OncoMed Pharmaceuticals Inc., a clinical-stage company developing novel therapeutics that target cancer stem cells (CSCs), has presented safety and efficacy data from a Phase 1b clinical trial assessing the efficacy and safety of demcizumab (anti-DLL4, OMP-21M18) in non-small cell lung cancer (NSCLC) at the European Society for Medical Oncology (ESMO) 2014 Congress in Madrid, Spain.
Demcizumab is a monoclonal antibody that specifically blocks the key Notch signaling pathway in cancer stem cells, while selectively targeting Delta-like ligand 4 (DLL4), an activator of the Notch signaling pathway known to play a crucial role in cancer stem cells and cancer.
The results from this trial have shown that demcizumab together with standard-of-care chemotherapy was generally well tolerated, with favorable tumor response rates in patients receiving demcizumab plus pemetrexed and carboplatin for the first-line treatment of Stage III/IV NSCL.
Of the 33 patients who were assessed for efficacy, 3% had a complete response, 45% has a partial response and 39% had accomplished stable disease.
The overall clinical benefit rate was 88%, and 8 patients who were treated with demcizumab once every three weeks at doses of 5mg/kg or 7.5mg/kg plus the chemotherapeutic agents have remained progression free for more than 300 days.
“As we advance to Phase 2 clinical trials of demcizumab, we have successfully identified strategies that result in both favorable tolerability and compelling response rates. To date, sixty-four patients have been enrolled and treated on the demcizumab truncated dosing schedule that will be used in our randomized Phase 2 studies. The majority of these patients have now been followed for greater than 100 days without any moderate-to-severe cardiopulmonary toxicities and a number of patients remain on treatment,” Jakob Dupont, M.D., OncoMed’s Chief Medical Officer said in a company press release.
Additional data was also presented on the efficacy of demcizumab for the treatment of pancreatic cancer, where the combination therapy of demcizumab and gemcitabine, with or without nab-paclitaxel, was well tolerated by patients.
“Based on the data generated from our Phase 1b studies in pancreatic and non-small cell lung cancer we have identified a dosing regimen with impressive anti-tumor activity and an acceptable safety profile. We have confidence that these data enable the advancement of both programs into planned randomized Phase 2 studies in pancreatic cancer and NSCLC. Results from our Phase 1b demcizumab program not only signal the potential safety and anti-tumor activity for this drug, but also provide encouragement for the potential of an anti-cancer stem cell hypothesis,” Paul J. Hastings, Chairman and Chief Executive Officer added in the press release.