Melanoma immunotherapy latest and TVEC plus pembrolizumab

Dr Georgina Long - University of Sydney, Sydney, Australia

Georgina, you’re based down in Sydney, tell me a little bit about your job and then I’ll get on with asking you about MASTERKEY265. What are you doing down there?

I’m a medical oncologist, I’m also a translational researcher and have a large translational research programme. I’m at Melanoma Institute Australia and the University of Sydney and I treat patients with melanoma.

Importantly you’re looking at checkpoint inhibition, but not only that, you’re adding another component to it, another immunotherapy component. Could you tell me about the MASTERKEY265 study and what it involves?

Sure, it’s a phase Ib study, we are opening a phase III part to it later this year. But I’m presenting the phase Ib portion of that study at the European Congress this year.

And you’re looking at melanoma, of course.

Melanoma patients. We’ve been using immunotherapies for quite a while in melanoma and we’ve had great success, firstly with ipilimumab, secondly with the anti-PD1 pembrolizumab and nivolumab and we’re now looking at combination strategies. We’ve already combined anti-PD1 with ipilimumab and saw fantastic results with that; we’re now looking at combinations, for example in this study TVEC plus the anti-PD1 pembrolizumab.

Tell me about TVEC, what it is.

TVEC is a genetically modified virus, herpes simplex virus 1. The virulence factors have been removed from it so that it replicates specifically in tumour cells. When it replicates it releases a lot of tumour derived antigen which helps activate the T-cells. In the genetically modified virus we also have a little cassette of GTSF and that stimulates the antigen presentation. The hope is that when you combine anti-PD1 with TVEC we get more tumour kill.

Right, so you can activate the T-cells, also remove the checkpoint inhibition and then make it all work really well.

Correct, work really well together.

What have you done, though?

We are presenting only the safety this conference and the safety looks very good – very well tolerated drug, we’re not seeing any abnormal safety signals, very similar to what we see with TVEC alone or pembrolizumab alone. We are curious about the rash, the incidence of rash; we’re seeing slightly more rash but again it’s only 21 patients in the safety portion. We had a lead in of TVEC alone for five weeks and then we add in the pembrolizumab so we’re not seeing anything unexpected and we’re seeing a very tolerable regimen. As for the efficacy, we will see that later in the quarter for this year, 2015.

Of course there’s huge interest in this because there have been huge steps forward in melanoma treatment and a nod towards quite efficacious treatment for lung cancers.

Correct, absolutely. I think immunotherapies, particularly the anti-PD1 checkpoint inhibitors, are going to revolutionise cancer treatment.

So what would you say to doctors based on the data you have already and the work that’s ongoing about this combination?

I would watch this space. It is definitely not a combination that we can take into prime time, we still have the phase III study to go. It’s interesting but let’s see the results.

Your study is 1b, does that mean there is any efficacy signal at all?

Yes, in this new era of cancer treatments we’re very much looking for efficacy signals in phase I studies. Now we usen’t fifteen years ago but we’ve become so good at looking at the preclinical work and really selecting out drugs that we think will work, we expect an efficacy signal in most phase I studies.

There’s always a potential for over-treatment whenever you’re combining drugs, but what would you say to summarise about your findings to busy cancer doctors right now about what might be coming up?

A summary, I think the future of treatment is with immunotherapies in cancer. I think we will get some patients with very good long-term benefits on monotherapies. There are still a large number of patients who don’t benefit. We need to combine so that we can aim for that holy grail of cure in cancer. One step first, melanoma, and let’s see if we can do it for other cancers then.