ASCO 2016

Preliminary results from KEYNOTE-055: pembrolizumab in HNSCC

Dr Joshua Bauml - University of Pennsylvania, Philadelphia, USA

This year I have the pleasure of presenting the preliminary results from KEYNOTE-055. This is a study of pembrolizumab, the PD-1 antibody, for treatment of recurrent or metastatic head and neck cancer that is refractory or resistant to both platinum and cetuximab.

What has been the process of patient selection going forwards after they’ve already failed with the platinum and cetuximab?

In the modern era there’s actually no active therapies for patients who fail both platinum and cetuximab. The usual historical reference population is methotrexate. Methotrexate has a response rate of about 5% and patients have a median overall survival of 6 months. So this is a patient population with significant needs and there’s reason to think that pembrolizumab would be active here because both PD-L1 and PD-L2 are up-regulated in head and neck cancer.

It’s not often we hear about PD-L2.

Right, so it’s another ligand for PD-1.

It’s part of the whole KEYNOTE overview of trials, how is this feeding into information?

It’s a very exciting trial because this is a space, as I said, where there are no real options. There’s actually never been a trial, to my knowledge, in this spot; most trials will say you can’t have received cetuximab or whatever, but this is really taking the sickest of the sick and we saw some really exciting results.

Will you tell us more about those?

Yes, so we presented the 92 patients with at least 6 months of follow up and there was around a 17% response rate that was all partial responses. But keep in mind PD-1 agents can have responses that happen after 6 months so it is fully possible, we’ll have to watch more and see where we are. We also, in addition to that, saw about 17-18% of stable disease. So there was a large amount of clinical benefit for these patients.

With the ongoing patient surveillance in mind for this cohort, are there any plans to expand beyond the original 98 patients?

We have actually enrolled 172 patients and 171 have been treated. At ASCO this year we’re just presenting the first 92 who have at least 6 months of follow up because we’re only presenting confirmed responses here. So the investigator assessed response rate may actually be higher but we’re presenting confirmed response using the most rigorous fashion with independent radiologic review.

Just to check, for the proportion of patients who have, say, head and neck cancer going through the treatment cycle, getting a platinum, getting all the treatment so far, how many of those patients would be eligible for further trials with KEYNOTE-055?

If a patient has recurrent or metastatic disease they will likely go on to need further treatments because it’s unfortunately incurable. So if they’re starting with platinum, if they had platinum which they were resistant to in the locally advanced setting then we can’t give them that again. We have cetuximab and then we really have very limited options there. So there’s a big population who stand to benefit from these results.

With that big population in mind, how would you see this being escalated out from the enrolment so far up to the next few phases of trials?

There are ongoing phase III trials that are comparing pembrolizumab against or in combination with cytotoxic chemotherapy. Those are KEYNOTE-040 and KEYNOTE-048 and those are ongoing and currently accruing.

Checkpoint combinations seem to be very much the treatment du jour, the idea of being able to kill and limit cancer growth. How do you see that moving forwards as a broader application in the field?

I think that within head and neck cancer at least it’s a great opportunity because many patients with head and neck cancer, for instance, have a virally mediated cancer, for instance human papilloma virus or Epstein-Barr virus. So the concept of combining a checkpoint inhibitor with perhaps a therapy targeting a viral antigen, that’s a really exciting next step. And also doing this in a logical scientific fashion, saying we know that these are the markers that are found in head and neck cancer and structuring a trial around that, combining what we know with what we wish to know.