AZD3470 Displays Clinical Activity in Pretreated Classic Hodgkin Lymphoma

Giving the PRMT5 inhibitor AZD3470 as monotherapy showed clinical activity among patients with classic Hodgkin lymphoma who relapsed or were refractory to brentuximab vedotin (Adcetris) and an anti–PD-1 therapy, according to findings from the phase 1 PRIMAVERA trial (NCT06137144) presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.

What Were the Key Efficacy Data?

Specifically, among 59 evaluable patients who received AZD3470, 26 (44%) experienced an objective response. The objective response rate (ORR) and complete remission (CR) rate with AZD3470 were highest at doses of 450 mg or higher: 58% and 35%, respectively. In the 450-mg daily cohort (n = 15), the ORR was 53%, and the CR rate was 27%. In the 600-mg daily cohort (n = 16), the rates were 63% and 44%, respectively.

Notably, there were no responders among 12 patients treated with 100 mg or less of treatment.

The most common discontinuation factor was disease progression. Dose expansion and optimization is ongoing. Furthermore, the majority of patients treated with higher doses of AZD3470 experienced a response and were receiving ongoing treatment as of the data cutoff date.

“AZD3470 shows clinical activity in patients with classic Hodgkin lymphoma previously treated with brentuximab vedotin and anti–PD-1 therapy,” Enrico Derenzini, MD, director of the Oncohematology Division at Instituto Europeo Di Oncologia and an associate professor of Hematology at the University of Milan, stated in his presentation of the PRIMAVERA findings. “The [ORR] and CR rate were highest in doses higher or equal to 450 mg daily, the [ORR] was 58%, and the [CR] rate was 35%. Data for duration of response and progression-free survival [PFS] are pending due to the short follow-up.”

PRIMAVERA Design and Population

The phase 1/2 dose escalation and expansion protocol evaluated oral AZD3470 among the relapsed/refractory classic Hodgkin lymphoma population. Patients 18 years and older were required to have a histological confirmation of relapsed/refractory disease; an ECOG performance status of 0 to 1; and at least 3 prior lines of therapy for classic Hodgkin lymphoma, including brentuximab vedotin and an anti–PD-1 therapy, to have been eligible for enrollment on the study.

The median age on the study was 45.5 years (range, 22-78), with most patients being male (66%) and White (60%). A total of 46% vs 44% of patients had relapsed or refractory status, 68% had Ann Arbor Stage IV disease, and 90% did not have bulky disease. The median number of prior therapies was 6.0 (range, 3-15), with 21% of patients having received 10 or more lines of prior therapy. The most common anticancer therapies included an anti–PD-1 agent (91%), brentuximab vedotin (90%), radiotherapy (47%), and autologous stem cell transplantation.

The primary end points of the phase 1 portion of the study included safety and tolerability of AZD3470, dose-limiting toxicities (DLTs), and recommended phase 2 dose. Secondary end points included ORR, CR rate, PFS, and overall survival.

Safety Outcomes

The median duration of exposure to AZD3470 was 12.9 weeks (range, 2.7-61.1), with 51% of patients remaining on therapy at data cut off. No DLTs, TEAE-related discontinuations, or deaths were observed among patients treated with AZD3470.

Any treatment-emergent adverse effects (TEAEs) occurred in 91% of patients, including 69% who experienced TEAEs possibly related to AZD3470. Grade 3 or higher TEAEs occurred in 40%, of which 21% were possibly attributable to the agent. TEAE-related dose reductions occurred in 3% of patients, and serious AEs were noted in 19%.

The most common treatment-related AEs (TRAEs) included anemia (27%), fatigue (21%), decreased appetite (15%), and dysgeusia (15%). Additionally, anemia (7%) was the most common grade 3 or higher TRAE.

Disclosure: Derenzini noted receiving honoraria from AbbVie, AstraZeneca, Incyte, and Roche; disclosed consulting or advisory roles with, AbbVie, AstraZeneca, BeiGene, Roche, and Takeda; noted being on the Speaker’s Bureau for AbbVie, AstraZeneca, Incyte, and Roche; received research funding from ADC Therapeutics, Incyte, Takeda, and TG Therapeutics; and received compensation for travel expenses from AbbVie and AstraZeneca.

Reference

Derenzini E, Morschhauser F, Ribrag V, et al. A phase 1 study of the PRMT5 inhibitor AZD3470 in patients with relapsed/refractory classic Hodgkin lymphoma (PRIMAVERA). J Clin Oncol. 2026;44(suppl 16):7003. doi:10.1200/JCO.2026.44.16_suppl.7003