OncoMed Pharmaceuticals has initiated a Phase Ib/II ovarian cancer trial of its anti-cancer stem cell product candidate, demcizumab (OMP-21M18), a humanised monoclonal antibody that inhibits Delta-Like Ligand 4 (DLL4) in the Notch signalling pathway.
The study, which is being partly funded under an ovarian cancer National Cancer Institute SPORE Grant Programme, will enrol patients at the MD Anderson Cancer Center in Houston, Texas, US.
During the Phase Ib/II trial, demcizumab will be tested in combination with paclitaxel in patients with platinum-resistant ovarian cancer, fallopian tube cancer or primary peritoneal cancer.
Upon completion of a Phase Ib safety run-in, a Phase II clinical study will be carried out in these patients.
According to the company, determination of the progression-free survival and response rate of the novel demcizumab with paclitaxel combination are the primary endpoints of the Phase II study, while overall survival, biomarker endpoints and safety are the key secondary and exploratory endpoints.
The University of Texas MD Anderson Cancer Center professor Robert Coleman said 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," Coleman said.
The trial is the company’s fourth Phase Ib trial of demcizumab, and the second portion of this protocol would represent the first Phase II trial.
MD Anderson Cancer Center professor Anil Sood added: "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."
The company’s Phase Ib trials combining demcizumab with chemotherapy regimens have been started in patients with first-line pancreatic cancer, first or second-line colorectal cancer and first-line non-small cell lung cancer (NSCLC).
The first study is in combination with standard-of-care gemcitabine and Abraxane in first-line advanced pancreatic cancer patients, and the second study is in combination with standard-of-care carboplatin and pemetrexed (Alimta) in first-line advanced NSCLC patients.
Patients are currently being enroled to carry out the Phase Ib trials for pancreatic cancer and non-small cell lung cancer.
OncoMed chief medical officer Jakob Dupont said: "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 1a single-agent study of demcizumab."
Cancer stem cells, or CSCs, are the subpopulation of cells in a tumour responsible for driving growth and metastasis of the tumour.
The common cancer drugs and chemotherapies currently available usually target bulk tumour cells but have negligible impact on CSCs, thereby providing a path for recurrence of the tumour.
OncoMed believes its product candidates are distinct from the current generations of chemotherapies and cancer drugs, as they target CSCs by blocking self-renewal and driving differentiation of CSCs toward a non-tumourigenic state, and also impact bulk tumour cells.
Image: Micrograph of a low malignant potential mucinous ovarian tumour. Photo: courtesy of Nephron.