ASCO 2026 | PRIMAVERA trial update: AZD3470, a second-generation PRMT5 inhibitor, in R/R Hodgkin lymphoma

So the PRIMAVERA study is a phase one modular study evaluating the safety and activity of AZD3470 in relapsed/refractory Hodgkin lymphoma. So AZD3470 is a methylthioadenosine cooperative PRMT5 inhibitor, so it’s a second generation PRMT5 inhibitor. And the rationale for targeting PRMT5 in Hodgkin lymphoma is that in Hodgkin lymphoma, you have a loss of methylthioadenosine phosphorylase in about 80% of patients via a unique mechanism of promoter hypermethylation. In solid tumor, the MTAP gene is lost in about 15% of patients by deletion, but in Hodgkin lymphoma is lost in more than 80% of patients by promoter hypermethylation. And why MTAP is relevant for PRMT5? Because if MTAP is not working properly, you have accumulation of this metabolite, methylthioadenosine, which partially inhibits PRMT5 and makes it more sensitive to pharmacologic inhibition. So there is really a great rationale to target PRMT5 in Hodgkin lymphoma for this reason. 

So in this study, we evaluated seven different dose levels in part A, and now part B of dose expansion and optimization is ongoing. Primary endpoints, this is a phase one where those limiting toxicities, like safety, adverse events, and secondary endpoints where response, overall response rate, complete remission rate, progression-free, and overall survival. So far, 68 patients have been treated with AZD3470, and the patient characteristics really reflect pretty much what you can expect from a relapsed/refractory and heavily pretreated Hodgkin lymphoma population. Median age was 45 years. A median number of prior therapies was six, with more than 20% of patients having received at least 10 prior therapies. And all patients had to be exposed to brentuximab vedotin, an anti-PD-1 therapy, before being enrolled in the trial. So this is really a difficult to treat patient population of heavily pretreated patients. 

So safety, regarding safety, the safety profile was really manageable with mainly grade 1, 2 adverse events, no DLTs observed and no treatment discontinuation due to treatment emergent adverse events. And notably, only 3% of patients required dose reduction due to AZD3470-related adverse events. The main adverse event was anemia, observed in 27% of patients, and then nausea, dysgeusia in 15% of patients. And regarding grade 3 or higher adverse events, only anemia was observed in seven percent of patients. So really a manageable safety profile. 

And then regarding responses, data on responses were really interesting because of 59 available patients the overall response rate was 44%. And if we consider only the two highest dose levels, so 450 and 600 milligrams, total 31 patients, overall response was 58% and complete remission rate 35%. The follow-up is still short, so still data is not mature to draw definite conclusion about duration of response and progression-free survival, but at the data cutoff, which was February 2026, the majority of patients treated at the highest dose level were still on treatment and in response. So in conclusion, we can say that AZD3470 displayed evidence of a really manageable toxicity profile and impressive, I would say, clinical activity in really a heavily pretreated patient population. And importantly, this is the first dedicated study of a PRMT5 inhibitor in classic Hodgkin lymphoma. And this is really a paradigm of precision therapy given, you know, the strong rationale of targeting PRMT5 in Hodgkin lymphoma.

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