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

doi:10.1016/j.lungcan.2006.05.020

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

Hematology/Oncology

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

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 (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/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 language	English (US)
Pages (from-to)	69-77
Number of pages	9
Journal	Lung Cancer
Volume	54
Issue number	1
DOIs	https://doi.org/10.1016/j.lungcan.2006.05.020
State	Published - Oct 2006

Keywords

Immunoconjugate
Lewis Y
Monoclonal antibody
Nsclc
Sgn-15
Targeted therapy

ASJC Scopus subject areas

Oncology
Pulmonary and Respiratory Medicine
Cancer Research

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10.1016/j.lungcan.2006.05.020

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Ross, H. J., Hart, L. L., Swanson, P. M., Rarick, M. U., Figlin, R. A., Jacobs, A. D., McCune, D. E., Rosenberg, A. H., Baron, A. D., Grove, L. E., Thorn, M. D., Miller, D. M., Drachman, J. G., & Rudin, C. M. (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, 54(1), 69-77. https://doi.org/10.1016/j.lungcan.2006.05.020

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

@article{b61b0d6e857b48718cec6a4c65345c10,

title = "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",

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.",

keywords = "Immunoconjugate, Lewis Y, Monoclonal antibody, Nsclc, Sgn-15, Targeted therapy",

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

note = "Funding Information: Sincere thanks are extended to Michael MacDonald, MD, Amy Sing, MD, Andrew Sandier, MD, J. Michael White, PhD, Jennie Lorenz, CCRA, Katie Herz, CRA, Brenda Fisher, RN, Esther Bit-Ivan, Livia Szeto, RN, Cara O{\textquoteright}Keefe, Joanne Jelliffe, Christine Baker, RN, Heather Houston, RN, Cheryl Elzinga, Inger Thompson, Carol Ford, RN, Diane Perry, RN, and all of the clinical trial site personnel for their assistance in conducting this trial. We are grateful to Stephanie Boyer for her invaluable assistance in preparing this manuscript. This study was sponsored by Seattle Genetics, Inc.",

year = "2006",

month = oct,

doi = "10.1016/j.lungcan.2006.05.020",

language = "English (US)",

volume = "54",

pages = "69--77",

journal = "Lung Cancer",

issn = "0169-5002",

publisher = "Elsevier Ireland Ltd",

number = "1",

}

TY - JOUR

T1 - 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

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.

N1 - Funding Information: Sincere thanks are extended to Michael MacDonald, MD, Amy Sing, MD, Andrew Sandier, MD, J. Michael White, PhD, Jennie Lorenz, CCRA, Katie Herz, CRA, Brenda Fisher, RN, Esther Bit-Ivan, Livia Szeto, RN, Cara O’Keefe, Joanne Jelliffe, Christine Baker, RN, Heather Houston, RN, Cheryl Elzinga, Inger Thompson, Carol Ford, RN, Diane Perry, RN, and all of the clinical trial site personnel for their assistance in conducting this trial. We are grateful to Stephanie Boyer for her invaluable assistance in preparing this manuscript. This study was sponsored by Seattle Genetics, Inc.

PY - 2006/10

Y1 - 2006/10

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.

AB - 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.

KW - Immunoconjugate

KW - Lewis Y

KW - Monoclonal antibody

KW - Nsclc

KW - Sgn-15

KW - Targeted therapy

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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

Abstract

Keywords

ASJC Scopus subject areas

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