Can you tell me about the ProMMise trial which opened up a few weeks ago?

Four or five years ago I was on the first in human trials of belantamab mafodotin and we saw some very good results. It was fairly clear from that stage that this was going to be a treatment that was going to be a useful treatment for myeloma. Given that it was showing some good effects in patients who had no real other treatments, we wanted to develop a trial for patients who are much earlier on in the treatment pathway.

What is unique about this study?

There are two aspects we wanted to focus on, the first was looking at combinations of treatments which were more low cost because belantamab is very expensive. With these drugs once you start combining them, they just become impossible for healthcare systems across the globe. The second component relates to the effect on visual function which means patients have to see an ophthalmologist before every treatment so we wanted to try and explore other ways of assessing their eyes.

It is a flexible adaptive trial with multiple arms which allows us to explore a low-cost combination- cyclophosphamide and dexamethasone – and then on top of that builds in the ophthalmology part. That is quite a novel design because we’re using patient reported outcome measures to help guide us and we’re the only trial that is going to do this in a randomised way.

What do we know about belantamab already?

It’s licenced both in the US in Europe for patients who’ve had at least four previous myeloma treatments on the basis of the pivotal DREAMM-2 trial that demonstrated response rates of about 30%. Those patients who are responding they can do quite well and the latest data shows there is good survival as well. A number of other trials are exploring its indication earlier on in the treatment pathway and in combinations.

How many patients are you recruiting?

At the moment we have four arms, although it’s a live dynamic trial and we’re going to be closing and opening arms as we go and that’s one of the key advantages of this trial which means you can try and keep it up to date and future proof. We’re looking at about 30 to 35 patients per arm but of course that can change. There are two sites open at the moment at UCLH and in Wales and we will also have Nottingham Southampton, Leeds and the Royal Marsden in London.

What are the outcomes you are looking at?
The primary endpoint is about the safety and tolerability and of the combinations. So firstly, the cyclophosphamide, dexamethasone and belantamab, a three-drug combination and then we will have a four-drug combination where we add ixazomib.

Then we have secondary endpoints of efficacy and we will be looking at subgroups. A new key new endpoint that we’re adding is that to collect data on ethnicity and social deprivation. It’s important to look at underserved populations to ensure that we’re enrolling these groups. There’s also whole translational element, still in development, where patients are donating blood and bone marrow biopsies, so we can look for biomarkers of response and resistance.

Can you see this type of adaptive trial, testing multiple treatments at once, becoming more commonplace?

Yes absolutely, I already have a second trial in setup through Myeloma UK’s Concept and Access Research Programme which is a similar sort of approach. I think this is the way to do it, because it’s a much more efficient way of running studies and it also allows you to future proof it. In ProMMise, we are dropping the monotherapy arm because since we conceived the trial and it opening, which was delayed because of COVID, there’s been a lot of data on belantamab monotherapy and we don’t need to duplicate that.

What we’re seeing now in cancer across the board is that drugs are moving incredibly rapidly. You run the danger of setting up a trial which is out of date by the time it’s reported and that’s a major problem across the board.

What have been the main challenges to getting this set up?

One of the things we’ve discovered is when you’re setting up the protocols, you have to be very careful about how do you deal with multiple protocols and multiple patient information sheets, because as soon as one small thing happens on one arm, you then have to amend everything accordingly, and that takes a lot of effort and time. In the second platform study I’m developing, we’re now trying to speed that up and make it more efficient.

The second challenge has been working with two different pharmaceutical companies because of the requirements on their contracting and the legal side. That’s unfortunately slowed down the third arm of this trial.

What’s your Holy Grail — the one thing you’d like to achieve in your research career? 

I would like to be part of a research project that leads to the cure of myeloma. This will involve lots of people globally, but given the pace of advances this may well be achievable during my career.

What aspect of your research excites you the most?
Being able to design and deliver highly innovative trials that leads to rapid translation of benefit to patients

The trial was developed under the Concept and Access Research Programme (CARP) initiative and funded by the charity Myeloma UK.