ICML 2025 | The Phase I/II PRIMAVERA study evaluating AZD3470 in R/R hematological malignancies

So this study actually evaluates the activity and safety, of course, because it’s a phase I/II trial of PRMT5 inhibitors, AZD3470. And the PRMT5 is an enzyme that is involved in methylation of histone and non-histone protein controlling oncogenesis, promoting oncogenesis and controlling gene transcription. More than 80% of Hodgkin lymphoma are deficient in the expression of the MTAP protein which results in partial inhibition of PRMT5, therefore there is a great rationale of targeting PRMT5 in these MTAP deficient tumors through synthetic lethality. 

So this trial evaluates safety and activity of this new oral agent and we’re going to have two parts part 1a which is a dose escalation and part 1b which is going to be dose expansion and the primary focus will be Hodgkin lymphoma. So far the enrollment is ongoing and there are no safety signals and we’re going to see the safety in the upcoming meetings. 

If you’re going to see activity with this agent and the safety profile will be acceptable, then this agent I think there is a great rationale to combine with the other therapies including chemotherapy and immunotherapy as well. So we’re going to see in the upcoming meetings the safety profile and then we will decide from there how to combine this agent best in order to achieve the maximum responses in these patients. Because these are really difficult to treat patients. So the target population is relapsed/refractory Hodgkin lymphoma exposed to all available therapies including brentuximab vedotin and anti-PD-1. So very difficult to treat patient population.

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