Phase II trial of BB-10901 (huN901-DM1) given weekly for four consecutive weeks every 6 weeks in patients with relapsed SCLC and CD56-positive small cell carcinoma

Abstract

7159 Background: BB-10901 is an immunoconjugate created by conjugation of the cytotoxic maytansinoid drug DM1 to a humanized version of the murine monoclonal antibody N901. BB-10901 binds with high affinity to CD56. The latter is expressed on a variety of solid tumors including small cell lung carcinoma. Methods: A phase I dose escalating study was conducted in patients with small cell lung carcinoma and other CD56-positive solid tumors. The maximum tolerated dose was defined as 60 mg/m2/week given as an IV infusion for four consecutive weeks every six weeks. A phase II extension of this trial is underway in which patients with relapsed small cell lung carcinoma or with relapsed CD56+ non-pulmonary small cell carcinoma are treated on this regimen. The Phase II extension consists of two stages. 14 patients are initially enrolled. The study is expanded to 35 patients if an objective response is observed among the initial 14 patients. Results: 10 patients have been treated on the Phase II extension of the study. One patient had a serious adverse event consisting of aseptic meningitis. Symptoms resolved within one week. No other drug related SAEs have occurred among the ten patients. Preliminary evaluation reveals no evidence of cardiac, thyroid, or adrenal dysfunction secondary to BB-10901. Initial pharmacokinetic findings demonstrate an increase in both t½ (terminal half life) and AUC (Area Under Curve) in Week 2 compared to Week 1 in two patients whose data are available. The t½ increased from 8.4 to 11.2 hours (h) and from 9.2 to 14.3 h from Week 1 to Week 2, respectively in the two patients. Evidence of clinical activity was noted in three patients. A patient with relapsed small cell lung carcinoma has preliminary evidence of a partial response. A patient with relapsed small cell carcinoma had a non-sustained partial response. A third patient with relapsed SCLC had a minor response. Conclusions: The study provides evidence of safety and clinical activity of BB-10901. The prolongation in t½ that occurred after initial dosing is consistent with saturation of CD56 positive sites such as NK cells. The study will be expanded to 35 patients upon confirmation of the partial response. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ImmunoGen ImmunoGen