A randomized, multicenter study to determine the safety and efficacy of the immunoconjugate SGN-15 plus docetaxel for the treatment of non-small cell lung carcinoma

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2006-10, Vol.54 (1), p.69-77
• Main Authors: Ross, Helen J., Hart, Lowell L., Swanson, Paul M., Rarick, Mark U., Figlin, Robert A., Jacobs, Andrew D., McCune, David E., Rosenberg, Arthur H., Baron, Ari D., Grove, Laurie E., Thorn, Michael D., Miller, Dennis M., Drachman, Jonathan G., Rudin, Charles M.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Animals; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - therapeutic use; Antineoplastic Agents, Phytogenic - adverse effects; Antineoplastic Agents, Phytogenic - pharmacokinetics; Antineoplastic Agents, Phytogenic - therapeutic use; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - drug therapy; Female; Humans; Immunoconjugate; Immunoconjugates - adverse effects; Immunoconjugates - pharmacokinetics; Immunoconjugates - therapeutic use; Lewis Y; Lung Neoplasms - drug therapy; Male; Medical sciences; Mice; Middle Aged; Monoclonal antibody; NSCLC; Pneumology; Quality of Life; SGN-15; Survival Rate; Targeted therapy; Taxoids - adverse effects; Taxoids - pharmacokinetics; Taxoids - therapeutic use; Treatment Outcome; Tumors of the respiratory system and mediastinum; United States
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2006.05.020

Chemotherapy prolongs survival and improves quality of life (QOL) for good performance status (PS) patients with advanced non-small cell lung cancer (NSCLC). Targeted therapies may improve chemotherapy effectiveness without worsening toxicity. SGN-15 is an antibody–drug conjugate (ADC), consisting of a chimeric murine monoclonal antibody recognizing the Lewis Y (Le y) antigen, conjugated to doxorubicin. Le y is an attractive target since it is expressed by most NSCLC. SGN-15 was active against Le y-positive tumors in early phase clinical trials and was synergistic with docetaxel in preclinical experiments. This Phase II, open-label study was conducted to confirm the activity of SGN-15 plus docetaxel in previously treated NSCLC patients. Sixty-two patients with recurrent or metastatic NSCLC expressing Le y, one or two prior chemotherapy regimens, and PS ≤ 2 were randomized 2:1 to receive SGN-15 200 mg/m 2/week with docetaxel 35 mg/m 2/week (Arm A) or docetaxel 35 mg/m 2/week alone (Arm B) for 6 of 8 weeks. Intrapatient dose-escalation of SGN-15 to 350 mg/m 2 was permitted in the second half of the study. Endpoints were survival, safety, efficacy, and quality of life. Forty patients on Arm A and 19 on Arm B received at least one treatment. Patients on Arms A and B had median survivals of 31.4 and 25.3 weeks, 12-month survivals of 29% and 24%, and 18-month survivals of 18% and 8%, respectively. Toxicity was mild in both arms. QOL analyses favored Arm A. SGN-15 plus docetaxel is a well-tolerated and active second and third line treatment for NSCLC patients. Ongoing studies are exploring alternate schedules to maximize synergy between these agents.