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PRIMAVERA — AZD3470 (PRMT5 inhibitor) monotherapy, relapsed/refractory classic Hodgkin lymphoma, ≥3rd line

Abstract: 7003 · Session: Hematologic Malignancies—Lymphoma and CLL, Sat May 30, 2026, 4:00–4:12 PM CT · Presenter: Enrico Derenzini, MD, PhD (Istituto Europeo di Oncologia / University of Milan, Milan, Italy) · Embargo: per ASCO Meeting Library

At a glance

  • Sponsor: AstraZeneca
  • PI / presenter: Enrico Derenzini, MD, PhD (Istituto Europeo di Oncologia / University of Milan)
  • NCT ID: NCT06137144
  • Phase: Phase I/II (modular; this readout = Phase I dose-escalation)
  • Design: Open-label, modular dose-escalation/expansion; ascending once-daily oral AZD3470 monotherapy across dose levels
  • N: 59 evaluable for response (cHL dose-escalation cohort)
  • Primary endpoint(s): Safety/tolerability (DLTs, MTD/RP2D); efficacy by ORR (investigator/IRC)
  • Comparator: None (single-arm monotherapy)
  • Indication: Relapsed/refractory classic Hodgkin lymphoma (R/R cHL)
  • Line: Heavily pretreated — median 6 prior lines (range 3–15); all post-brentuximab vedotin and post-anti–PD-1

Headline result

In the first safety/efficacy readout of the Phase I PRIMAVERA dose-escalation cohort, oral PRMT5 inhibitor AZD3470 monotherapy produced an overall ORR of 44% (26/59 evaluable) in heavily pretreated R/R cHL. Responses were strongly dose-dependent: no responses at ≤100 mg, vs 53% ORR / 27% CR at 450 mg daily (n=15) and 63% ORR / 44% CR at 600 mg daily (n=16); pooled ≥450 mg gave 58% ORR / 35% CR. Pre-meeting trade-press previews highlighted a peak of up to 80% ORR with 50% CR at the optimal dose level among responders. The population was high-risk (median 6 prior lines, 21% with ≥10 prior lines, 68% Ann Arbor stage IV); all had failed brentuximab vedotin and anti–PD-1. No dose-limiting toxicities, treatment-related discontinuations, or treatment-related deaths were reported; any-grade AEs occurred in ~91% (grade ≥3 ~40%), most commonly anemia (27%), fatigue (21%), decreased appetite (15%) and dysgeusia (15%). Median exposure 12.9 weeks; 51% remained on treatment at cutoff. No HR or p-value (single-arm).

Mechanism / class

AZD3470 is a selective, oral protein arginine methyltransferase 5 (PRMT5) inhibitor. PRMT5 is a synthetic-lethal vulnerability when MTAP (methylthioadenosine phosphorylase) is epigenetically silenced — reported in >80% of cHL — making PRMT5 inhibition mechanistically rational in this disease. No PRMT5 inhibitor is approved; AZD3470 is investigational, first-in-human in the PRIMAVERA program.

Discussant takeaway

Framing reported in trade-press preview coverage (Matusar, via CancerNetwork) positioned the data as addressing "a need for patients with relapsed/refractory classic Hodgkin lymphoma who progressed following checkpoint inhibition and brentuximab vedotin" — a setting with few effective options. Formal ASCO discussant remarks not separately reported.

Practice-changing?

Pending. This is early Phase I monotherapy data: encouraging, dose-dependent single-agent activity (CR up to ~44% at 600 mg) with a clean safety profile in a population that has exhausted brentuximab vedotin and PD-1 blockade. It supports advancing AZD3470 (RP2D selection, expansion/combinations) but is not yet practice-changing without larger, confirmatory data and durability/PFS readouts.

  • AACR 2026: ../../aacr-2026/index.md
  • Other ASCO 2026 trials: (no other PRMT5 / cHL trials currently in this vault)

Sources

  • ASCO Meeting Library / J Clin Oncol. 2026;44(suppl 16):7003 — Abstract 7003
  • CancerNetwork — "AZD3470 Displays Clinical Activity in Pretreated Classic Hodgkin Lymphoma": https://www.cancernetwork.com/view/azd3470-displays-clinical-activity-in-pretreated-classic-hodgkin-lymphoma
  • CancerNetwork — "What Are The Top Lymphoma Abstracts at ASCO 2026?": https://www.cancernetwork.com/view/what-are-the-top-lymphoma-abstracts-at-asco-2026-
  • Clinical Trials Arena — "AZD3470 at ASCO 2026: a promising new drug for Hodgkin lymphoma?": https://www.clinicaltrialsarena.com/analyst-comment/azd3470-asco2026-hodgkin-lymphoma/
  • ClinicalTrials.gov — NCT06137144 (PRIMAVERA)