First Presentation of First-in-Human Trial of Anti-Notch1 (OMP-52M51) Suggests This Antibody Can be Given Safely With Early Suggestion of Efficacy in Patients With Certain Advanced Solid Tumors
Demcizumab (Anti-DLL4) Can be Safely Combined With Gemcitabine Chemotherapy for Pancreatic Cancer With Encouraging Early Efficacy Data
First Presentation of First-in-Human Trial of Frizzled8 Fusion Protein (OMP-54F28) Suggests the Drug Candidate Can be Safely Given With Evidence of Wnt-Pathway Targeting and Early Suggestion of Efficacy in Patients With Certain Advanced Solid TumorsClinical Pharmacodynamic Data for First-in-Class Anti-Frizzled Antibody Vantictumab Demonstrate Modulation of the Wnt Pathway in Tumors and Surrogate Tissues REDWOOD CITY, Calif., Oct. 21, 2013 (GLOBE NEWSWIRE) -- OncoMed Pharmaceuticals, Inc. (Nasdaq:OMED), a clinical-stage company developing novel therapeutics that target cancer stem cells (CSCs), or tumor-initiating cells, today reported data for four of its five clinical-stage programs at poster sessions 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. Anti-Notch1 Poster Dr. Lindsey Davis, from the University of Colorado-Denver, Aurora, CO, presented the first public unveiling of the first-in-human Phase 1a data for OMP-52M51, a first-in-class anti-Notch1 antibody [ Poster B48, 'A first-in-human Phase 1 study of the novel cancer stem cell (CSC) targeting antibody OMP-52M51 (anti-Notch1) administered intravenously to patients with certain advanced solid tumors']. OMP-52M51 has been well tolerated thus far with the main target-mediated toxicity of diarrhea. Other related adverse events have included nausea, fatigue and rash. There is biomarker evidence of circulating tumor cell reduction with OMP-52M51 treatment, as well as early potential efficacy in two subjects, one with metastatic colorectal cancer and one with metastatic HER2 negative breast cancer. Dose escalation is continuing, and an expansion cohort for patients with tumors that have Notch1 activation is planned. Demcizumab (anti-DLL4) Poster Dr. Antonio Cubillo from START-Madrid, Madrid, Spain, presented Phase 1b data in pancreatic cancer for demcizumab, a humanized monoclonal antibody that inhibits Delta-Like Ligand 4 (DLL4) in the Notch signaling pathway [ Poster B78, 'A Phase Ib study of demcizumab (DEM, anti-DLL4) with gemcitabine (GEM) in patients with first-line locally advanced or metastatic pancreatic cancer']. The combination of demcizumab and gemcitabine was generally well tolerated. The most common demcizumab-related adverse events were: fatigue, manageable hypertension, nausea and vomiting. Observed toxicities were consistent with the single-agent safety profiles, and no new safety signals emerged. Demcizumab-related reversible cardiotoxicity appeared to be successfully prevented and managed through regular monitoring, a truncated treatment approach and cardioprotective medication, if indicated. The efficacy data from the study suggested early efficacy with a RECIST partial response rate of 25% and a stable disease rate of 44% for an overall clinical benefit rate of 69% for patients receiving demcizumab and gemcitabine across the dose cohorts. The cohort of patients receiving demcizumab at 5mg/kg every 3 weeks with gemcitabine had a median progression-free survival of 176 days. The combination of demcizumab (dosed in a truncated fashion to day 70) with gemcitabine and nab-paclitaxel is currently being evaluated in this trial, and a randomized Phase 2 trial in first-line stage IV pancreatic cancer is planned for 2014. FZD8-Fc Poster Dr. David Smith from University of Michigan, Ann Arbor, MI, presented the first public presentation of the first-in-human Phase 1a trial for OMP-54F28 (FZD8-Fc), a first-in-class fusion protein [ Poster B79, 'A first-in-human Phase 1 study of anti-cancer stem cell (CSC) agent OMP-54F28 (FZD8-Fc) targeting the WNT pathway in patients with advanced solid tumors']. OMP-54F28 consists of part of the Frizzled8 receptor fused to the Fc domain of a human IgG1 antibody. The drug product inhibits the Wnt pathway by binding Wnt ligand. In the ongoing Phase 1a trial, OMP-54F28 was administered to refractory solid tumor patients. The drug product was well tolerated, and dose escalation continues. The most common OMP-54F28 related adverse events were: decreased appetite, muscle spasms, nausea, and dysgeusia (altered taste sensation). There were rare changes in bone turnover markers that were easily managed with the bone risk mitigation plan on the study. Biomarker evaluations revealed Wnt pathway modulation with OMP-54F28 treatment in patient hair follicles. Potential early efficacy manifested by prolonged disease control was noted in two patients with Desmoid Tumors and a patient each with renal cell and pancreatic cancer. The clinical data enable initiation of three Phase 1b trials in late 2013 to early 2014. Vantictumab Biomarker Poster Dr. Ann Kapoun, Vice President of Translational Medicine at OncoMed, presented pharmacodynamic biomarker data for the first-in-human Phase 1a trial of vantictumab (OMP-18R5), a first-in-class anti-Frizzled antibody targeting the Wnt pathway [ Poster B24, 'Biomarker analysis in the first-in-human Phase 1a study for vantictumab (OMP-18R5; anti-Frizzled) demonstrates pharmacodynamic (PD) modulation of the Wnt pathway in patients with advanced solid tumors']. Pharmacodynamic effects of vantictumab were observed in tumor biopsies, hair follicles and blood. The effects were consistent with inhibition of the Wnt pathway, were observed starting at a dose of 0.5 mg/kg and extended beyond serum exposure. Dr. Jakob Dupont, OncoMed's Chief Medical Officer, commented, "All five of OncoMed's clinical programs are successfully moving toward the next stages of development. The trials are revealing that these novel anti-cancer stem cell product candidates have distinct safety profiles. We are also seeing biomarker evidence of key CSC pathway modulation and potentially early signs of efficacy in patients. It is particularly exciting that we have now have evidence from two Phase 1b trials that demcizumab can be safely combined with chemotherapy."