Tandem Meetings 2023 | Safety & efficacy of LV20.19 CAR-T therapy in Richter’s transformation and R/R MCL

We have sort of two different presentations. We have a poster presentation initially looking at outcomes for Richter’s transformation. As people know, Richter’s transformation is a rare sort of complication of CLL, but when it occurs it has a really poor prognosis. And so these patients often can go through multiple lines of therapy very quickly and progress with disease.

And so we sort of looked at our experience treating Richter’s across multiple clinical trials using the LV20.19 CAR-T product and sort of identified 6 patients in total. 2 from the original study, 4 on the current study… And basically found really nice outcomes. We had an overall response rate of 100% percent and we’ve had two relapses in the 6 patients, but the others actually achieved a meaningful and durable remission. One interesting thing that we found is that these Richter’s patients had a little bit different toxicity profile with almost all of them having an HLH-like toxicity with hyperferritinemia, LFT abnormalities, coagulopathy. And so something I think we need to learn more about, this is a different disease. I don’t think there’s a lot of data out there about CAR T-cells and Richter’s sort of limited to some case series and case reports, but we demonstrated that CAR T-cells specific, this bispecific CAR is very effective. Although the types of three profile was a little bit unique but very manageable.

And then in terms of mantle cell lymphoma, we are presenting the interim results of the Phase I/II study as an oral presentation tomorrow in mantle cell lymphoma. And for this, this was a Phase II study that was sort of based on improving the CR rate compared to BTK inhibitors, which is sort of the standard second-line therapy or third-line therapy for mantle cell lymphoma. And we now have enough data to report on 14 patients, 3 that were treated during the Phase I, 11 during the Phase II, these were heavily pretreated mantle cell patients, many of whom had multiple lines of therapy and including auto autologous transplant, allogeneic transplant with a median of 5 prior lines. And so from a safety standpoint, again, we saw really, really good safety signal, no grade 3 to 4 CRS, 2 patients that had great 3 to 4 ICANS. Interestingly, 1 of them had concurrent mantle cell in the CSF that we found at the time of the ICANS developing. And then in terms of overall response rate at day 28, the overall response rate was 100% and our primary outcome, which was day 90, overall response rate, we had a CR rate of 92%, partial response of 8%, and again, an overall response rate of 100%. And we met our sort of primary endpoint with 8 or more patients achieving a day 90 CR to date, which is why we’re going to be pushing this forward and hoping to launch a multi-center trial like we did with zamtocabtagene specifically for mantle cell lymphoma.