Phase I trial of murine monoclonal antibody L6 in breast, colon, ovarian, and lung cancer.
Murine monoclonal antibody (MAb) L6 binds to an antigen expressed on the surface of breast, colon, ovary, and nonsmall-cell lung cancer. This antibody effects antibody-dependent cellular cytotoxicity (ADCC) with human mononuclear cells and complement-dependent cytotoxicity (CDC) with human complement. Because of these activities, we conducted a phase I trial of MAb L6 in patients with advanced cancer. Nineteen patients whose tumors highly expressed antigen were selected for this trial. Eighteen were evaluable. MAb L6 was administered at dose levels ranging from 5 mg/m2/d to 400 mg/m2/d for 7 days and was well tolerated. The only side effects detected were fever and headaches at the highest dose levels. The serum half-life of L6 was directly related to dose and ranged from a mean of 7.7 hours at 5 mg/m2/d to 29.1 hours at 400 mg/m2/d. Peak serum concentrations ranged from 0.22 micrograms/mL to 362 micrograms/mL. Biopsies at the end of treatment showed L6 to localize well to tumor cells with apparent in vivo saturation occurring at dose levels above 100 mg/m2/d. Thirteen patients formed human antimouse antibodies (HAMA), some as early as day 13. One patient with recurrent breast cancer on the chest wall achieved a complete remission. The response was first noted at 5 weeks and a pathologic complete remission occurred at 14 weeks. Because of its favorable binding properties and the encouraging clinical effect observed, future evaluation of this MAb appears warranted.
Goodman
G E
GE
Swedish Hospital Tumor Institute, Seattle, WA 98104.
Hellström
I
I
Brodzinsky
L
L
Nicaise
C
C
Kulander
B
B
Hummel
D
D
Hellström
K E
KE
D000328:Adult; D000368:Aged; D000818:Animals; D000906:Antibodies / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000276:immunology; D002986:Clinical Trials as Topic; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D051379:Mice / Q000276:immunology; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm