Phase I multidose-escalation study of the anti-CD19 maytansinoid immunoconjugate SAR3419 administered by intravenous infusion every 3 weeks to patients with relapsed/refractory B-cell lymphoma

Anas Younes*, Stella Kim, Jorge Romaguera, Amanda Copeland, Silvanade De Castro Farial, Larry W. Kwak, Luis Fayad, Frederick Hagemeister, Michelle Fanale, Sattva Neelapu, John M. Lambert, Rodica Morariu-Zamfir, Sandrine Payrard, Leo I. Gordon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

Purpose: We determine the maximum-tolerated dose (MTD), pharmacokinetics, safety, and preliminary efficacy of SAR3419, an antibody-drug conjugate targeting CD19, in a first-in-man phase I clinical trial in patients with relapsed lymphoma. Patients and Methods: Patients with relapsed CD19+ B-cell lymphoma were treated with escalating doses of SAR3419 given by intravenous infusion once every 21 days. Results: Thirty-nine patients were treated on seven dose levels ranging from 10 to 270 mg/m 2. The median number of prior treatment regimens was four (range, 1 to 9), and 11 patients had prior autologous or allogeneic stem-cell transplantation. The dose-limiting toxicities were reversible severe blurred vision associated with microcystic epithelial corneal changes reported in six patients and neuropathy in one patient. The MTD was 160 mg/m 2 once every 21 days. Hematologic and hepatic toxicities were predominantly grade 1 or 2 in severity. A total of 35 patients have completed at least two cycles of treatment and were evaluable for tumor response. Twenty-six patients (74%) demonstrated reduction in their tumor size; six of those patients achieved partial or complete remissions. Seven (47%) of 15 patients with rituximab-refractory disease demonstrated reduction in their tumor sizes. The pharmacokinetic profile of SAR3419 is characterized by linear kinetics, low clearance from 0.2 to 0.6 L/d/m 2, and an elimination half-life in the range of 3 to 7 days. Conclusion: Using an every 3-week-schedule of SAR3419 for six cycles, the MTD is 160 mg/m 2. SAR3419 can be safely administered to patients with relapsed B-cell lymphoma and demonstrates promising clinical activity, including patients who were refractory to rituximab.

Original languageEnglish (US)
Pages (from-to)2776-2782
Number of pages7
JournalJournal of Clinical Oncology
Volume30
Issue number22
DOIs
StatePublished - Aug 1 2012

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Phase I multidose-escalation study of the anti-CD19 maytansinoid immunoconjugate SAR3419 administered by intravenous infusion every 3 weeks to patients with relapsed/refractory B-cell lymphoma'. Together they form a unique fingerprint.

Cite this