ASH 2025 | Interim analysis of a Phase II study of the GLOVe regimen in untreated, high-risk MCL

The GLOVe Regimen is a study that we designed. We formally did a frontline study with a regimen using lenalidomide and venetoclax. Unfortunately with that regimen what we were able to see is that patients who had p53 mutations unfortunately didn’t have durable responses. So because that was right around the time we would start using the bispecific antibodies. The Genentech 179 study was open at our site. We started enrolling patients to glofitamab. We did see some responses in these patients who had progressed on the Valor study. And glofitamab, lenalidomide, and venetoclax in patients with untreated high-risk mantle cell lymphoma. So there’s not a true definition of high-risk mantle cell lymphoma that people can agree upon, but so we did extract sort of what the baseline demographics of high-risk was from Jane et al from JCO. What we identified specifically P53 mutations, patients with elevated Ki-67, generally 50% or higher, blast over pleomorphic variant, complex cytogenetics, and a high MIPI score, generally using the MIPI-C, with recent data showing that that distinguishes itself from the other sort of great stages of MIPI. So with this regimen, we started off with a lead-in regimen of venetoclax, ramped that up to 200 milligrams, and then added obinutuzumab. And then at that point, we introduced glofitamab and the standard step-up dosing 2.5, 10, then 30 milligrams. Thereafter, we did introduce lenalidomide. So from this preliminary evaluation, as the study is planned to enroll 50 patients. At this ASH meeting, we will present data. And the data we presented is with the first 27 evaluable patients. So what we’ve seen in this situation is that thankfully we’ve had responses in all the patients we’ve treated on study. We do have a few responses in the evaluable patients due to unfortunate issues that led up during the ramp up of the venetoclax. So these patients were not response evaluable. But all the patients who’ve been able to get a response, we’ve been able to attain an overall response rate. The vast majority of these patients have had a complete response. And also the vast majority of these patients have been able to obtain an undetectable MRD result with the Clono-seq assay. We’ve only had one person at the first response assessment, which is at nine weeks, which had a MRD assay that was still detectable above 10 to the negative six. So far of the patients, we’ve not had any relapses of the mantle cell lymphoma, although follow-up is short. We have a median follow-up of about 10 months. And ideally, with this patient population, we’ll need much more follow-up to determine the duration of response. But thus far, we’ve had appropriate safety, as we’ve noticed some appropriate reduction in cytokine release syndrome. So the data set that we have shows that our CRS rates are lower than what we even saw in the relapsed/refractory setting, which is encouraging given the higher disease bulk and fitter T-cell population in our patients compared to what we see in the relapsed/refractory setting. As we move forward, the goal is to continue to complete the remaining, which will be around 22 patients. We do have several subsites that are open and enrolled in patients. So we hope to come back to an ASH in the future with more mature data set. And hopefully, this will support more evidence of introducing bispecifics in frontline mantle cell lymphoma.

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