A phase 1 study evaluating the safety and tolerability of otlertuzumab, an anti-CD37 mono-specific ADAPTIR therapeutic protein in chronic lymphocytic leukemia

• Published in: Blood Vol. 123; no. 9; pp. 1302 - 1308
• Main Authors: Byrd, John C., Pagel, John M., Awan, Farrukh T., Forero, Andres, Flinn, Ian W., Deauna-Limayo, Delva P., Spurgeon, Stephen E., Andritsos, Leslie A., Gopal, Ajay K., Leonard, John P., Eisenfeld, Amy J., Bannink, Jeannette E., Stromatt, Scott C., Furman, Richard R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.02.2014; American Society of Hematology
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antigens, Neoplasm - immunology; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Clinical Trials and Observations; Female; Humans; Immunoglobulin G - adverse effects; Immunoglobulin G - therapeutic use; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Male; Maximum Tolerated Dose; Middle Aged; Protein Engineering; Recombinant Fusion Proteins - adverse effects; Recombinant Fusion Proteins - therapeutic use; Tetraspanins - immunology; Treatment Outcome
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2013-07-512137

Otlertuzumab is a novel humanized anti-CD37 protein therapeutic. This study evaluated the safety of otlertuzumab administered intravenously to patients with chronic lymphocytic leukemia (CLL). Otlertuzumab was administered weekly for up to 8 weeks followed by 1 dose per month for 4 months ranging from 0.03 to 20 mg/kg in the dose-escalation phase and 10 to 30 mg/kg in the dose-expansion phase. Responses were determined by using the 1996 National Cancer Institute (NCI-96) and 2008 International Workshop on Chronic Lymphocytic Leukaemia (IWCLL) criteria. Fifty-seven patients were treated in the dose-escalation phase and 26 in the dose-expansion phase. A maximum-tolerated dose was not identified. Response occurred in 19 (23%) of 83 treated patients by NCI-96 criteria. All responses were partial and occurred more commonly in patients with symptomatic untreated CLL (6/7) or 1 to 2 prior therapies (12/28) vs 3 or more therapies (1/48). Twenty percent (12/61) with serial computed tomography scan assessment had a response per IWCLL criteria. The most frequent adverse events were infusion reactions, fatigue, nausea, and diarrhea and were not dose related. Otlertuzumab was well tolerated, and modest clinical activity was observed. Otlertuzumab warrants further evaluation in combination with other agents for the treatment of CLL. This trial was registered at www.clinicaltrials.gov as #NCT00614042. •Otlertuzumab (formerly TRU-016) has modest single-agent activity in symptomatic treated and untreated CLL.•Otlertuzumab demonstrates an acceptable safety profile, providing rationale for combination with other effective CLL therapies.