{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:44:46Z","timestamp":1791305086522,"version":"4.3.1"},"reference-count":41,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2010,3,20]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2009.25.3575","type":"journal-article","created":{"date-parts":[[2010,2,23]],"date-time":"2010-02-23T03:47:24Z","timestamp":1266896844000},"page":"1591-1598","source":"Crossref","is-referenced-by-count":303,"title":["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"],"prefix":"10.1200","volume":"28","author":[{"given":"Kazuhito","family":"Yamamoto","sequence":"first","affiliation":[{"name":"From Department of Hematology and Cell Therapy, Aichi Cancer Center; Department of Clinical Pathophysiology and Department of Infectious Diseases, Nagoya University Graduate School of Medicine; Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital, Nagoya; Department of Clinical Pathology and Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagaya; 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