AZD3470 (MTA-cooperative PRMT5 inhibitor) hits 80% ORR/50% CR in MTAP-deficient r/r cHL (Phase 1)

AZD3470 is an oral, MTA-cooperative PRMT5 inhibitor designed to preferentially engage PRMT5 in MTAP-deficient tumor cells; in this first-in-human Phase 1 PRIMAVERA dose-escalation study (NCT06137144), adults with relapsed/refractory classic Hodgkin lymphoma after ≥3 prior lines including brentuximab vedotin and anti–PD-1 received once-daily monotherapy across dose levels DL1–DL8 (39 treated; 31 efficacy-evaluable). As of the Nov 25, 2025 cutoff, patients were heavily pretreated (median 6 prior lines; 51% prior auto-HSCT; 13% allo-HSCT) and all evaluable tumors were MTAP-deficient; among efficacy-evaluable patients, 14/31 responded, with responses emerging at ≥DL4 and the highest activity at ≥DL7 (n=10) showing ORR 80% and CRR 50%—numerically in the same ballpark as camidanlumab tesirine’s Phase 2 post–BV/PD-1 dataset (ORR 86.5%, CR 48.6%). Safety looked manageable: TEAEs in 85% were mostly Grade 1–2 (anemia 28%, nausea 15%); Grade ≥3 TEAEs occurred in 28% (notably neutropenia and hypokalemia, n=2 each), with 13% serious TEAEs, only 2 dose reductions, and no DLTs, TEAE-related discontinuations, or TEAE-related deaths—though follow-up/exposure remains relatively short (median 15 weeks) and durability metrics (DoR/PFS) were not reported.