Phase I Study of BB-10901 (huN901-DM1) in Patients with Relapsed and Relapsed/Refractory CD56-Positive Multiple Myeloma.

Background: BB-10901 is a humanized monoclonal antibody that binds with high affinity to CD56 and is covalently linked to a novel cytotoxic maytansinoid DM1. Once bound to CD56, the conjugate is internalized and releases DM1. CD56 is expressed on a variety of tumor types such as small cell lung carcinoma, neuroendocrine tumors and hematological malignancies including multiple myeloma (MM) and acute leukemia. About 70% of MM patients have evidence of CD56 expression. Based on our preliminary results that BB-10901 has significant in vitro and in vivo anti-myeloma activity in a murine model, we have now initiated a phase I clinical study.

Objectives: To determine the maximum tolerated dose (MTD), the dose limiting toxicities (DLTs), and pharmacokinetics (PK) of BB-10901 given on a weekly schedule.

Methods: Relapsed or relapsed/refractory MM patients who have failed at least one prior therapy and have CD56 expressing myeloma received a single IV infusion of BB-10901 on 2 consecutive weeks every 3 weeks. Subjects are enrolled in cohorts of 3 at each dose level. The starting dose was 40 mg/m²/week based on experience from a prior phase I trial in solid tumors.

Results: Five patients have received BB-10901, 3 at 40 mg/m²/week and 2 at 60 mg/m²/week. No patients have experienced DLTs and no serious adverse events related to study drug were observed. In addition, no patients have experienced serious hypersensitivity reactions or evidence of HAHA or HADA formation. Our preliminary PK findings demonstrate that there is no evidence of accumulation of BB-10901. Detailed PK analysis and updated toxicity and efficacy data will be presented. Immunohistochemistry performed on marrow aspirates about 24 hours after huN901-DM1 infusion at 40 mg/m² confirmed the presence of huN901-DM1 on myeloma cells in the marrow. Two patients treated at 60 mg/m²/week and who had failed multiple prior therapies including bortezomib, thalidomide and/or lenalidomide demonstrated anti-tumor response with a decrease in M proteins of 90% and 33%, respectively. Both patients received a fifth cycle of therapy and one continues on study.

Conclusions: This phase I study provides preliminary evidence of safety and clinical activity of BB-10901 in patients with CD56-positive MM who have failed established MM treatments. Targeting of BB-10901 to myeloma cells in the marrow was confirmed. The MTD is not yet defined and enrollment is ongoing.