EHA 2024 | Results from a Phase II trial of pirtobrutinib, venetoclax, and obinutuzumab in CLL

So BTK inhibitors plus venetoclax and obinutuzumab are currently being pursued in many different studies in patients with front-line as well as relapsed CLL. In this particular study, we elected to use a non-covalent BTK inhibitor, namely pirtobrutinib, which actually was recently approved in the United States for relapsed/refractory patients with CLL, and combined with venetoclax plus obinutuzumab as a time-limited therapy of one-year duration as first-line therapy for patients with CLL.

So we treated about 40 patients in this study and the median follow-up is just about one year. And what we noted in the study is that we measured the MRD in the blood and the bone marrow by next generation sequencing assay, which has a sensitivity of ten to power minus six. When we did that assay in blood and bone marrow, after about six months of therapy, about 65% of the bone marrow samples and close to 90% of the blood samples were undetectable MRD at 10 to -6, which is a very deep level of remission and similar data when we looked at the one year sample time point was noted as well. In terms of the toxicity, we saw grade 3 or 4 neutropenia of about 60%, which is actually in line with other studies which have reported up to 50-55% neutropenia in this range. But notably there were very few neutropenic fever infections.

So overall, we think this is a very effective regimen which is leading to deep level of remissions for patients with CLL. Currently, we are following these 40 patients, and then we also have an expansion cohort of 40 patients who are enrolling currently and hopefully we will update data at a future medical meeting.