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

Helen J. Ross, Lowell L. Hart, Paul M. Swanson, Mark U. Rarick, Robert A. Figlin, Andrew D. Jacobs, David E. McCune, Arthur H. Rosenberg, Ari D. Baron, Laurie E. Grove, Michael D. Thorn, Dennis M. Miller, Jonathan G. Drachman, Charles M. Rudin

Research output: Contribution to journalArticle

Abstract

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 (Ley) antigen, conjugated to doxorubicin. Ley is an attractive target since it is expressed by most NSCLC. SGN-15 was active against Ley-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 Ley, one or two prior chemotherapy regimens, and PS≤2 were randomized 2:1 to receive SGN-15 200mg/m2/week with docetaxel 35mg/m2/week (Arm A) or docetaxel 35mg/m2/week alone (Arm B) for 6 of 8 weeks. Intrapatient dose-escalation of SGN-15 to 350mg/m2 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.

Original languageEnglish (US)
Pages (from-to)69-77
Number of pages9
JournalLung Cancer
Volume54
Issue number1
DOIs
StatePublished - Oct 2006

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docetaxel
Immunoconjugates
Non-Small Cell Lung Carcinoma
Multicenter Studies
Safety
Survival
Quality of Life
Drug Therapy
Therapeutics
Doxorubicin
Appointments and Schedules
Research Design
Monoclonal Antibodies
Clinical Trials

Keywords

  • Immunoconjugate
  • Lewis Y
  • Monoclonal antibody
  • Nsclc
  • Sgn-15
  • Targeted therapy

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

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. / 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.

In: Lung Cancer, Vol. 54, No. 1, 10.2006, p. 69-77.

Research output: Contribution to journalArticle

Ross, HJ, Hart, LL, Swanson, PM, Rarick, MU, Figlin, RA, Jacobs, AD, McCune, DE, Rosenberg, AH, Baron, AD, Grove, LE, Thorn, MD, Miller, DM, Drachman, JG & Rudin, CM 2006, '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', Lung Cancer, vol. 54, no. 1, pp. 69-77. https://doi.org/10.1016/j.lungcan.2006.05.020
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. / 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. In: Lung Cancer. 2006 ; Vol. 54, No. 1. pp. 69-77.
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abstract = "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 (Ley) antigen, conjugated to doxorubicin. Ley is an attractive target since it is expressed by most NSCLC. SGN-15 was active against Ley-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 Ley, one or two prior chemotherapy regimens, and PS≤2 were randomized 2:1 to receive SGN-15 200mg/m2/week with docetaxel 35mg/m2/week (Arm A) or docetaxel 35mg/m2/week alone (Arm B) for 6 of 8 weeks. Intrapatient dose-escalation of SGN-15 to 350mg/m2 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.",
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AU - Ross, Helen J.

AU - Hart, Lowell L.

AU - Swanson, Paul M.

AU - Rarick, Mark U.

AU - Figlin, Robert A.

AU - Jacobs, Andrew D.

AU - McCune, David E.

AU - Rosenberg, Arthur H.

AU - Baron, Ari D.

AU - Grove, Laurie E.

AU - Thorn, Michael D.

AU - Miller, Dennis M.

AU - Drachman, Jonathan G.

AU - Rudin, Charles M.

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N2 - 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 (Ley) antigen, conjugated to doxorubicin. Ley is an attractive target since it is expressed by most NSCLC. SGN-15 was active against Ley-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 Ley, one or two prior chemotherapy regimens, and PS≤2 were randomized 2:1 to receive SGN-15 200mg/m2/week with docetaxel 35mg/m2/week (Arm A) or docetaxel 35mg/m2/week alone (Arm B) for 6 of 8 weeks. Intrapatient dose-escalation of SGN-15 to 350mg/m2 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.

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