Phase I/II Clinical Trial Results

John P. Leonard¹, Morton Coleman¹, Jamie C. Ketas¹, Amy Chadburn², Richard Furman¹, Michael W. Schuster¹, Eric J. Feldman¹, Michelle Ashe¹, Stephen J. Schuster³, William A. Wegener⁴, Hans J. Hansen⁴, Heather Ziccardi⁴, Michael Eschenberg⁵, Urte Gayko⁵, Scott Z. Fields⁶, Alessandra Cesano⁵ and David M. Goldenberg^4,7

¹ Division of Hematology and Oncology and ² Department of Pathology, Center for Lymphoma and Myeloma, Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, New York; ³ University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania; ⁴ Immunomedics, Inc., Morris Plains, New Jersey; ⁵ Amgen Inc., Thousand Oaks, California; ⁶ Eisai Medical Research, Teaneck, New Jersey; and ⁷ Center for Molecular Medicine and Immunology, Garden State Cancer Center, Belleville, New Jersey

ABSTRACT

Purpose: We conducted a single-center, dose-escalation study evaluating the safety, pharmacokinetics, and efficacy of epratuzumab, an anti-CD22 humanized monoclonal antibody, in patients with aggressive non-Hodgkin’s lymphoma.

Experimental Design: Epratuzumab was administered once weekly for 4 weeks at 120-1000-mg/m² doses to 56 patients [most (n = 35) with diffuse large B-cell lymphoma].

Results: Patients were heavily pretreated (median, 4 prior therapies), 25% received prior high-dose chemotherapy with stem cell transplant, and 84% had bulky disease (5 cm). Epratuzumab was well tolerated, with no dose-limiting toxicity. Most (95%) infusions were completed within 1 h. The mean serum half-life was 23.9 days. Across all dose levels and histologies, objective responses (ORs) were observed in five patients (10%; 95% confidence interval, 3–21%), including three complete responses. In patients with diffuse large B-cell lymphoma, 15% had ORs. Overall, 11 (20%) patients experienced some tumor mass reduction. Median duration of OR was 26.3 weeks, and median time to progression for responders was 35 weeks. Two responses are ongoing at 34 months, including one rituximab-refractory patient.

Conclusions: These data demonstrate that epratuzumab has a good safety profile and exerts antitumor activity in aggressive non-Hodgkin’s lymphoma at doses of 240 mg/m², thus warranting further evaluation in this clinical setting.

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