ASH 2024 | A Phase Ib study of venetoclax plus 7+3 induction chemotherapy in newly diagnosed AML

So it was an early phase, Phase Ib study of venetoclax in combination with 7+3. It was a dose escalation in terms of venetoclax cumulative dose, so duration essentially of venetoclax at eight, 11, 14 days in combination with 7+3. And then subsequently in consolidation for responding patients, venetoclax in combination with intermediate-dose cytarabine, sort of following this most widely used standard of care approach for fit patients with acute myeloid leukemia. So we looked, because it’s a relatively novel combination, that was, the primary point was safety evaluation. So we did that in a dose escalation fashion, and we progressed to the duration of venetoclax based on how the prior cohort of patients tolerated the combination. And a secondary endpoint was obviously efficacy endpoints. And we particularly looked at MRD negative CR rate because that’s kind of a marker and potentially surrogate marker for survival endpoints down the road. We found in terms of safety that the addition of venetoclax to 7+3 chemotherapy, whether that was eight, 11 or 14 days, did not quite change the toxicity profile of 7+3 alone, which was quite a relief. Obviously the concern was additive myelosuppression to a 7+3 regimen, and we did not thankfully see that at any of the tested durations of venetoclax. And then when we looked at efficacy endpoints, survival endpoints are very difficult to make a comment right now, the follow up is short. But in terms of the quality of response, the depth of the response, the MRD negative CR rate, we found a pretty high CR rate across the venetoclax duration cohorts. And if we combine them all together, we had a composite CR rate of 85%, and 86% of those patients were MRD negative by flow cytometry that was also evaluated centrally in a reliable reference lab with a very good sensitivity. I think that these are the key points and to make a couple of additional points, you know, frequently in the induction therapy of acute myeloid leukemia, patients require double induction to achieve that first milestone of CR. All of our responses were achieved with one induction, so that’s a positive finding as well in a way, we mitigating the need for double induction that can add toxicity to the initial phase of therapy.

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