Data from Enhancer of Zeste Homolog 2 Inhibitor SHR2554 in Relapsed or Refractory Peripheral T-cell Lymphoma: Data from the First-in-Human Phase I Study

• DOI: 10.1158/1078-0432.c.7158192
• Publication Date: 2024-04-01T07:22:05Z
• Authors: Yuqin Song; Zhengming Jin; Zhi-Ming Li; Yanyan Liu; Lanfang Li; Chuan He; Hang Su; Hui Zhou; Kunyan Li; Siguo Hao; Xuelan Zuo; Jianyuan Wu; Dengju Li; Meng Wu; Xiuhua Sun; Junyuan Qi; Zhen Cai; Zengjun Li; Yijing Li; Yanhua Huang; Jie Shen; Zhenyu Xiao; Jun Zhu

<div>AbstractPurpose:<p>Patients with peripheral T-cell lymphomas (PTCL) 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.</p>Patients and Methods:<p>This was a multicenter, two-part, phase I study of SHR2554 in r/r mature lymphoid neoplasms. In part I, 350 mg twice daily was established as the recommended phase II 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 PTCL.</p>Results:<p>Twenty-eight patients were included for analysis (17 angioimmunoblastic T-cell lymphoma and 11 not otherwise specified). Eighteen (64%) patients had received ≥2 lines of previous anticancer therapies. The objective response rate was 61% [95% confidence interval (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.</p>Conclusions:<p>This extended follow-up analysis further supports SHR2554 as a therapeutic opportunity for patients with r/r PTCL.</p></div>