ICML 2025 | Phase II study of subcutaneous mosunetuzumab + polatuzumab vedotin in post-BTK inhibitor R/R MCL

Yeah, so this is a very exciting Phase II study using the regimen containing mosunetuzumab and polatuzumab. You know, both targeting B-cells but with different mechanisms of action. The mosunetuzumab is a bispecific antibody recruiting T-cells and polatuzumab is an antibody drug conjugate targeting CD79b and delivering a payload, so killing the target cells via different mechanisms. So when we combine these two, this is a primary analysis of the full cohort with 42 patients enrolled into the study. Among these 42 patients, these are all newly diagnosed mantle cell lymphoma patients. They have at least two prior lines of therapy. They all need to have a prior anti-CD20 antibody, need to have either anthracycline or bendamustine-containing regimen, and also they all need to be, have had exposure to BTK inhibitors. So 100% of them have prior BTK inhibitor treatment. And in these 42 patients that were treated under this Phase II cohort, we see a pretty difficult-to-treat patient population. 71% of them have three and higher risk factors and this includes a high MIPI score, MIPI score of 6 and higher, including patients, you know, patients who have extranodal or bone marrow involvement, including patients with elevated LDH. And we also see almost, you know, 30% of patients already have prior T-cell treatment, and also a similar percent of patients have prior autologous stem cell transplant. So despite these, you know, high-risk features of the treated patients, we see extremely high efficacy with a CR rate of 79% and overall response rate 87%. So in this heavily pretreated patient population, and when we break down the patients into elderly age, elevated LDH, TP53 mutation or deletion, high MIPI score, across all these high-risk groups, the high efficacy really persists throughout all these groups. So the results are quite satisfactory. When we look at the safety profile, the mosun-pola actually had a CRS rate of 44%, which is actually quite, compared to other regimens using bispecifics, this is actually quite favorable. And all these CRS rates are low grade, grade 1 and grade 2. And some patients had neutropenia, but febrile neutropenia was only seen in five patients, so 2% and so therefore we think this is a regimen that is highly efficacious and also quite safe to give in the outpatient setting. There’s no required hospitalization requirement. It’s also given in a fixed duration fashion, a total of 17 cycles. Now polatuzumab is given on the first six cycles, mosunetuzumab is given for a total of 17 cycles and that’s it. So it’s fixed duration and we see very nice B-cell recovery once the patient completed treatment. So by nine to 12 months post-treatment, almost the majority of the patients already had B-cell recovery to normal range. So this is a regimen we’re very excited. We hope to bring this regimen to be tested in a broader mantle cell lymphoma patient population and also at earlier lines of treatment.

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