Phase I study of KW-0761, a defucosylated humanized anti-CCR4 antibody, in relapsed patients with adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma

J Clin Oncol. 2010 Mar 20;28(9):1591-8. doi: 10.1200/JCO.2009.25.3575. Epub 2010 Feb 22.


Purpose: KW-0761, a defucosylated humanized anti-CC chemokine receptor 4 (CCR4) antibody, exerts a strong antibody-dependent cellular cytotoxic effect. This phase I study assessed the safety, pharmacokinetics, recommended phase II dose and efficacy of KW-0761 in patients with relapsed CCR4-positive adult T-cell leukemia-lymphoma (ATL) or peripheral T-cell lymphoma (PTCL).

Patients and methods: Sixteen patients received KW-0761 once a week for 4 weeks by intravenous infusion. Doses were escalated, starting at 0.01, 0.1, 0.5, and finally 1.0 mg/kg by a 3 + 3 design.

Results: Fifteen patients completed the protocol treatment. Only one patient, at the 1.0 mg/kg dose, developed grade 3 dose-limiting toxicities, skin rash, and febrile neutropenia, and grade 4 neutropenia. Other treatment-related grade 3 to 4 toxicities were lymphopenia (n = 10), neutropenia (n = 3), leukopenia (n = 2), herpes zoster (n = 1), and acute infusion reaction/cytokine release syndrome (n = 1). Neither the frequency nor severity of toxicities increased with dose escalation. The maximum tolerated dose was not reached. Therefore, the recommended phase II dose was determined to be 1.0 mg/kg. No patients had detectable levels of anti-KW-0761 antibody. The plasma maximum and trough, and the area under the curve of 0 to 7 days of KW-0761, tended to increase dose and frequency dependently. Five patients (31%; 95% CI, 11% to 59%) achieved objective responses: two complete (0.1; 1.0 mg/kg) and three partial (0.01; 2 at 1.0 mg/kg) responses.

Conclusion: KW-0761 was tolerated at all the dose levels tested, demonstrating potential efficacy against relapsed CCR4-positive ATL or PTCL. Subsequent phase II studies at the 1.0 mg/kg dose are thus warranted.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Aged
  • Antibodies, Anti-Idiotypic / pharmacology
  • Antibodies, Anti-Idiotypic / therapeutic use*
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell / drug therapy*
  • Lymphoma, T-Cell, Peripheral / drug therapy*
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Receptors, CCR4 / antagonists & inhibitors*
  • Treatment Outcome


  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Receptors, CCR4
  • mogamulizumab