PHASE-I TRIAL OF A HUMAN-MOUSE CHIMERIC ANTI-DISIALOGANGLIOSIDE MONOCLONAL-ANTIBODY CH14.18 IN PATIENTS WITH REFRACTORY NEUROBLASTOMA AND OSTEOSARCOMA

purpose: To evaluate the toxicity, immunogenicity, and pharmacokinetic s of a human-mouse chimeric monoclonal antibody (mAb) ch14.18 directed against disialoganglioside (GD2) and to obtain preliminary informatio n on its clinical efficacy, we conducted a phase I trial in 10 patient s with refractory neuroblastoma and one patient with osteosarcoma. Pat ients and Methods: Eleven patients were entered onto this phase I tria l. They received 20 courses of mAb ch14.18 at dose levels of 10, 20, 5 0, 100, and 200 mg/m(2), Dose escalation was performed in cohorts of t hree patients; intrapatient dose escalation was also permitted. Result s: The most prevalent toxicities were pain, tachycardia, hypertension, fever, and urticaria. Most of these toxicities were dose-dependent an d rarely noted at dosages of 20 mg/m(2) and less. Although the maximum tolerated dose was not reached in this study, clinical responses were observed. These included one partial (PR) and four mixed responses (M Rs) and one stable disease (SD) among 10 assessable patients. Biologic activity of ch14.18 in vivo was shown by binding of ch14.18 to tumor cells and complement-dependent cytotoxicity of posttreatment sera agai nst tumor target cells. An anti-ch14.18 immune response was detectable in seven of 10 patients studied. Conclusion: In summary, with the dos e schedule used, ch14.18 appears to be clinically safe and effective, and repeated mAb administration was not associated with increased toxi cities. Further clinical trials of mAb ch14.18 in patients with neurob lastoma are warranted. (C) 1998 by American Society of Clinical Oncolo gy.