Insights From: Martin H. Voss, MD, Memorial Sloan Kettering Cancer Center; Thomas Hutson, DO, PharmD, FACP, Baylor University Medical Center; Texas Oncology; James J. Hsieh, MD, PhD, Washington University School of Medicine
James J. Hsieh, MD, PhD: Vaccination is a very, very interesting concept in terms of how we are going to further improve the care. So, we have the many, many different mechanisms. Vaccination is a concept developed for humans against different viral infections. That’s what we did, we got our vaccination. But the problem is the vaccination, if you used the old definition of vaccination, it didn’t work that well in cancer because cancer is a heterogenous disease.
So, with billions of clones, how can you just design 1 thing to attack it and viruses in variants? Viruses have just only a few proteins, and they don’t change; that’s why it’s easy to develop a vaccination. But for cancer, if you want to develop a vaccine, it should be very, very specific. For the past 20 years, people have tried cancer vaccination, but it didn’t work that well because they missed the point of the heterogeneity. They focused on only a few genes and only a few commonly expressed, normal variants, or normal copy in your body, so it’s not going to work that well.
The vaccination has a long way to go, but there’s a great promise in terms of how to develop a vaccination. In my opinion, there are many, many ways of designing, personalizing the vaccine, and I think the vaccination should not be so one-off-the-shelf for everybody. It should be designed for individual patients. Figure out what kind of mutation they have in their tumor and figure out whether they express or not. And they can think about designing peptide or RNA or DNA to represent these specific mutations and express it into our immune system either through the in vitro culture on dendritic cells or just using the liposome-conjugated differential RNA or peptide and inject it.
I think vaccination is very, very important. The other treatment will be further improvement of the checkpoint inhibition, the immunotherapy, and not only just the checkpoint. It could be NK cells or many other things that should be involved. And on top of that, there’s a new area of metabolic drugs we’re taking a look at in kidney cancer. So, many things need to have happened.
Thomas Hutson, DO, PharmD, FACP: There is a clinical rationale to proceed with other immunologic types of therapy, such as vaccine strategies in kidney cancer. In order for a vaccine to be appropriate in kidney cancer, we need to overcome the innate resistance that occurs in this disease. As we’ve seen with the efficacy of I-O types of agents in this cancer, that can be overcome with some current strategies. It will be very interesting in the future, as we try to find antigens dependent on immune stimulators and try to launch them in kidney cancer, to see if we can improve the efficacy. So, I would imagine some type of an autologous tumor vaccine combined with some type of an immuno stimulator, such as an I-O agent, to be a path forward in a vaccine approach for this cancer.
Martin H. Voss, MD: Vaccine-based strategies have been investigated for the treatment of metastatic kidney cancer for some time now, and we have recently had updates for 2 pivotal trials in this space. The IMA901 multipeptide vaccine has been tested on a large phase III randomized trial in combination with sunitinib versus sunitinib alone. This is called the IMPRINT trial that was recently published by Brian Rini and his colleagues in Lancet Oncology. This was a negative phase III study in the frontline space, as this new combination vaccine plus TKI failed to show an improvement in overall survival over tyrosine kinase therapy with sunitinib alone.
There’s a second important trial that has been ongoing for some time, the so-called ADAPT trial. This is a now dendritic cell autologous vaccine where patients, through leukapheresis, actually collect dendritic cells and subsequently have their own tumor processed for an RNA-based vaccine of the dendritic cell rather than it being infused back into the patient. In the randomized phase III trial, the so-called ADAPT trial, this approach in combination with sunitinib and GMCSF was compared to sunitinib alone in the first-line setting.
We recently had a press release from the study’s sponsor telling us that in an interim analysis, the external data monitoring committee has recommended this study not be pursued further due to the fact that their interim analysis suggests that the primary endpoint of the study cannot be met, which would have been overall survival benefit for the vaccine-based approach compared to TKI alone.