BB-10901 Compound Delivers Potent Agent to CD56+ Tumors

• PRAGUE, Czech Republic—Early data from a phase I study of the targeted immunoconjugate BB-10901, also known as huN901-DM1 (ImmunoGen), has provided evidence of the drug's safety and clinical activity in patients with small-cell lung cancer (SCLC) and other CD56-positive solid tumors. An international research team reported the findings at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (abstract 649).

"It is difficult to draw any reliable conclusions from an early-phase study such as this, but we are encouraged to see early signs of activity," said principal investigator Paul Lorigan, MD, of Christie Hospital, Manchester, England. "While some tumors treated were indolent, others such as extensive SCLC were aggressive."

Dr. Lorigan conducted the dose-escalation trial with colleagues in the United Kingdom and at The University of Texas M.D. Anderson Cancer Center. He described results available from 41 patients treated in the ongoing trial who had relapsed or failed to respond to previous treatment for SCLC, lung tumors of neuroendocrine origin, and nonpulmonary small-cell carcinomas.

One patient, who suffered a recurrence of Merkel cell cancer, had a durable complete response and has remained in clinical remission for 21 months. "This patient had numerous prior relapses and had failed standard chemotherapy," he said. A second patient, who suffered a relapse of SCLC, had an unconfirmed partial response after treatment. Thirteen other patients achieved stable disease, and two of these patients remained stable for about 18 weeks.

"These results are important in that, in contrast to a prior regimen investigated in a phase I trial in the United States, significantly higher dose intensity is achieved with the current schedule," Dr. Lorigan said. "This has implications for the design of future trials, especially as the amount of the drug given is likely to be important in determining clinical response and outcome."

Although serious adverse events occurred in six patients, the trial group generally tolerated BB-10901 well, particularly compared to standard chemotherapy. "There was no clinically significant myelosuppression," Dr. Lorigan said. "Also, there was no clinical evidence of serious allergic or infusion reactions. The one side effect we have seen in higher doses is headache. This seems to be reduced if we increase the infusion time, and it may respond to other medications given with the study drug. We are investigating this further."

Pharmacokinetics measurements showed that BB-10901 attacked cells expressing CD56 more effectively at higher doses. Dr. Lorigan said the trial has not yet demonstrated a maximum tolerated dose and enrollment continues.

Two other clinical trials of BB-10901 are in progress, according to ImmunoGen. A phase II dose-escalation trial is evaluating a regimen in which the drug is administered at 60 mg/m²/d weekly for 4 weeks in a 6-week cycle to patients with relapsed SCLC or similar CD56-expressing small-cell carcinomas.

A phase I trial is evaluating BB-10901 in CD56-positive relapsed/refractory multiple myeloma patients.

The Science Behind the Study

BB-10901 (huN901-DM1) is a hybrid molecule developed by ImmunoGen to specifically target cancer cells expressing the CD56 surface molecule and deliver a cytotoxic agent. It consists of the maytansinoid cytotoxin DM1, a potent antimicrotubule agent, attached to the humanized murine monoclonal antibody huN901, using ImmunoGen's TAP (tumor-activated prodrug) technology.