CHICAGO, June 1, 2015 (GLOBE NEWSWIRE) -- OncoMed Pharmaceuticals Inc. (Nasdaq:OMED) presented new survival and biomarker data and updated clinical response and safety results from its Phase 1b clinical trial of tarextumab (anti-Notch2/3, OMP-59R5) in patients with first-line extensive-stage small cell lung cancer at the 2015 ASCO Annual Meeting. Dose-dependent anti-cancer activity for the combination of tarextumab and chemotherapy and acceptable safety profile were observed. In addition, the early data suggests those patients whose tumors had high Notch3 gene expression may achieve prolonged survival outcomes with tarextumab treatment.
"We are encouraged by the emerging safety and anti-cancer activity profile for tarextumab in the treatment of small cell lung cancer. In addition, we have initial data in a subset of high dose patients that Notch3 gene expression, which is associated with poor survival and chemo resistance in a number of solid tumors, may be a useful predictive biomarker for tarextumab treatment and survival in this difficult to treat cancer," said Paul J. Hastings, Chairman and Chief Executive Officer of OncoMed. "We look forward to exploring the findings from our Phase 1b trial further in the ongoing randomized Phase 2 PINNACLE clinical trial of tarextumab plus platinum-based therapy in patients with extensive-stage small cell lung cancer."
Data from the Phase 1b study of tarextumab were presented today by Dr. M. Catherine Pietanza, M.D., of Memorial Sloan-Kettering Cancer Center, during the Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers poster discussion session in a presentation titled "Final results of phase 1b of tarextumab (TRXT, OMP-59R5, anti-Notch2/3) in combination with etoposide and platinum (EP) in patients (pts) with untreated extensive-stage small-cell lung cancer (ED-SCLC)" (Abstract #7508). A copy of the poster is available on the OncoMed website.
Tarextumab in Small Cell Lung Cancer Phase 1b Results
The Phase 1b open-label study enrolled a total of 27 patients with extensive-stage small cell lung cancer who had not received prior treatment for extensive stage disease. Patients were treated on sequential dose escalation cohorts of tarextumab (5-15mg/kg) administered every three weeks with etoposide and either cisplatin or carboplatin (platinum-based therapy).
Tumor samples were collected from all patients enrolled in the study and a retrospective biomarker analysis was conducted to measure Notch3 gene expression as a predictive biomarker for efficacy. Notch3 overexpression is associated with poor survival and chemotherapeutic resistance in a number of solid tumors. A trend of longer survival was observed in patients whose tumors were identified as being Notch3 high and who were among the 11 patients in the higher dose cohorts (≥12.5 mg/kg). These preliminary data support OncoMed's hypothesis, developed from preclinical xenograft experiments that high Notch3 expression could be a predictive biomarker for tarextumab treatment in patients with small cell lung cancer. OncoMed's ongoing randomized Phase 2 PINNACLE trial has a primary endpoint assessing the outcome of Notch3 high patients treated with tarextumab versus placebo.
Of 26 patients evaluable for radiographic RECIST response, 20 (77%) achieved partial responses and six achieved stable disease for an overall clinical benefit rate of 100 percent. Greater tumor size reductions were observed among those patients who received doses of tarextumab at or above 12.5 mg/kg. The median progression-free and overall survival values for all 27 subjects were 4.4 months and 8.2 months, respectively.
Pharmacodynamic markers in plasma and whole blood samples demonstrated clear evidence of Notch pathway blockade, particularly at doses of 7.5 mg/kg and above. Suppression of key angiogenic growth factors was also observed.
The combination of tarextumab with chemotherapy was well tolerated up to 15 mg/kg. The most common drug-related adverse events were diarrhea, fatigue and nausea. These were primarily Grade 1 and 2 events, manageable with supportive care. Treatment with tarextumab did not appear to exacerbate side effects attributable to chemotherapy. A Phase 2 dose of tarextumab 15mg/kg every three weeks with etoposide and platinum-based therapy was selected with consideration to safety, pharmacodynamics, radiographic tumor reduction and potentially longer survival in biomarker positive patients.
"In the small cell lung cancer setting, we've observed evidence of dose-dependent anti-cancer activity for tarextumab in combination with chemotherapy with an acceptable safety profile. Further, the early data suggest that patients whose tumors have higher levels of Notch3 gene expression may achieve prolonged survival outcomes with tarextumab treatment. Taken together, these observations support our Phase 2 dose and trial design," said Jakob Dupont, M.D., Senior Vice President and Chief Medical Officer.
The enrollment of the randomized Phase 2 part of PINNACLE is ongoing at centers across the United States.
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 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. Small cell lung cancer is expected to make up about 10%-15% of the 224,210 newly diagnosed lung cancer cases and the 159,260 deaths estimated to occur in the U.S. in 20141. SCLC tends to grow and spread quickly, and is typically not discovered until it has metastasized to other parts of the body (extensive stage). The current standard of care in treating small cell lung cancer is the chemotherapeutic etoposide in combination with either cisplatin or carboplatin. In spite of a high sensitivity to chemotherapy and remission rates of up to 80 percent following initial treatment, the median overall survival is less than one year for patients with extensive stage disease2.
About Tarextumab (anti-Notch2/3, OMP-59R5)
Tarextumab (anti-Notch2/3, OMP-59R5) is a fully human monoclonal antibody that targets the Notch2 and Notch3 receptors. Preclinical studies have suggested that tarextumab exhibits two mechanisms of action: (1) by downregulating Notch pathway signaling, tarextumab appears to have anti-CSC effects, and (2) tarextumab affects pericytes, impacting stromal and tumor microenvironment. Tarextumab is currently being studied in two randomized Phase 2 clinical trials. The "ALPINE" study (Antibody therapy in first-Line Pancreatic cancer Investigating anti-Notch Efficacy and safety) is assessing tarextumab with Abraxane® (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine in first-line advanced pancreatic cancer patients. The "PINNACLE" study (A Phase 1b/2 Study of OMP-59R5 in Combination with Etoposide and Platinum Therapy in Subjects with Untreated Extensive Stage Small Cell Lung Cancer) is testing tarextumab in combination with etoposide and cisplatin and etoposide and carboplatin in first-line extensive stage small cell lung cancer patients. Tarextumab is part of OncoMed's collaboration with GlaxoSmithKline (GSK). GSK has an option to obtain an exclusive license to tarextumab during certain time periods through completion of the proof-of-concept Phase 2 trials.
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.
2 Jänne PA, Freidlin B, Saxman S, et al. Cancer 2002; 95:1528-38.
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 potential for prolonged survival outcomes with tarextumab treatment for small cell lung cancer patients with high Notch3 gene expression; and the usefulness of Notch3 gene expression as a predictive biomarker for tarextumab treatment and survival in small cell lung cancer. 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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