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

Summary Purpose 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. Experimental design 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 200mg/m 2 /week with docetaxel 35mg/m 2 /week (Arm A) or docetaxel 35mg/m 2 /week alone (Arm B) for 6 of 8 weeks. Intrapatient dose-escalation of SGN-15 to 350mg/m 2 was permitted in the second half of the study. Endpoints were survival, safety, efficacy, and quality of life. Results 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. Conclusions 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.