There are about 30,000 cases in the US a year and there are about 750,000 cases of HPV related cancers worldwide a year.

Currently, up until recently, like many other solid tumours there has been no real good treatment for these patients, they tend to receive chemotherapy which makes them live a couple of months longer, sometimes a year or two longer.

More recently in the last year or two or three, there has been the development of checkpoint inhibitors which target proteins either PD1 or PD-L1 which protect the cancer from the immune system.

These drugs have been evaluated for a whole host of solid tumours and they generally, in most solid tumours including HPV associated cancers, including head and neck, anal and cervical cancer, produce responses in about 15-20% of patients.

These are usually durable responses - when patients respond they usually respond for a year or two or maybe even longer.

The drug that we are evaluating, called M7824, blocks this protein PD-L1 but also blocks another protein that the cancer uses to protect itself from the immune system, a cytokine actually.

It’s called TGF-β and there have been large genome-wide association studies comparing thousands of patients with HPV related cancers to patients without cancer.

They’ve looked at the immune pathways, the genes, the proteins, to see what can be something that can be targeted – what’s different in the patients with cancer that’s different from patients without cancer.

They found that this specific protein, or actually this receptor, TGF-β receptor, is significantly over-expressed in these cancers and that this immune pathway is significantly associated with these cancers.

So there’s some logic to trying to see if we can block this pathway as well as block the PD-L1 pathway which has had some success in these cancers.

So we conducted a phase I trial of a drug called M7824 which blocks both of these pathways.

We conducted it in all solid tumours and we enrolled initially 36 patients but at this point the drug has been tested in over 500 patients.

So we just looked at the patients with HPV related cancers and the 36 patients that we enrolled.

We were just trying to get an early feel for how effective it was compared to just PD-L1 inhibition alone.

So we saw that about 35% of patients, not respective of their HPV status, just including head and neck, anal and cervical cancers, responded to this treatment.

Of the patients who had HPV positivity or we could detect that their cancers were due to HPV, we saw 42% response rate and all of these patients continued to respond. And I’m happy to answer any questions about that.

Were there any dose limiting toxicities or any maximum dose levels?

Yes.

So, we evaluated five dose levels.

At dose level 4 there was one DLT of colitis.

As a standard phase I trial we will only call a maximum tolerated dose if we have 2 DLTs out of 6 and we did not have 2 DLTs at any dose level nor do we have any other DLTs at any other dose level.

So, no, there was no maximum tolerated dose and the standard dose that’s going to be used for the recommended phase II dose is going to be 1200mg flat dose.

That’s based upon pharmacokinetic and pharmacodynamics modelling that has been done.

So trial ongoing or are there plans to escalate into a phase II based on the response rate?

There’s now actually an ongoing phase II trial specifically for M7824 in HPV associated cancers.

There are also ongoing phase Ib expansion cohorts in other disease tumour types as well.