Southampton

The RiVa Trial  

This early-phase clinical trial is testing a ground breaking new method of treatment for lymphoma (cancer of the lymph glands) that could potentially change the way we treat this disease. RiVa is a trial that has been entirely conceived in Southampton, from bench to patient in just two-and-a-half years. The great majority of drugs take an average of ~12 years to enter the clinic. RiVa is looking into a new combination of two drugs to treat lymphoma – rituximab, which targets CD20-expressing cells (e.g. lymphoma cells), and varlilumab, which enhances the immune system’s anticancer activity by targeting CD27 (a marker on T cells).

This trial’s primary endpoints are safety and response rates, but it also incorporates a comprehensive translational plan. In general, it involves the collection of sequential tumour biopsies before and after treatment to allow analysis of protein markers (using multicolour flow cytometry) and gene expression (using next generation RNA sequencing). These experimental plans will be vital in helping us to determine the biomarkers that can tease out responders from non-responders. Further, in non-responders, it will also help us to elucidate the reasons for a lack of response and how we might overcome this. The majority of the analysis will be performed centrally at the Southampton ECMC WISH Laboratory.

The trial, funded by Cancer Research UK and the Celldex Therapeutics (NJ, USA) is in its early stages. The trial is being managed by the SCTU, and run in three ECMC centres in the UK: Southampton, Oxford and Manchester; as well as at Derriford Hospital, Plymouth. The trial is being conducted on patients who have relapsed or refractory lymphoma. The RiVa trial in collaboration with the Cancer Sciences Unit, Centre of Cancer Immunology, ECMC WISH Lab, Faculty of Medicine and sponsored by University Hospital Southampton NHS Foundation Trust.

“This is an exciting time for immunotherapy. We’ve always known that the immune system is capable of attacking cancer cells, but it is only in the last 10-20 years that we have been able to demonstrate this in patients. The antibody combinations tested here are extremely effective in preclinical studies and it will be really interesting to see if this is effective in patients. This trial is also designed in such a way that if we do not see the responses anticipated, we should have the necessary information to move forward therapeutically.” Said Dr Sean Lim, Antibody & Vaccine Group, Centre for Cancer Immunology, Southampton.