US-based OncoMed Pharmaceuticals has started its Phase Ib trial of investigational agent demcizumab (anti-DLL4, OMP-21M18) in combination with Merck’s anti-programmed cell death 1 (PD1) therapy pembrolizumab (Keytruda) to treat advanced or metastatic solid tumours.
The combination could act as a double blockade for cancer-induced immune suppression, and have potential applications for solid cancers.
Patients will receive escalating doses of demcizumab and an approved dose of pembrolizumab.
The company noted that after an optimal combination dose is established, three expansion studies will begin for non-small cell lung cancer (NSCLC), anti-PD1 refractory solid tumours and castrate-resistant prostate cancer.
The trial’s primary objective is to determine the safety and tolerability of the demcizumab-pembrolizumab combination.
It will also look at comparative pharmacokinetic profiles, antibody activity against demcizumab or pembrolizumab, biomarker and immunological response, response rates and survival outcome in patients with advanced solid tumours, NSCLC, castrate-resistant prostate cancer and anti-PD1 antibody refractory cancers.
OncoMed chief medical officer Dr Jakob Dupont said: "We’ve designed the Phase Ib study to investigate the safety profile for the demcizumab and pembrolizumab combination and to look for signals of immunological, biomarker and anti-tumour activity in advanced solid tumours.
"Based on our preclinical studies, we believe demcizumab may have a distinctive immune modulatory effect of decreasing monocytic myeloid-derived suppressor cells, or MDSCs, within patient tumours.
"MDSCs are important cells that prevent a patient’s immune system from fighting their cancer, even in the setting of the new anti-PD1 treatments.
"In our preclinical studies, we have observed synergistic anti-tumor activity when combining anti-DLL4 and anti-PD1, which we attribute to their complementary mechanisms. We look forward to testing this novel combination in the clinic with the study investigators."
The trial will be conducted at several sites in the US and UK, including Memorial Sloan Kettering Cancer Center, Columbia University, START Center for Cancer Care, University of Michigan Medical Center, Sarah Cannon Research Institute, University of California San Francisco, Rocky Mountain Cancer Centers and The Royal Marsden Hospital.
Last year, the company reported on the impact of an anti-DLL4 and anti-PD1 on antitumour immune responses in preclinical studies.
Currently, demcizumab is being studied in two randomised Phase II clinical trials YOSEMITE and DENALI.
The agent has been developed as part of OncoMed’s collaboration with Celgene.