A phase I weekly dosing study of brentuximab vedotin in patients with relapsed/refractory CD30-positive hematologic malignancies

Michelle A. Fanale, Andres Forero-Torres, Joseph D. Rosenblatt, Ranjana H. Advani, Anna R. Franklin, Dana A. Kennedy, Tae H. Han, Eric L. Sievers, Nancy L. Bartlett

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165 Scopus citations

Abstract

Purpose: The antibody-drug conjugate (ADC) brentuximab vedotin comprises a CD30-directed antibody covalently attached to the potent antimicrotubule agent monomethyl auristatin E (MMAE) via a protease-cleavable linker. This study explored the safety, maximum-tolerated dose (MTD), and activity of weekly dosing of brentuximab vedotin in patients with relapsed or refractory CD30-positive hematologic malignancies. Experimental Design: In this phase I dose-escalation study, brentuximab vedotin was administered intravenously on Days 1, 8, and 15, of each 28-day cycle at doses ranging from 0.4 to 1.4 mg/kg. Forty-four patients were enrolled: 38 with Hodgkin lymphoma, five with systemic anaplastic large cell lymphoma, and one with peripheral T-cell lymphoma not otherwise specified. Doses were escalated in increments of 0.2 mg/kg until dose-limiting toxicity (DLT) was observed. Patients were monitored for antitherapeutic antibodies and pharmacokinetic parameters. Antitumor assessments were carried out every two cycles. Results: The MTD was 1.2 mg/kg. The most commonadverse events were peripheral sensory neuropathy, fatigue, nausea, diarrhea, arthralgia, and pyrexia; and the majority of events were mild to moderate in severity. Tumor regression occurred in 85% of patients and the overall objective response rate was 59% (n = 24), with 34% (n = 14) complete remissions. The median duration of response was not reached at a median follow-up of 45 weeks on study. Conclusions: Weekly administration of brentuximab vedotin resulted in tumor regression and durable remissions in patients with CD30-positive malignancies. This ADC was associated with manageable toxicity, including peripheral neuropathy. Further study in CD30-positive malignancies is warranted.

Original languageEnglish (US)
Pages (from-to)248-255
Number of pages8
JournalClinical Cancer Research
Volume18
Issue number1
DOIs
StatePublished - Jan 1 2012

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Fanale, M. A., Forero-Torres, A., Rosenblatt, J. D., Advani, R. H., Franklin, A. R., Kennedy, D. A., Han, T. H., Sievers, E. L., & Bartlett, N. L. (2012). A phase I weekly dosing study of brentuximab vedotin in patients with relapsed/refractory CD30-positive hematologic malignancies. Clinical Cancer Research, 18(1), 248-255. https://doi.org/10.1158/1078-0432.CCR-11-1425