Outcomes of the miltuximab first in human trial and proposed study design for a phase I trial 89Zr/177Lu theranostic trial
| Autor: | Kevin Ho Shon, Pirooz Poursoultan, Tiffany R. Mackay, Howard Gurney, Dale L. Bailey, Brad Walsh, David Gillatt, Dhanusha Sabanathan, Douglas Campbell, Paul Roach, Marko Trifunovic |
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| Rok vydání: | 2019 |
| Předmět: |
Chimeric antibody
Oncology Cancer Research medicine.medical_specialty business.industry medicine.medical_treatment First in human medicine.disease 03 medical and health sciences Prostate cancer 0302 clinical medicine 030220 oncology & carcinogenesis Internal medicine Radioimmunotherapy medicine business 030215 immunology |
| Zdroj: | Journal of Clinical Oncology. 37:261-261 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 261 Background: Miltuximab is a chimeric antibody targeting Glypican-1 which is overexpressed in prostate cancer. Miltuximab has shown promising safety and efficacy in radioimmunotherapy models of prostate cancer. Methods: Metastatic patients (prostate, pancreatic and bladder) were dosed with unlabelled Miltuximabfollowed by the infusion of 1 mg/250MBq 67Ga-Miltuximab. Patients underwent whole body gamma and SPECT/CT scans up to 144 hours post-infusion. Standard of care imaging was performed at least 14 days before and after participation. Safety was evaluated by an external monitoring committee. Total organ exposure was determined by dosimetry of whole-body gamma scans. Antibody pharmacokinetics were also determined. Results: 12 patients were enrolled into the trial. Miltuximabwas well tolerated and did not elicit any drug-related adverse reactions. Liver and spleen uptake of 67Ga-Miltuximabwas observed from 30 min to 72 hours post dose. Pre-infusion of unlabelled Miltuximab resulted in reduced liver accumulation and increased distribution in the rest of the body. Miltuximab targeting to sites of active progressive disease was observed in certain prostate cancer patients who had failed enzalutamide treatment. Dosimetry analysis combined with antibody pharmacokinetic data was used to establish safe dose limits for a Phase 1 study. Conclusions: This study is the first in human for Miltuximaband demonstrates its potential for further clinical evaluation as a theranostic in prostate cancers and formed the basis for a Phase I imaging and therapy study planned for 2019. This study will use 89Zr-labelled Miltuximab to screen eligible patients and confirm tumour localisation, followed by treatment with 177Lu-labelled Miltuximab. Clinical trial information: ACTRN12616000787482. |
| Databáze: | OpenAIRE |
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