ICML 2021 | Duvelisib plus romidepsin in r/r PTCL

We presented final results of combination romidepsin and duvelisib. So this started as a phase one study looking at the safe dose or the tolerated doses for the combination, and in that, we saw particularly high responses in peripheral T-cell lymphomas with lower responses in cutaneous T-cell lymphoma. So we undertook an expansion, a phase two expansion, specifically in peripheral T-cell lymphoma to see if we could statistically show that the combination was better than the single agent activity for romidepsin alone. And we benchmarked our combination goal activity at 50%. So in that expansion, which was over 50 patients in total for the study, we had a response rate of over 50% with a high rate of complete responses. So we feel that that combination is active and more active than a single agent romidepsin.

And then I think when we got into the subtypes, as we’ve seen in other studies, there was particularly high responses and high complete responses in patients with angioimmunoblastic or follicular helper T-cell lymphomas, and there’s been other studies where that subtype seems to be more responsive, particularly to drugs that are epigenetic modifiers, so that maybe fits thematically. So in that sense, those were the main end points of the study.

I think the other interesting things that we found was that a good portion of patients responded completely and then bridged to allotransplant. And we showed the data that using this as a lead into allotransplant, at least we didn’t see any obvious safety signal. There was not a significant increase in early GVH or toxicity of the transplant. So we think this regimen, when it creates a complete or near complete response, could be safely used as a bridge to transplant with curative intent. And then the other thing that I think is interesting about this is when we gave romidepsin with duvelisib, we were able to give full dose duvelisib.

So duvelisib had 75 milligrams twice daily, which is much higher than the approved dose for low grade B-cell lymphomas. And in the phase one study of duvelisib where we established the maximum tolerated dose to 75 twice daily, the rate of transaminase elevation, which is one of the more common side effects was about 40%. And when we give it in combination with romidepsin, now in over 50 patients, we see a grade three to four transaminase elevations, sorry to clarify, of only about 10%. So our thought is that the romidepsin may be somehow protective against some of those inflammatory side effects. So potentially it adds efficacy, potentially it increases safety, potentially it allows more exposure to duvelisib, which we think is an active agent.

So all of that was in the analysis of the study and I think the next steps, again, as people may know, there’s a large registration study of single-agent duvelisib in relapsed or refractory T-cell lymphoma, and I think once we have that data, we may be able to compare and try to better assess what romidepsin may be adding in terms of efficacy and or toxicity.