Phase II trial of huN901-DM1 in patients with relapsed small cell lung cancer (SCLC) and CD56-positive small cell carcinoma

Autor:	Frank V. Fossella, P. Fidias, J. McCann, R. Raju, Anthony W. Tolcher, Miguel A. Villalona-Calero, R. J. Fram, R. Guild, S. Zildjian
Rok vydání:	2007
Předmět:	Cancer Research medicine.medical_specialty business.industry HuN901-DM1 medicine.disease Small-cell carcinoma Gastroenterology Surgery Immunoconjugate Oncology Internal medicine medicine In patient Adverse effect business Every Six Weeks Relapsed Small Cell Lung Cancer Multiple myeloma
Zdroj:	Journal of Clinical Oncology. 25:18084-18084
ISSN:	1527-7755 0732-183X
DOI:	10.1200/jco.2007.25.18_suppl.18084
Popis:	18084 Background: HuN901-DM1, a humanized antibody-maytansinoid immunoconjugagte, binds to CD56 which is expressed in almost all cases of SCLC as well as in other small cell carcinomas (SCC), neuroendocrine carcinomas, and multiple myeloma. The immunoconjugate binds to its target antigen, is internalized, then releases DM1. Methods: Patients with relapsed SCLC and CD56- positive SCC of other sites are treated with huN901-DM1 given as an intravenous infusion at 60 mg/m2/week for four consecutive weeks every six weeks. The study consists of two stages. Fourteen patients were initially enrolled. The occurrence of an objective response among the initial 14 patients prompted expansion to a total of 35 evaluable patients. Clinical response is evaluated by RECIST criteria. Results: To date, thirty patients have been treated in the study. Four patients experienced drug related serious adverse events (SAEs). Three patients had severe headache after the initial infusion of study drug. Symptoms markedly improved after 24 hours and then completely resolved. Severe headaches did not occur in subsequent patients who were pre-medicated with steroids prior to all infusions. A patient with a history of diabetic neuropathy and prior cisplatin treatment had grade 4 hyperesthesia. There was no evidence of clinically significant myelosuppression. HuN901-DM1 generally was well tolerated and no serious infusion reactions occurred. Preliminary pharmacokinetic (PK) data reveal no prolongation of terminal half-life of the immunoconjugate when PK parameters are compared from the first and fourth dose of cycle 1. Further, there was no evidence of antibody formation to the antibody component (HAHA) or drug component (HADA) of huN901-DM1. One patient (pt) with relapsed, SCLC had an objective partial response lasting 18 weeks and a pt with cervical SCC had an unconfirmed partial response. Stable disease was observed in five patients and lasted about 6 (3 pts), 12 (1 pt), and 18 weeks (1 pt). Conclusions: The study provides evidence of clinical activity and safety of huN901-DM1. Pre-medication with steroids appears effective in preventing severe headaches. Enrollment of additional patients to the study is planned. No significant financial relationships to disclose.
Databáze:	OpenAIRE
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