Dose-escalation part of Phase I study of single-agent mosunetuzumab in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma

Jpn J Clin Oncol. 2023 Oct 4;53(10):912-921. doi: 10.1093/jjco/hyad082.

Abstract

Objective: This dose-escalation part of an ongoing Phase I study assessed the tolerability, safety and pharmacokinetics of mosunetuzumab in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL).

Methods: Mosunetuzumab was administered intravenously, with step-up dosing in a 3 + 3 design, on Days 1, 8 and 15 of Cycle 1, and Day 1 of each subsequent 21-day cycle for up to 17 cycles to patients across five cohorts with different target doses (2.8, 6.0, 13.5, 27.0 or 60.0 mg).

Results: As of 5 July 2022, 23 patients had received mosunetuzumab. The median patient age was 63.0 years, 56.5% of patients were male, and 69.6% of patients had diffuse large B-cell lymphoma, 17.4% had transformed follicular lymphoma (FL) and 13.0% had FL. The median number of prior lines of therapy was 4. Mosunetuzumab was well tolerated and there were no deaths. The most common adverse events (any grade) were neutropenia/neutrophil count decreased (47.8%) and cytokine release syndrome (34.8%). Most cytokine release syndrome events were Grade 1/2 (one Grade 3), and most occurred within 24 hours of the first dose of mosunetuzumab. The apparent half-life of mosunetuzumab was 4.1-5.0 days. Two patients achieved a complete response, and 11 patients achieved a partial response.

Conclusions: This study demonstrated that mosunetuzumab has an acceptable safety profile and antitumor activity in Japanese patients with relapsed/refractory B-cell NHL. The recommended Phase II dose of 1.0/2.0/60.0/60.0/30.0 mg was tolerable and there were no new or different safety signals compared with the global Phase I study.

Keywords: Administration; Japan; antibodies; bispecific/administration and dosage; bispecific/adverse effects; intravenous; non-Hodgkin lymphoma.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Antineoplastic Agents* / therapeutic use
  • Cytokine Release Syndrome / chemically induced
  • Cytokine Release Syndrome / drug therapy
  • East Asian People
  • Female
  • Humans
  • Lymphoma, Follicular* / drug therapy
  • Lymphoma, Non-Hodgkin* / drug therapy
  • Lymphoma, Non-Hodgkin* / pathology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy

Substances

  • Antineoplastic Agents

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