So, my name is Emma Searle. I'm a consultant hematologist at the Christie NHS Foundation Trust in the UK, and I've been very pleased to present the data from the inabrided pomalidomide and dexamethasone study here at ASH 2024. So, this is an all-oral regime for patients who have exhausted standard of care options. In this study, we tested varying doses of the combination of inabrided with pomalidomide and dexamethasone. Most of the patients were very heavily pretreated with a median of five prior lines of therapy. Most of the patients had high markers of disease burden, so they were patients who had very difficult to treat, multiple myeloma. About a third of the patients had had T cell engaging by specific antibodies. And so, what we saw when we used the combination is that we were able, at the highest dosing levels, to achieve response rates of around 75 per cent, so partial response or better, of around 75 per cent. And some of those responses were durable with a median duration of therapy of about six months. I think it's a really exciting time to have a completely different class of drug. So, this has a totally novel target, P300 CBP. So, it's nice to have a different tool in our armoury. Obviously, this is an early development study in Time or Tell, where it finds its place, but it's been great to be able to help patients with treating them with this combination within the study. Inabrided is an oral tablet that targets something called the broma domain of P300 and CBP. So, what we know is that when we target P300 and CBP in that way, that we can influence sort of the chemical factors that we know are key drivers of multiple myeloma, so MIC and IRF4, and that's how this drug works. The other neat thing about this drug is that we had laboratory data before we started the combination studies to guide the combination. So, we knew that at least in the laboratory that cells that had become insensitive to pomalidomide could become sensitive again when we added the trial drug. And then that's what we've seen in the patients as well. So, quite a lot of the patients that we treated with the combination of inabrided, pomalidomide and dexamethasone didn't respond to pomalidomide anymore. In fact, some of the patients were on pomalidomide at the point they were taken into the trial, and we were able to add in the trial drug and see those responses come back. This was very much a dose-finding study and a safety study. So, what we do know is that side effects are clearly really important to patients, and the main side effects that we had with this drug beyond what we'd expect to see with just pomalidomide and dexamethasone alone, just the blood counts, so in particular the platelet count, and we could manage that by the schedule that we gave. So, we gave four days on, three days off, and I think I get concerned about a patient's blood counts, but it doesn't inherently make them feel unwell. So, it's nice to have something that's quite tolerable in a landscape where some of the oral options for patients do have significant side effects. The study's expanding now to, as we're all expected to do these days, to do a larger comparison of a couple of the likely most effective doses, and then beyond that, at some point a pivotable randomised trial would be planned.
HealthTree • December 23, 2024