SHR2554 in patients with R/R PTCL: Results from a phase I trial

In patients with peripheral T-cell lymphoma (PTCL), inhibiting enhancer of zeste homolog 2 (EZH2), a key histone methyltransferase, is a rational treatment approach.¹ SHR2554 is an oral, small-molecule, selective EZH2 inhibitor.¹ A multicenter, two-part, phase I trial (NCT03603951) investigated the safety and efficacy of SHR2554 in patients with relapsed/refractory (R/R) lymphoma.¹ In part 1, the recommended dose of SHR2554 350 mg twice daily demonstrated antitumor activity across several lymphoma types, including R/R PTCL.¹ Part 2 assessed the safety and efficacy of SHR2554 in 67 patients aged 18–70 years with R/R PTCL following prior chemotherapy and ≥1 novel agent approved in China.¹

During the European Hematology Association (EHA) 2025 Congress, June 12–15, 2025, Milan, IT, Yuqin Song presented results from Part 2 of this trial. The primary endpoint was the overall response rate (ORR).¹ Key secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. The median follow-up was 15.2 months.¹

Key learnings

The primary endpoint was met: the ORR was 64.2%, with a CR rate of 32.8%. The ORR benefit was observed across PTCL subtypes (AITL, 70.3%; PTCL-NOS, 57.1%; ENKTL-NT, 50.0%; ALCL, ALK−, 42.9%; ALCL, ALK+, 50.0%; MEITL, 100%).

The median DoR, PFS, and OS were 18.7 months, 10.0 months, and not reached, respectively. 

Any-grade TEAEs and Grade ≥3 TEAEs occurred in 92.5% and 61.2% of patients, respectively. The most common Grade ≥3 TEAEs were decreased platelet count (28.4%), decreased neutrophil count (26.9%), decreased WBC count (25.4%), and anemia (23.9%).

SHR2554 demonstrated efficacy and a manageable safety profile across PTCL subtypes, making it a potentially new therapeutic option for this challenging-to-treat population. A phase III study comparing SHR2554 vs tucidinostat for R/R PTCL is currently ongoing (NCT06122389).