ASH 2024 | Phase II study of acalabrutinib, venetoclax, and obinutuzumab in CLL enriched for high-risk disease

So at this year’s ASH meeting, I’m presenting the primary results of our study of AVO, acalabrutinib, venetoclax, and obinutuzumab, in a population of CLL patients in the frontline setting that’s enriched for those with high-risk disease with TP53 aberration. Also at this ASH meeting, we’re going to see the AMPLIFY results for the first time. This is a big Phase III trial looking in the non-TP53 aberrant, so lower risk population, with the AVO triplet, AV is a doublet, and chemoimmunotherapy. So our study really complements that larger Phase III data set because it’s looking at that population that was excluded from AMPLIFY. 

We have 72 patients in our multi-center Phase II study. We’ve used a regimen where we introduce acalabrutinib first, then we layer in obinutuzumab for a couple months, and then we do the triplet therapy for four cycles, and then patients get additional AV doublet therapy. Our study uses an MRD-guided strategy for therapy duration, so patients can get basically about a little over a year of therapy or two years of therapy based on whether they achieve undetectable MRD and complete remission at the cycle 16 day one time point. So that’s the primary endpoint of the study is CR with undetectable MRD at cycle 16. And this was achieved by 42% of the patients on the study, both in the high-risk patients and in the overall cohort. So no decrement there in the high-risk patients. When we look just at bone marrow MRD at that time point in cycle 16, 71% of the patients with the high-risk disease achieved that milestone, 78% of the overall population. 

Really importantly in the front-line setting is PFS. We actually have fairly mature follow-up for this study. Median is a 55-month follow-up. And at that time frame, the PFS for the high-risk patients is about 70%. And for those with overall in the non-TP53 population, it’s 96%. So these numbers do compare favorably to what we would expect from venetoclax obinutuzumab on its own, for example. We do have a little bit longer therapy duration, so that might account for some of the PFS advantages. But we also think there may be some synergy of combining these different mechanisms, particularly for the high-risk patients. So I’m happy to say that our study is being presented here at ASH, but we’re also simultaneously publishing the results in Journal of Clinical Oncology, so we hope you’ll check out our article.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.