Phase I clinical comparative study of monoclonal antibody KS1/4 and KS1/4-methotrexate immunconjugate in patients with non-small cell lung carcinoma.
A Phase Ia clinical trial was undertaken to evaluate and compare murine monoclonal antibody KS1/4 and KS1/4-methotrexate immunoconjugate in patients with Stage IIIB or IV non-small cell carcinoma of the lung. Six patients received KS1/4 alone and five patients received KS1/4-methotrexate conjugate. The maximal total dose received per patient in both groups was 1661 mg. Mild to moderate side effects in both groups included fever, chills, anorexia, nausea, vomiting, diarrhea, anemia, and brief transaminasemia. One patient who received antibody alone had an apparent acute immune complex-mediated reaction. Ten of 11 patients had a human anti-mouse response. Posttreatment carcinoma biopsies revealed binding of monoclonal antibody KS1/4 and deposition of C3d and C4c complement fragments. Monoclonal antibody binding and complement deposition correlated with increasing doses of infused antibody. There was one possible clinical response.
Elias
D J
DJ
Department of Molecular and Experimental Medicine, Scripps Clinic and Research Foundation, La Jolla, California 92037.
Hirschowitz
L
L
Kline
L E
LE
Kroener
J F
JF
Dillman
R O
RO
Walker
L E
LE
Robb
J A
JA
Timms
R M
RM
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000032:analysis / Q000276:immunology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000032:analysis / Q000097:blood / Q000188:drug therapy*; D015815:Cell Adhesion Molecules; D002986:Clinical Trials as Topic; D004341:Drug Evaluation; D000071858:Epithelial Cell Adhesion Molecule; D006801:Humans; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000009:adverse effects / Q000032:analysis / Q000627:therapeutic use*; D000922:Immunotoxins / Q000009:adverse effects / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000032:analysis / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D007074:Immunoglobulin G; D000922:Immunotoxins; D008727:Methotrexate