This data was phase II data of copanlisib, which is the Bayer class 1 PI3 kinase inhibitor, preferential activity inhibiting the alpha and delta isoforms. This trial was developed on the back of the phase I data which was showing interesting activity, particularly in non-Hodgkin’s lymphoma. So the data we presented was the phase II; we had recruitment from both indolent and aggressive lymphoma patients in the relapsed refractory setting. So these patients were really quite tough, they’d had at least two lines of prior therapy, even up to ten prior lines, and were spread across the age ranges. It’s hard to imagine but the oldest patient in the trial was 90, so this was truly representative of how difficult it can be with patients in the relapsed refractory setting.

The drug was quite well tolerated, it’s given IV on the schedule so intravenously on day 1, 8 and 15, so that’s three doses every four weeks. There are toxicities but generally fairly well managed. It’s interesting, probably because of an effect with PI3 kinase alpha inhibition, that the insulin homeostasis is disturbed so patients can quite commonly get a rise in their glucose levels on the day of an infusion but this doesn’t usually turn out to be something too troublesome and it’s easily managed. There have been other readouts – hypertension that has sometimes required treatment in some patients but again not too bad, and a small signal with pneumonia and pneumonitis which is something that just has to be kept an eye on.

In terms of response rates the data was quite impressive, particularly for indolent lymphomas with, across the board, a different pathology showing a good response rate. Actually three complete remissions were seen in the follicular lymphoma cohort that was evaluable. So that’s certainly encouraging to take forward.

As things stand the data is looking good, it’s all hypothesis generating and pushing forward to the next trials. Bayer are currently extending recruitment for the phase II component in the indolent lymphoma so we’re busily recruiting, and Cambridge are recruiting, as well as other centres across the UK and internationally. Then the company have a plan to extend the programme with this drug to include randomised trials with and without rituximab and, as you’d expect, taking the drug forward in different directions, including actually in the aggressive lymphomas.

What’s next?

Of course next in the world of indolent lymphoma will be we’re moving into an age of combination therapies, really, where these drugs, things like this as a PI3 kinase inhibitor but other inhibitors of different aspects of signalling pathways, they’re all going to be combined with different antibodies, potentially different chemotherapies as well, really to push those remissions deeper to give our patients better, more durable remissions going forward.

What kind of response did you receive?

I think it is positive. Of course the space is quite crowded because there are drugs there already, there’s idelalisib which has already got licence approval for relapsed refractory indolent lymphoma. There are other PI3 kinase inhibitors as well – there’s the drug from Infinity, TG Therapeutics have got one in development, Amgen have got drugs in development, so it is quite a crowded space. That’s triggering a lot of the debate, where will these individual compounds sit. But, as I always say, it’s better to have a cupboard full of choices that you can bring together because each drug is looking a bit different, they’ve got different side effect profiles, probably have different specific activity with disease groups. So going forward the space is crowded, which is great, but clever trial design and let’s get these drugs through to our patients.

Is there a message you would like to end on?

My message is, everyone who is listening, the world is changing for lymphoma and CLL. It’s a tremendously exciting time for clinicians and those of us running clinical trials. Of course, we’re all hoping so much that our patients who are going forward, we’re doing everything here for our patients, that their outlook in the near future is going to be better than historically it has been.