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Background <p>Bispecific antibodies engaging CD3 have transformed the treatment landscape of B-cell malignancies but remain constrained by T-cell overactivation and cytokine release. Here, we describe PSB202, a first-in-class bifunctional antibody co-targeting CD20 and CD37 to deplete malignant B cells independently of T-cell engagement.</p> Methods <p>In this multicenter, open-label phase Ia trial (NCT05003141), adults with relapsed or refractory (R/R) CD20⁺ B-cell non-Hodgkin lymphoma (B-NHL) received escalating doses of PSB202 from 12 to 300&#xa0;mg. Primary endpoints were dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD). Secondary endpoints were safety, pharmacokinetics, pharmacodynamics, and efficacy.</p> Results <p>Fifteen heavily-pretreated patients were enrolled, with a median age of 67.7&#xa0;years (range, 54–78). One DLT of grade 4 neutropenia occurred at 100&#xa0;mg. MTD was not reached. PSB202 showed a manageable safety profile, with grade ≥ 3 neutropenia and leukopenia both occurring in 60% of patients. The overall response rate was 30% in 10 evaluable patients, including one complete response at 300&#xa0;mg. PSB202 achieved sustained B-cell depletion and induced IFN-γ release without cytokine release syndrome. Single-cell sequencing revealed different immune microenvironments in responders and non-responders, and the treatment also induced alterations.</p> Conclusions <p>PSB202 may represent a novel dual-targeting strategy that possibly mitigates CD3-related toxicity while promoting cytotoxic immune activation. These findings support further clinical development of PSB202 as an off-the-shelf therapeutic alternative for R/R B-NHL.</p> Trial registration <p>This study was registered with ClinicalTrials.gov, NCT05003141.</p>

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A first-in-class bifunctional antibody targeting CD20 and CD37 remodels the immune microenvironment in relapsed or refractory B-cell malignancies

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月29日

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  • Li Wang,
  • Jiaying Liu,
  • Keshu Zhou,
  • Zengjun Li,
  • Yun Zeng,
  • Ying Qian,
  • Yuping Sun,
  • Hui Wu,
  • Lindsay Roerker,
  • Peter Tan,
  • Chen Ma,
  • Liwei Zhou,
  • Xianlin Duan,
  • Xiaoyan Kang,
  • Wei-Li Zhao

摘要

Background

Bispecific antibodies engaging CD3 have transformed the treatment landscape of B-cell malignancies but remain constrained by T-cell overactivation and cytokine release. Here, we describe PSB202, a first-in-class bifunctional antibody co-targeting CD20 and CD37 to deplete malignant B cells independently of T-cell engagement.

Methods

In this multicenter, open-label phase Ia trial (NCT05003141), adults with relapsed or refractory (R/R) CD20⁺ B-cell non-Hodgkin lymphoma (B-NHL) received escalating doses of PSB202 from 12 to 300 mg. Primary endpoints were dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD). Secondary endpoints were safety, pharmacokinetics, pharmacodynamics, and efficacy.

Results

Fifteen heavily-pretreated patients were enrolled, with a median age of 67.7 years (range, 54–78). One DLT of grade 4 neutropenia occurred at 100 mg. MTD was not reached. PSB202 showed a manageable safety profile, with grade ≥ 3 neutropenia and leukopenia both occurring in 60% of patients. The overall response rate was 30% in 10 evaluable patients, including one complete response at 300 mg. PSB202 achieved sustained B-cell depletion and induced IFN-γ release without cytokine release syndrome. Single-cell sequencing revealed different immune microenvironments in responders and non-responders, and the treatment also induced alterations.

Conclusions

PSB202 may represent a novel dual-targeting strategy that possibly mitigates CD3-related toxicity while promoting cytotoxic immune activation. These findings support further clinical development of PSB202 as an off-the-shelf therapeutic alternative for R/R B-NHL.

Trial registration

This study was registered with ClinicalTrials.gov, NCT05003141.