Abstract B237: Clinical experience of IMGN901 (BB-10901, huN901-DM1) in patients with Merkel cell carcinoma (MCC)
Authors: Woll Penella , Lorigan Paul , O'Brien Mary , Villalona-Calero Miguel , O'Keeffe Jessica , Qin Albert , O'Leary James , Fossella Frank 
Published: June 2012

Abstract
Background: MCC is a neuroendocrine cancer of the skin that predominantly occurs in older individuals of northern European ancestry. While localized disease can often be treated with surgery and radiation therapy, there is a need for effective, well-tolerated chemotherapeutic options for patients with progressive or metastatic disease. Among patients with metastatic MCC, overall 5-year survival rate is 11% and median survival is in the range of 7 to 9 months. To date, no chemotherapeutic agent has been able to demonstrate a significant improvement in survival. Toxicity also is a major concern with these older patients.
IMGN901 is a novel CD56-targeting anticancer agent. CD56 is expressed on virtually all MCC tumors. IMGN901 consists of a potent maytansinoid cytotoxic agent, DM1, attached to a CD56-binding monoclonal antibody, huN901, using an engineered linker. Once bound to CD56, IMGN901 is internalized into the cancer cell and the DM1 is released to kill the cell via inhibition of the polymerization of tubulin.
Objective: Study 002 is an ongoing phase I trial established to determine the maximum tolerated dose (MTD), pharmacokinetics (PK) and activity of IMGN901 in patients with CD56-expressing solid tumors, including patients with MCC.
Methods: IMGN901 is administered intravenously as monotherapy daily for 3 consecutive days every 3 weeks.
Results: Six patients with MCC have been enrolled in Study 002 in addition to patients with other types of CD56+ solid tumors. Clinical benefit has been observed in 3 of these 6 patients including one complete response (CR), one partial response (PR) and one stable disease (SD). The patient who experienced a CR has remained disease free for more than 4 years. The patient who experienced a PR received 1 cycle of IMGN901 treatment, but had a serious adverse event and declined further treatment. This patient had sustained clinical benefit for more than 5 months, including additional tumor shrinkage. The patient who experienced SD entered Study 002 with bone metastases and had received 3 prior therapies. This patient had SD lasting approximately 3 months. Overall, a clinical benefit rate (CR+PR+SD) of 50% has been observed. The 6 MCC patients received IMGN901 at doses ranging from 36 to 75 mg/m2/day. The MTD of IMGN901 has not been defined in Study 002 and a dose level of 94 mg/m2/day will be evaluated next. Earlier this year, we reported pooled data from two studies in CD56+ solid tumors summarizing the encouraging experience with IMGN901 for the treatment of small-cell lung cancer (SCLC). SCLC and MCC have shared morphologic characteristics and a common clinical course.
Conclusion: There are encouraging findings to date with IMGN901 for the treatment of MCC. The findings are supportive of the initial findings with the compound for the treatment of SCLC and vice versa.
Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B237.