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Introduction <p>Rocbrutinib is a fourth-generation Bruton’s tyrosine kinase (BTK) inhibitor that binds covalently to the wild type BTK and non-covalently to the cysteine&#xa0;481 mutant variant. This phase I study evaluated the pharmacokinetics (PK), safety, and efficacy of rocbrutinib in Chinese patients with relapsed or refractory (R/R) non-germinal center B cell-like (non-GCB) diffuse large B cell lymphoma (DLBCL).</p> Methods <p>Eligible participants were adults with non-GCB DLBCL and had received ≥ 2 prior lines of systemic therapy, including an anti-CD20 antibody-based regimen. Patients received rocbrutinib at 100, 150, 200 or 300&#xa0;mg once daily (QD) as single agent till disease progression or unacceptable toxicity. Response was evaluated using computerized tomography (CT) and positron emission tomography (PET)-CT at the protocol-defined timepoints by the investigators. PK samples and adverse events were collected per protocol.</p> Results <p>A total of 45 patients were enrolled, of whom 44.4% had received ≥ 3 lines of therapy. The overall response rate (ORR) was 57.8% [95% confidence interval (CI): 42.2, 72.3], and the complete response (CR) rate was 33.3% (95% CI 20.0, 49.0). In the ≥ 200&#xa0;mg QD cohort (<i>n</i> = 18), the ORR was 72.2% (95% CI 46.5, 90.3) and the CR rate was 44.4% (95% CI 21.5, 69.2). Treatment-emergent adverse events (TEAEs) were reported in 97.8% patients, ≥ grade 3 TEAEs in 51.1% patients. Due to TEAEs, 2 patients (4.4%) with dose reduction and 1 (2.2%) discontinued study treatment, respectively. No atrial fibrillation/flutter was reported. In the ≥ 200&#xa0;mg QD cohort, the safety profile was consistent with the overall population.</p> Conclusion <p>Rocbrutinib demonstrated promising efficacy and favorable tolerability profile in heavily pre-treated R/R non-GCB DLBCL. A 200&#xa0;mg QD dose was selected as recommended phase 2 dose for monotherapy. A randomized phase II clinical trial in this population is currently enrolling.</p> Trial Registration <p>ClinicalTrials.gov identifier, NCT04993690</p>

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Rocbrutinib, a Highly Selective Fourth-Generation Covalent and Noncovalent BTK Inhibitor, in R/R Non-GCB DLBCL: Efficacy and Safety from a Phase I Study

  • 期刊论文

  • 发表日期：

    2026年7月24日

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  • Ningjing Lin,
  • Qingqing Cai,
  • Keshu Zhou,
  • Xiuhua Sun,
  • Kaiyang Ding,
  • Lei Zhang,
  • Zhengming Jin,
  • Ming Jiang,
  • Zhigang Peng,
  • Lanfang Li,
  • Wei Yang,
  • Min Zhou,
  • Yuankai Shi,
  • Zheng Wang,
  • Nawei Liu,
  • Yejiang Lou,
  • Yue Shen,
  • Yi Chen,
  • Fenlai Tan,
  • Yuqin Song,
  • Jun Zhu

摘要

Introduction

Rocbrutinib is a fourth-generation Bruton’s tyrosine kinase (BTK) inhibitor that binds covalently to the wild type BTK and non-covalently to the cysteine 481 mutant variant. This phase I study evaluated the pharmacokinetics (PK), safety, and efficacy of rocbrutinib in Chinese patients with relapsed or refractory (R/R) non-germinal center B cell-like (non-GCB) diffuse large B cell lymphoma (DLBCL).

Methods

Eligible participants were adults with non-GCB DLBCL and had received ≥ 2 prior lines of systemic therapy, including an anti-CD20 antibody-based regimen. Patients received rocbrutinib at 100, 150, 200 or 300 mg once daily (QD) as single agent till disease progression or unacceptable toxicity. Response was evaluated using computerized tomography (CT) and positron emission tomography (PET)-CT at the protocol-defined timepoints by the investigators. PK samples and adverse events were collected per protocol.

Results

A total of 45 patients were enrolled, of whom 44.4% had received ≥ 3 lines of therapy. The overall response rate (ORR) was 57.8% [95% confidence interval (CI): 42.2, 72.3], and the complete response (CR) rate was 33.3% (95% CI 20.0, 49.0). In the ≥ 200 mg QD cohort (n = 18), the ORR was 72.2% (95% CI 46.5, 90.3) and the CR rate was 44.4% (95% CI 21.5, 69.2). Treatment-emergent adverse events (TEAEs) were reported in 97.8% patients, ≥ grade 3 TEAEs in 51.1% patients. Due to TEAEs, 2 patients (4.4%) with dose reduction and 1 (2.2%) discontinued study treatment, respectively. No atrial fibrillation/flutter was reported. In the ≥ 200 mg QD cohort, the safety profile was consistent with the overall population.

Conclusion

Rocbrutinib demonstrated promising efficacy and favorable tolerability profile in heavily pre-treated R/R non-GCB DLBCL. A 200 mg QD dose was selected as recommended phase 2 dose for monotherapy. A randomized phase II clinical trial in this population is currently enrolling.

Trial Registration

ClinicalTrials.gov identifier, NCT04993690