Phase I trial of the chimeric anti-GD2 monoclonal antibody ch14.18 in patients with malignant melanoma

PURPOSE To evaluate the toxicity, immunogenicity, and pharmacokinetics of a human-mouse chimeric monoclonal antibody (mAb) ch 14.18 directed against disialoganglioside (GD2) and to obtain preliminary information on its clinical efficacy, we conducted a phase I trial in 10 patients with refractory neuroblastoma and one patient with osteosarcoma. PATIENTS AND METHODS Eleven patients were entered onto this phase I trial. They received 20 courses of mAb ch 14.18 at dose levels of 10, 20, 50, 100, and 200 mg/m2. Dose escalation was performed in cohorts of three patients; intrapatient dose escalation was also permitted. RESULTS The most prevalent toxicities were pain, tachycardia, hypertension, fever, and urticaria. Most of these toxicities were dose-dependent and rarely noted at dosages of 20 mg/m2 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 (MRs) and one stable disease (SD) among 10 assessable patients. Biologic activity of ch 14.18 in vivo was shown by binding of ch 14.18 to tumor cells and complement-dependent cytotoxicity of posttreatment sera against tumor target cells. An anti-ch 14.18 immune response was detectable in seven of 10 patients studied. CONCLUSION In summary, with the dose schedule used, ch 14.18 appears to be clinically safe and effective, and repeated mAb administration was not associated with increased toxicities. Further clinical trials of mAb ch 14.18 in patients with neuroblastoma are warranted.

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Abstract 748: Phase I trial of fractionated-dose177Lutetium radiolabeled anti-prostate-specific membrane antigen monoclonal antibody J591 (177Lu-J591) in patients with metastatic castration-resistant prostate cancer (metCRPC)

10.1158/1538-7445.am2012-748 ◽

2012 ◽

Cited By ~ 1

Author(s):

Scott T. Tagawa ◽

Shankar Vallabhajosula ◽

Naveed H. Akhtar ◽

Joseph Osborne ◽

Himisha Beltran ◽

...

Keyword(s):

Prostate Cancer ◽

Monoclonal Antibody ◽

Phase I ◽

Phase I Trial ◽

Prostate Specific Membrane Antigen ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Specific Membrane

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High-dose therapy with iodine-131-labeled monoclonal antibody CC49 in patients with gastrointestinal cancers: a phase I trial.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.4.1518 ◽

1997 ◽

Vol 15 (4) ◽

pp. 1518-1528 ◽

Cited By ~ 45

Author(s):

M Tempero ◽

P Leichner ◽

G Dalrymple ◽

K Harrison ◽

S Augustine ◽

...

Keyword(s):

Stem Cells ◽

Monoclonal Antibody ◽

Radiation Dose ◽

Phase I ◽

Hematopoietic Stem Cells ◽

Phase I Trial ◽

Gastrointestinal Cancers ◽

Hematopoietic Stem ◽

Iodine 131 ◽

Absorbed Radiation Dose

PURPOSE A phase I trial that evaluated for extrahematopoietic toxicity was conducted with iodine-131 (131I) labeled monoclonal antibody (MAb) CC49. Correlative studies included pharmacokinetic and biodistribution analyses, estimates of absorbed radiation dose, and measurement of human antimonoclonal antibodies (HAMA). PATIENTS AND METHODS After collection and cryopreservation of hematopoietic stem cells, 15 patients with gastrointestinal cancers were administered a tracer dose of 131I-MAb CC49. Within 5 to 6 days, 14 patients (two to three per activity level) underwent a single treatment with 131I-MAb CC49 (50, 100, 150, 200, 250, and 300 mCi/m2). Biodistribution was determined using planar and single photon emission computer tomographic (SPECT) imaging. Pharmacokinetic studies were performed by measuring radioactivity in serial blood samples. In some patients, biopsies of metastases and related normal tissues were obtained for radioactivity measurements. Radiation dosimetry estimates were calculated using available biodistribution, pharmacokinetic, and tissue biopsy data. Toxicity was evaluated using the National Cancer Institute (NCI) Common Toxicity Criteria. RESULTS No dose-limiting extrahematopoietic toxicity was identified. Twelve patients experienced grade IV myelosuppression and met criteria for infusion of hematopoietic stem cells. Radioimmunolocalization was excellent. The T1/2 for 131I-MAb CC49 after diagnostic and therapeutic administration was 39.7 +/- 10.4 and 46.1 +/- 10.6 hours, respectively. The percent injected dose per killigram of tumor ranged from 0.2 to 2.1. Absorbed radiation dose in metastatic tumor sites ranged from 630 to 3300 cGy. CONCLUSION Although extrahematopoietic dose-limiting toxicity was neither observed or predicted, suboptimal absorbed dose estimates suggested that further escalation of 131I-MAb CC49 would not be useful. Future studies should focus on the use of radionuclides with high energy beta emissions, such as yttrium 90, and on strategies to optimize access of antibody to target antigens.

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