve suggests that there is prolonged survival for a subset of NSCLC patients treated with demcizumab. It is a provocative finding that about 40 percent of these patients are alive beyond two years," said Jakob Dupont, M.D., Senior Vice President and Chief Medical Officer. "Additionally, the biomarker data presented at ASCO suggest that in NSCLC demcizumab could augment patient anti-tumor immune response."
A total of 46 patients were enrolled in the Phase 1b study, with 40 evaluable for efficacy across both cohorts. One patient (3%) had a complete response, 19 (48%) had partial responses and 15 (38%) had stable disease as measured by RECIST criteria. The overall clinical benefit rate was 88 percent. The Kaplan-Meier estimated median progression-free survival for the continuous and truncated demcizumab patients using the on-study data were and 5.3 and 5.8 months, respectively. A worst-case analysis (to ensure that Kaplan-Meier estimates are not impacted by selective reporting) showed a median overall survival of 6.3 months for the continuous demcizumab cohort, and 8.1 months for the truncated dose patients.
The regimen of demcizumab-carboplatin-pemetrexed was generally well-tolerated with fatigue, nausea and manageable hypertension being the most common demcizumab-related toxicities. The truncated dosing regimen of demcizumab and patient monitoring appears to prevent the onset of reversible cardiopulmonary toxicities. Twenty-three patients were dosed at or above the Phase 2 dose of demcizumab (5mg/kg every 3 weeks) utilizing the truncated approach in the Phase 1b NSCLC trial and no moderate-to-severe cardiovascular toxicities occurred. Additionally, well over 60 patients from OncoMed's Phase 1b clinical studies in NSCLC, pancreatic and ovarian cancers have been treated with the truncated dosing approach with no occurrence of these cardiovascular events. The Phase 2 dose of demcizumab shows sustained pharmacodynamic modulation of the Notch pathway in patient samples. The randomized Phase 2 DENALI trial of demcizumab with carboplatin and pemetrexed in first-line non-squamous NSCLC is currently enrolling patients in Europe, Australia, and the United States.
Data from the Phase 1b NSCLC demcizumab clinical trial were presented at the 2015 ASCO Annual Meeting in a poster titled "A Phase 1b study of the anti-cancer stem cell agent demcizumab (DEM), pemetrexed (PEM) & carboplatin (CARBO) in patients with 1st line non-squamous NSCLC" (Abstract #8045) was presented by Dusan Kotasek MBBS, FRACP, Adelaide Cancer Centre. The poster presented during today's ASCO Annual Meeting is available on the OncoMed website.
Conference Call and Webcast to Review Data
OncoMed management will host a conference call and webcast for investors on Tuesday, June 2, 2015 at 7:00 a.m. EDT to discuss data presented at the 2015 ASCO Annual Meeting. To participate by telephone, please dial 855-420-0692 (Domestic) or 484-756-4194 (International). The conference ID number is 57579568. A live and archived audio webcast can be accessed through the Investors section of the Company's website at http://www.oncomed.com. The web broadcast of the conference call will be available for replay through July 2, 2015.
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 is conducting two randomized Phase 2 trials of demcizumab. The YOSEMITE trial is evaluating demcizumab and gemcitabine plus Abraxane in patients with first-line metastatic pancreatic cancers. The DENALI trial will assess the efficacy of demcizumab with carboplatin and pemetrexed in first-line non-squamous NSCLC. A Phase 1b/2 trial of demcizumab and paclitaxel in patients with platinum-resistant ovarian cancer is also ongoing.
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 cell (CSC) and immuno-oncology pathways. OncoMed has six anti-cancer product candidates in clinical development, the most advanced of which are in randomized Phase 2 clinical trials. Demcizumab (anti-DLL4, OMP-21M18), tarextumab (anti-Notch2/3, OMP-59R5), brontictuzumab (anti-Notch1, OMP-52M51), anti-DLL4/VEGF bispecific antibody (OMP-305B83), vantictumab (anti-FZD7, OMP-18R5), and ipafricept (FZD8-Fc, OMP-54F28) each target key cancer stem cell signaling pathways including Notch and Wnt. OncoMed recently filed an Investigational New Drug application 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 immuno-oncology 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.
To the extent that statements contained in this press release are not descriptions of historical facts regarding OncoMed Pharmaceuticals, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including OncoMed's expectations regarding the mechanism of action of demcizumab and its anti-cancer stem cell, dysangiogenesis, and potential immune modulatory properties; the potential for the combination of demcizumab (via continuous or truncated dosing) with pemetrexed and carboplatin to provide prolonged progression-free survival and overall survival in a subset of non-small cell lung cancer (NSCLC) patients; the correlation between an increased presence of tumor infiltrating lymphocytes (TILs) in tumors and the prolonged survival of certain NSCLC patients treated with demcizumab; the potential identification of predictive biomarkers for demcizumab treatment and prolonged survival in certain NSCLC patients; and the potential ability of demcizumab to augment anti-tumor immune responses in NSCLC patients. Such forward-looking statements involve substantial risks and uncertainties that could cause OncoMed's clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the preclinical and clinical development process. OncoMed undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to OncoMed's business in general, see OncoMed's Annual Report on Form 10-K for the fiscal year ended December 31, 2014, filed with the Securities and Exchange Commission (SEC) on March 12, 2015, and OncoMed's Quarterly Report on Form 10-Q for the fiscal quarter ended March 31, 2015, filed with the SEC on May 7, 2015.
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Source:OncoMed Pharmaceuticals, Inc.