A Phase 1 Study of EMD 525797 (DI17E6), A Humanized Monoclonal Antibody to Human AV Integrins, in CRPC with Bone Metastases After Chemotherapy
| Autor: | Michael Laniado, Axel Heidenreich, M. Wirth, Jürgen E. Gschwend, Stefan Zastrow, Wolfgang Uhl, Michael Zühlsdorf, Thierry Gil, Heinrich Lannert, Joachim J. Gerloff |
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| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Chemotherapy business.industry medicine.medical_treatment Peripheral edema Hematology medicine.disease Rash Primary tumor Gastroenterology Prostate-specific antigen Oncology Tolerability Internal medicine medicine medicine.symptom business Adverse effect Progressive disease |
| Zdroj: | Annals of Oncology. 23:xi21 |
| ISSN: | 0923-7534 |
| DOI: | 10.1016/s0923-7534(20)31972-4 |
| Popis: | Background EMD 525797 is a humanized monoclonal IgG2 antibody specifically targeting av integrins involved in tumor progression. Methods The safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of EMD 525797 were assessed in metastatic castrate-resistant prostate cancer (mCRPC) patients. 24 patients (43-80 years) were treated with IV infusions of 250, 500, 1000, or 1500 mg EMD 525797 given over 1 h and received 3 doses (weeks 1, 3, and 5) before response assessment at the end of week 6. Patients without progressive disease could receive further doses every 2 weeks. Dose-limiting toxic effects (DLTs) were assessed over the first 6 weeks and safety was monitored until 4 weeks after the last administration of EMD 525797. Results Final analysis showed that 13 of 24 patients had a longer exposure time than expected(≥84 days): 7 patients had exposure times ≥126 days, 3 patients ≥280 days and 1 patient received EMD 525797 for 534 days. All patients experienced adverse events (AEs), and in 11 patients AEs were considered related to EMD 525797. 4 patients had generalized pruritus, erythema, or rash and 3 patients experienced fatigue, mucosal inflammation, or peripheral edema, but no patient had administration site reactions. Changes in clinical lab values were consistent with basic disease. No DLTs occurred. EMD 525797 showed a dose-dependent, nonlinear PK profile in line with a target-mediated drug disposition. Two patients of the 500 mg cohort had a marked decrease in prostate specific antigen. One of them also had primary tumor shrinkage and normalization of lymph node size. These patients had long-term anti-integrin treatment (297 and 534 days, respectively). Both patients showed additional pain relief. |
| Databáze: | OpenAIRE |
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