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Title: IMGN901 Is Well Tolerated, Shows Clinical Activity in Patients With CD56-Positive Solid Tumours: Presented at EORTC-NCI-AACR

"IMGN901 Is Well Tolerated, Shows Clinical Activity in Patients With CD56-Positive Solid Tumours: Presented at EORTC-NCI-AACR"

By Chris Berrie GENEVA -- October 27, 2008 -- A conjugate of the cytotoxic maytansinoid DM1 and the human N901 antibody, known in development as IMGN901, is generally well tolerated and shows clinical activity in patients with CD56-positive solid tumours. An early study of IMGN901 was presented here on October 24 at the 20th International Symposium of the European Organisation for Research and Treatment of Cancer (EORTC), the National Cancer Institute (NCI), and the American Association for Cancer Research (AACR). IMGN901 is designed to kill CD56-overexpressing cells, noted coinvestigator Alberto Qin, MD, PhD, ImmunoGen Inc., Waltham, Massachusetts, including those found in small-cell lung carcinomas (SCLCs), non-pulmonary small-cell carcinomas, neuroendocrine tumours, and multiple myelomas. The primary objective of this study was to determine the safety parameters and maximum tolerated dose for IMGN901 when administered by daily intravenous (IV) infusion for 3 consecutive days every 21 days. Secondary objectives included IMGN901 pharmacokinetics and antineoplastic activity. All subjects had histologically or cytologically proven SCLC or other CD56-positive solid tumours, with generally 1 to 3 previous chemotherapies. The Eastern Cooperative Oncology Group performance status (ECOG-PS) was set for 0 to 2, with laboratory criteria specified as: absolute neutrophils >=1.5x 10[⁹/L; haemoglobin >=10 g/dL; platelets >=100x 10⁹/L; creatinine <=1.5x upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=2.5x ULN; and bilirubin <=3x ULN.

In total, 45 patients (median age: 55 years) were enrolled. Their main baseline clinical characteristics included 1 or 2 prior chemotherapy regimens (89%) and prior radiotherapy (61%). Their tumour types were SCLC (38%), neuroendocrine (31%), and other CD56-positive tumours (31%).

Clinical activity of IMGN901 treatment saw tumour shrinkage in 9 (29%) of 31 response-evaluable patients. As the researchers specifically noted, one patient with metastatic Merkel cell carcinoma had a durable complete response with clinical remission for over 3 years. There was also one unconfirmed partial response and 14 patients with stable disease lasting 5 to 18 weeks.

The most common post-treatment grade 1/2 adverse events were headache, fatigue, nausea, vomiting, and peripheral sensory neuropathy. There were no serious infusion reactions or evidence of hypersensitivity and no clinically significant myelosuppression.

Finally, with IMGN901 showing preliminary evidence of safety and clinical activity in this trial, the researchers also noted that prophylactic measures on the day before and the day of IMGN901 treatment, and a decreased infusion rate of 1 mg/mL, appear to prevent occurrence of severe headache.

Individuals were excluded from this study who had any of the following: recent myocardial infarction; unstable angina, uncontrolled chronic heart failure, or uncontrolled arrhythmia; history of multiple sclerosis or other demyelinating disease; any central nervous system (CNS) injury with residual neurological deficit; serious infection or other concomitant illness; previous monoclonal antibody therapy; or known CNS metastases.

Funding for this study was provided by ImmunoGen Inc.

[Presentation title: Phase 1 Study of IMGN901 (BB-10901) Given on a Daily x3 Schedule in Patients With CD56-Positive Solid Tumours. Abstract 510]

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