Phase I Trial of Weekly Tigatuzumab, an Agonistic Humanized Monoclonal Antibody Targeting Death Receptor 5 (DR5)
| Autor: | Slawomir Wojtowicz-Praga, Jatin J. Shah, Andres Forero-Torres, Feng Roger Luo, T. E. Wood, Catherine Copigneaux, I. Percent, James Posey, Mansoor N. Saleh, Ronda Carlisle |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Cancer Research Lymphoma medicine.drug_class medicine.medical_treatment Apoptosis Pharmacology Monoclonal antibody Antibodies Monoclonal Humanized chemistry.chemical_compound Pharmacokinetics In vivo medicine Humans Radiology Nuclear Medicine and imaging Tigatuzumab Research Articles Aged Aged 80 and over biology Dose-Response Relationship Drug business.industry Immunogenicity Carcinoma Antibodies Monoclonal General Medicine Immunotherapy Middle Aged Receptors TNF-Related Apoptosis-Inducing Ligand Oncology chemistry Monoclonal biology.protein Female Antibody business |
| Popis: | TRA-8 is a murine agonist monoclonal antibody to death receptor 5 (DR5), which is able to trigger apoptosis in DR5 positive human tumor cells without the aid of crosslinking. It has demonstrated cytotoxicity in vitro and in vivo antitumor efficacy to a wide range of solid tumors in murine xenograft models. Tigatuzumab is a humanized IgG1 monoclonal antibody derived from TRA-8.A phase I trial of tigatuzumab in patients with relapsed/refractory carcinomas (n = 16) or lymphoma (n = 1) was designed to determine the maximal tolerated dose (MTD), pharmacokinetics, immunogenicity, and safety. Three to six (3-6) patients were enrolled in successive escalating cohorts at doses ranging from 1 to 8 mg/kg weekly.Seventeen (17) patients enrolled, 9 in the 1-, 2-, and 4-mg/kg dose cohorts (3 in each cohort) and 8 in the 8-mg/kg dose cohort. Tigatuzumab was well tolerated with no DLTs observed, and the MTD was not reached. There were no study-drug-related grade 3 or 4, renal, hepatic, or hematologic toxicities. Plasma half-life was 6-10 days, and no anti-tigatuzumab responses were detected. Seven (7) patients had stable disease, with the duration of response ranging from 81 to 798 days.Tigatuzumab is well tolerated, and the MTD was not reached. The high number of patients with stable disease suggests antitumor activity. |
| Databáze: | OpenAIRE |
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