UK-based biotechnology firm PsiOxus Therapeutics has started a combination trial of its lead product, enadenotucirev, with Merck’s Keytruda (pembrolizumab), in patients with carcinomas.
The study of pembrolizumab in combination with enadenotucirev (SPICE) trial will evaluate the safety and efficacy of the combination therapy.
PsiOxus’ enadenotucirev is an oncolytic virus that selectively infects cancer cells when administered by intravenous infusion.
The trial will assess enadenotucirev’s ability to reverse resistance to checkpoint inhibitors for certain tumour types, including metastatic colorectal cancer.
The study will involve several US clinical centres, and conclude in 2017.
PsiOxus CEO Dr John Beadle said: "Although checkpoint inhibitors represent a tremendous breakthrough in immunotherapy, the majority of tumours are currently resistant to these agents. More than 90% of colorectal tumours, for example, are currently regarded as checkpoint resistant.
"We aim to show that a combination of enadenotucirev with pembrolizumab can reverse that resistance and significantly open up the market for checkpoint inhibitors and enadenotucirev, for the very important benefit of patients."
The ability to deliver enadenotucirev systemically via intravenous infusion represents a significant advantage over other oncolytic therapies, such as Imlygic (T-vec), that require intra-tumoural delivery.
Phase I clinical trials have shown that enadenotucirev’s selective infection of cells is associated with the infiltration of immune cells (T-cells) into colorectal tumours.
Pre-clinical trials have demonstrated that the virus can directly stimulate immune cell activity, and that this stimulation synergises with checkpoint inhibitor activity.
PsiOxus has already developed enadenotucirev-based viruses, which are capable of producing a wide range of functioning therapeutic antibodies, including anti-PDL1 and anti-CTLA4, in preclinical studies.