Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
A Phase I and Biodistribution Study of Ifabotuzumab, a Humanized Agonistic EphA3-Targeted Antibody, in Patients with Recurrent Glioblastoma.
СтатьяКлиническое исследование I фазыМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Gan Hui K, Cher Lawrence, Inglis Po-Ling, Lwin Zarnie, Gunjur Ashray, Balasubramanian Adi, Schmidt Andrew, Wichmann Christian W, Guo Nancy, Lee Sze Ting, Thomas Paul, Scott Fiona E, Shard Chloe, Fluck Kate, Coombs Nicole, Palmer Jodie, Vail Mary E, Allen Stacey, Patil Ashwini, Pal Bhupinder, O'Keefe Graeme J, Gong Sylvia J, Ninatti Gaia, Day Bryan W, Gomez Guillermo A, Janes Peter W, Scott Andrew M
Аннотация
PURPOSE: To conduct a phase I and biodistribution study of the EphA3 antibody ifabotuzumab and zirconium-89-labeled ifabotuzumab (89Zr-ifabotuzumab) in patients with glioblastoma (GBM).
PATIENTS AND METHODS: This multisite study was conducted in adults with recurrent GBM whose tumors were measurable according to Response Assessment in Neuro-Oncology (RANO) criteria and whose Eastern Cooperative Oncology Group performance status was 0 to 1. Patients underwent a biodistribution study with PET scans with 89Zr-ifabotuzumab, followed by three infusions of ifabotuzumab at either 3.5 or 5.25 mg/kg before undergoing a second study with 89Zr-ifabotuzumab PET scans. Resected patient diagnostic tumor samples were collected for multiplex immunofluorescence and spatial transcriptomics analyses.
RESULTS: Twelve patients were recruited, of which six were treated with 3.5 mg/kg and six with 5.25 mg/kg of ifabotuzumab. 89Zr-ifabotuzumab and associated PET scanning were well tolerated, as was ifabotuzumab. There were no objective responses, but one patient had prolonged stable disease. In addition, two patients showed changes in peritumor edema that were suggestive of modulation of tumor vasculature. 89Zr-ifabotuzumab scans showed highly specific tumor uptake in all patients concordant with disease sites on MRI and PET imaging, without evidence of nonspecific binding. Spatial transcriptomics and immunofluorescence analyses of the patient's archival tissue specimens showed that EphA3 was expressed in the tumor microenvironment in all patients and tumor cells with different transcriptional states.
CONCLUSIONS: Targeting EphA3 with ifabotuzumab in patients with GBM is safe and attractive, showing chronologic stable expression across both tumor compartments (particularly in cells with a mesenchymal phenotype) and nontumor compartments (particularly the vascular compartment) with evidence of target modulation.
PATIENTS AND METHODS: This multisite study was conducted in adults with recurrent GBM whose tumors were measurable according to Response Assessment in Neuro-Oncology (RANO) criteria and whose Eastern Cooperative Oncology Group performance status was 0 to 1. Patients underwent a biodistribution study with PET scans with 89Zr-ifabotuzumab, followed by three infusions of ifabotuzumab at either 3.5 or 5.25 mg/kg before undergoing a second study with 89Zr-ifabotuzumab PET scans. Resected patient diagnostic tumor samples were collected for multiplex immunofluorescence and spatial transcriptomics analyses.
RESULTS: Twelve patients were recruited, of which six were treated with 3.5 mg/kg and six with 5.25 mg/kg of ifabotuzumab. 89Zr-ifabotuzumab and associated PET scanning were well tolerated, as was ifabotuzumab. There were no objective responses, but one patient had prolonged stable disease. In addition, two patients showed changes in peritumor edema that were suggestive of modulation of tumor vasculature. 89Zr-ifabotuzumab scans showed highly specific tumor uptake in all patients concordant with disease sites on MRI and PET imaging, without evidence of nonspecific binding. Spatial transcriptomics and immunofluorescence analyses of the patient's archival tissue specimens showed that EphA3 was expressed in the tumor microenvironment in all patients and tumor cells with different transcriptional states.
CONCLUSIONS: Targeting EphA3 with ifabotuzumab in patients with GBM is safe and attractive, showing chronologic stable expression across both tumor compartments (particularly in cells with a mesenchymal phenotype) and nontumor compartments (particularly the vascular compartment) with evidence of target modulation.