ECC 2015

Multi-peptide vaccine for kidney cancer fails to improve survival

Dr Brian Rini - Cleveland Clinic Foundation, Cleveland, USA

Brian, tell me first of all about yourself and Cleveland Clinic, your lab, what you’re doing and everything.

I’m Brian Rini, I’m a medical oncologist from Cleveland Clinic and I do clinical and translational work in kidney cancer.

How did you get on to looking at this vaccine because you’re looking at a multi-peptide vaccine in kidney cancer, what are you doing?

This is, Immatics is the name of the company and they developed over many years this methodology for deriving peptides from tumour cells, peptides that are specific for tumour cells and not normal cells, and further testing their immunogenicity. So they basically came up with a cocktail of peptides that, when given to patients, are felt to generate a relevant anti-tumour immune response.

Metastatic renal cell cancer is a difficult one to tackle, isn’t it, with a vaccine?

It is, I mean it’s a tumour that’s considered immunogenic, like melanoma it has always had immunotherapy in the background, interleukin-2 was the first drug approved for that disease 25 years ago. Then came the wave of targeted therapies like sunitinib and now we’re turning back to immunotherapy.

Now you’ve been combining this therapy with sunitinib, what happened?

The trial looked at previously untreated metastatic kidney cancer patients, so this was their first therapy. They either got sunitinib alone which is a standard of care, it’s a VEGF receptor inhibitor, or they got sunitinib plus this vaccine. The concept was that sunitinib would provide disease control, the vaccine would provide an immune response. There’s also data to support that, sunitinib has favourable immunomodulatory activity so that it might actually make the vaccine work better.

So there was some hope that sunitinib might have helped the immune processes in a similar way to perhaps the checkpoint inhibition process do, or a different way but…

A different way but a similar result, a similar idea, yes, a similar concept. There are clinical and pre-clinical data that certain cell populations, certain immunosuppressive cell populations are reduced when patients are treated with sunitinib.

And what happened?

Unfortunately the trial did not show an overall survival benefit. There’s really no difference in survival among the arms. Both arms did extremely well, progression free survival was 15 months, which is very long, and overall survival was very long as well. So all the patients did well and the vaccine did not provide an additional advantage.

Where do you think this leaves multi-peptide vaccines in the context of renal cell carcinoma?

I think vaccines in all of oncology have struggled, not because they can’t generate an immune response but the quantity of that response has always been inadequate, inadequate enough to have clinical relevance. I think this trial re-demonstrates that. But now that there are checkpoint inhibitors, there are other inhibitors of molecules like OX40 etc., again there is renewed interest in immunotherapy. I think some of those molecules, some of those drugs in combination may revive vaccines to provide some specificity to the immune response.

So what should doctors take home from this now?

It’s not a new treatment option because there was no advantage. Again, sunitinib remains the standard of care. There’s a lot of development of immunotherapy in kidney cancer going on right now and so I think vaccines will continue to be explored. There are other trials out there including other large trials but we’re really waiting again for those newer immunotherapies to make an impact.