ASH 2025 | Pivekimab sunirine w/ venetoclax + azacitidine in unfit patients with newly diagnosed AML

Pivekimab sunirine is a CD123 antibody drug conjugate. It uses a chemical payload that causes single-stranded DNA break, which we think may actually result in less damage to normal hematopoietic cells and less myelosuppression. The agent has been extensively evaluated as single-agent. In relapse AML, we published the data in the Lancet Oncology last year. It has about a 25% single agent efficacy, but was also very well tolerated with no capillary leak syndrome, no major severe visceral edema, no VOD in the AML space. It’s also being evaluated in BPDCN. And there, actually, as a single agent, is showing very good efficacy, remission rates, durability, and survival in both salvage and frontline setting, and is hopefully going to get registered there. So based on this, we now developed a frontline study of azacitidine venetoclax, which is the current standard of care for those patients who are older than 75 or not fit for intensive chemo, and are adding the pivacumab to that. And that’s the data we presented from 50 patients treated with this frontline combination. We’re seeing the overall remission rate, the CR rate is very robust, about 85 to 90%. And importantly, the full CR rate, meaning full complete remission, platelet count above 100, ANC above 1, is also very good at about 65%. If you compare this to the CR rates with AZA and venetoclax in the VIA study, this was about 40%. So we think that this is quite a big delta and improvement because of the addition and synergy of the pivacumab. We’re also seeing high MRD negativity rates. And most importantly, when we look at survival, especially in the TP53 wild type, the median survival has not been reached with a median follow-up of about 16 months. And the one-year survival is about 75%, which again is trending favorably to a one-year survival of about 50% we see historically with AZA and venetoclax. So again, I think we’re seeing an improvement in both remission rates, full CR rates, MRD negativity, and overall survival. Now this has to be evaluated in a subsequent randomized study and this is actually something that is being planned and will hopefully happen very soon and of course if that data looks good then this could be a new agent that can be developed in non-mutated specific so mutation agnostic frontline AML.

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