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Invest New Drugs. 2014 Dec;32(6):1213-25. doi: 10.1007/s10637-014-0125-2. Epub 2014 Jun 15.

Phase 1b study of otlertuzumab (TRU-016), an anti-CD37 monospecific ADAPTIR™ therapeutic protein, in combination with rituximab and bendamustine in relapsed indolent lymphoma patients.

Author information

1
Department of Medicine, University of Washington, Box 358081, 825 Eastlake Ave E.,, MS G3200, Seattle, WA, USA, agopal@u.washington.edu.

Abstract

PURPOSE:

CD37 is cell surface tetraspanin present on normal and malignant B cells. Otlertuzumab (TRU-016) is a novel humanized anti-CD37 protein therapeutic that triggers direct caspase independent apoptosis of malignant B cells and induces antibody-dependent cell-mediated cytotoxicity. This study evaluated the safety, pharmacokinetics, and efficacy of otlertuzumab administered in combination with rituximab and bendamustine to patients with relapsed, indolent B-cell non-Hodgkin Lymphoma (NHL).

METHODS:

Patients with relapsed or refractory NHL received otlertuzumab (10 or 20 mg/kg) intravenously (IV) on days 1 and 15, bendamustine (90 mg/m(2)) on days 1 and 2, and rituximab (375 mg/m(2)) on day 1 for up to six 28 day cycles. Responses were determined using standard criteria.

RESULTS:

Twelve patients were treated with 6 patients at each dose level; median age was 57 years (range, 51-79), and median number of prior regimens was 3 (range, 1-4). All patients had relapsed after prior rituximab including 7 refractory to their most recent previous treatment. In the 10 and 20 mg/kg dose cohorts, the mean half-life was 8 and 10 days following the first dose, and 12 or 14 days following 12 doses of otlertuzumab, respectively. Overall response rate was 83% (10/12) with 4 CRs (32%). The most frequent adverse events were neutropenia, nausea, fatigue, leukopenia, and insomnia; most were grade 1 or 2.

CONCLUSIONS:

Otlertuzumab in combination with rituximab and bendamustine was well tolerated and induced responses in the majority of patients with relapsed indolent B-NHL. NCI Clinical Trials Network registration: NCT01317901.

PMID:
24927856
PMCID:
PMC4229440
DOI:
10.1007/s10637-014-0125-2
[Indexed for MEDLINE]
Free PMC Article

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