Patients with peripheral T-cell lymphomas (PTCLs) in the relapsed or refractory (r/r) setting have only a limited number of therapies available, and the prognosis is extremely poor. SHR2554 is an oral inhibitor against EZH2, a rational therapeutic target for lymphomas.This was a multicenter, 2-part, phase 1 study of SHR2554 in r/r mature lymphoid neoplasms. In part I, 350 mg twice daily was established as the recommended phase 2 dose (RP2D) based on the findings during dose-escalation and expansion; subsequently, selected lymphoma subtypes were recruited in clinical expansion cohorts to receive SHR2554 at RP2D. Here, we provide an in-depth assessment of SHR2554 at RP2D in subpopulation with r/r PTCLs.Totally, 28 patients were included for analysis (17 angioimmunoblastic T-cell lymphoma and 11 not otherwise specified). 18 (64%) patients had received ≥2 lines of previous anti-cancer therapies. The objective response rate was 61% (95% CI 41-78). Responses were still ongoing in 59% (10/17) of the responders; estimated median duration of response was 12.3 months (95% CI 7.4-not reached). Median progression-free survival was 11.1 months (95% CI 5.3-22.0), and 12-month overall survival rate was 92% (95% CI 72-98). The most common grade 3 or 4 treatment-related adverse events were decreased platelet count (nine [32%]) as well as decreased white blood cell count, decreased neutrophil count, and anemia (four [14%] for each). No treatment-related deaths were reported.This extended follow-up analysis further supports SHR2554 as a therapeutic opportunity for patients with r/r PTCLs.