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Background <p>Peripheral T-cell lymphoma (PTCL) is an aggressive malignancy with limited treatment options and poor prognosis, particularly for relapsed or refractory (r/r) patients. HH2853, a novel dual inhibitor of EZH1/2, has previously demonstrated clinical benefits in solid tumors. Here, we report safety and efficacy data from a phase Ib trial of HH2853 in r/r PTCL.</p> Methods <p>A phase Ib clinical trial in PTCL was conducted from July 2022–August 2023 at 15 sites in China. The study employed a dose-escalation phase (300&#xa0;mg, 400&#xa0;mg, and 600&#xa0;mg BID) to determine the recommended phase II dosage (RP2D), followed by a dose expansion phase (300&#xa0;mg and 400&#xa0;mg BID). The primary endpoints were safety and the overall response rate (ORR).</p> Results <p>Thirty-four patients with various r/r PTCL histology types, a median age of 58 years, and a median of 2 prior systemic therapies were enrolled. Treatment-related adverse events (TRAEs) were observed in 92.1% of the patients, with 20.6% experiencing grade 3 TRAEs. The most common TRAEs included anemia (67.6%), thrombocytopenia (52.9%), leukopenia (44.1%), and diarrhea (38.2%). One patient (2.9%) receiving 600&#xa0;mg BID experienced dose-limiting toxicity due to grade 4 thrombocytopenia. The dose of 400&#xa0;mg BID was selected as the RP2D. The ORR was 67.6%, comprising 29.4% complete remission and 38.2% partial remission. As of the data cutoff in September 2024, the median follow-up period was 15.7 months, with a median duration of response of 14.8 months; overall survival had not yet been reached.</p> Conclusions <p>The selective EZH1/2 dual inhibitor HH2853 demonstrated acceptable and manageable safety profiles and promising efficacy in r/r PTCL patients, indicating its therapeutic potential for this difficult-to-treat patient population.</p> Trial registration <p>NCT04390737</p>

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A multicenter, open-label, single-arm, phase Ib clinical trial of HH2853 treatment in patients with relapsed and/or refractory peripheral T-cell lymphoma

  • 期刊论文

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  • 发表日期：

    2025年4月27日

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  • Huangming Hong,
  • Zegeng Chen,
  • Mingzhi Zhang,
  • Zhigang Peng,
  • Jianzhen Shen,
  • Yuerong Shuang,
  • Hui Zhou,
  • Hongqiang Guo,
  • He Huang,
  • Fei Li,
  • Zhengzi Qian,
  • Lihong Liu,
  • Liang Wang,
  • Wei Yang,
  • Liling Zhang,
  • Pengcheng He,
  • Shen Qian,
  • Fugen Li,
  • Meng Li,
  • Tongyu Lin

摘要

Background

Peripheral T-cell lymphoma (PTCL) is an aggressive malignancy with limited treatment options and poor prognosis, particularly for relapsed or refractory (r/r) patients. HH2853, a novel dual inhibitor of EZH1/2, has previously demonstrated clinical benefits in solid tumors. Here, we report safety and efficacy data from a phase Ib trial of HH2853 in r/r PTCL.

Methods

A phase Ib clinical trial in PTCL was conducted from July 2022–August 2023 at 15 sites in China. The study employed a dose-escalation phase (300 mg, 400 mg, and 600 mg BID) to determine the recommended phase II dosage (RP2D), followed by a dose expansion phase (300 mg and 400 mg BID). The primary endpoints were safety and the overall response rate (ORR).

Results

Thirty-four patients with various r/r PTCL histology types, a median age of 58 years, and a median of 2 prior systemic therapies were enrolled. Treatment-related adverse events (TRAEs) were observed in 92.1% of the patients, with 20.6% experiencing grade 3 TRAEs. The most common TRAEs included anemia (67.6%), thrombocytopenia (52.9%), leukopenia (44.1%), and diarrhea (38.2%). One patient (2.9%) receiving 600 mg BID experienced dose-limiting toxicity due to grade 4 thrombocytopenia. The dose of 400 mg BID was selected as the RP2D. The ORR was 67.6%, comprising 29.4% complete remission and 38.2% partial remission. As of the data cutoff in September 2024, the median follow-up period was 15.7 months, with a median duration of response of 14.8 months; overall survival had not yet been reached.

Conclusions

The selective EZH1/2 dual inhibitor HH2853 demonstrated acceptable and manageable safety profiles and promising efficacy in r/r PTCL patients, indicating its therapeutic potential for this difficult-to-treat patient population.

Trial registration

NCT04390737