OncoMed Pharmaceuticals, Inc., a clinical-stage company developing novel therapeutics that target cancer stem cells (CSCs), or tumour-initiating cells, has started a phase Ib/II clinical trial of its anti-cancer stem cell product candidate, demcizumab (OMP-21M18) in ovarian cancer. The trial will enroll patients at the MD Anderson Cancer Centre in Texas. It is being funded in part under an ovarian cancer National Cancer Institute SPORE Grant Programme.

In this phase Ib/II trial, demcizumab is being tested in combination with paclitaxel in patients with platinum-resistant ovarian cancer, fallopian tube cancer or primary peritoneal cancer.  Following a phase Ib safety run-in, a phase II clinical trial will proceed in these patients. The primary endpoints of the phase II part of the trial will be to determine the progression-free survival and response rate of the novel demcizumab with paclitaxel combination. Key secondary and exploratory endpoints include overall survival, biomarker endpoints and safety.

Dr Robert Coleman, professor & vice chair, Clinical Research, Department of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Centre and the Principal Investigator who treated the first patient on the study noted, "Women with platinum-resistant ovarian, fallopian tube and primary peritoneal cancers are in need of new treatment options. We believe that an investigational therapy such as demcizumab, with its novel anti-cancer stem cell mechanism of action, could yield important results for these patients."

"The trial includes a number of translational science and biomarker evaluations that will help to elucidate the mechanisms by which demcizumab works for the treatment of ovarian cancer patients and aims to identify predictors of response to therapy," said Dr Anil Sood, professor & vice chair, Translational Research in the Department, who will be working on the trial.

The trial is OncoMed's fourth phase Ib trial of demcizumab, and the second portion of this protocol would represent the first phase II trial of demcizumab. Previous phase Ib trials combining demcizumab with chemotherapy regimens have been initiated in patients with first-line pancreatic cancer (with gemcitabine and Abraxane), first- or second-line colorectal cancer (with FOLFIRI chemotherapy) and first-line non-small cell lung cancer (with carboplatin and pemetrexed chemotherapy). The phase Ib trials in pancreatic cancer and non-small cell lung cancer are currently enrolling patients.

"We believe ovarian cancer is another important cancer indication for the demcizumab clinical programme and an area of high unmet medical need," said Dr Jakob Dupont, chief medical officer of OncoMed. "We have observed strong preclinical efficacy of demcizumab and paclitaxel in patient-derived ovarian cancer xenograft models, as well as early evidence of activity of demcizumab in ovarian cancer in the phase Ia single-agent study of demcizumab."

Paul Hastings, chairman and chief executive officer of OncoMed, emphasized, "The ovarian cancer trial provides the earliest opportunity to advance a demcizumab programme to phase II. As such it will represent a significant advance for this unpartnered anti-cancer stem cell asset."

Demcizumab (OMP-21M18) is a humanized monoclonal antibody that inhibits Delta-Like Ligand 4 (DLL4) in the Notch signaling pathway. Two phase Ib combination trials of demcizumab are ongoing. The first trial is in combination with standard-of care gemcitabine and Abraxane in first-line advanced pancreatic cancer patients, and the second trial is in combination with standard of care carboplatin and pemetrexed (Alimta) in first-line advanced non-small cell lung cancer (NSCLC) patients. OncoMed has worldwide rights to this programme.