DDEL-09. FRACTIONATED INTRACAVITARY RADIOIMMUNOTHERAPY WITH LU-177 LABELED 6A10 FAB FRAGMENTS IN PATIENTS WITH GLIOBLASTOMA. (14th November 2022)

• Record Type: Journal Article
• Authors: Müther, Michael; Roll, Wolfgang; Böning, Guido; Delker, Astrid; Zeidler, Reinhard; Gildehaus, Franz Josef; Stegger, Lars; Schäfers, Michael; Reulen, Hans-Jürgen; Stummer, Walter
• Is Part Of: Neuro-oncology. Volume 24(2022)Supplement 7
• Page Start: vii95
• Page End: vii96
• Publication Date: 2022-11-14
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noac209.355
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Background: Radio-immunotherapy (RIT) with Lu- 177 labeled 6A10-Fab fragments, targeting tumor-associated carbonic anhydrase XII (CA12) and applied directly into the resection cavity, offers a promising strategy to address hibernating tumor burden after resection and completion of adjuvant treatment for glioblastoma. We report on the first in human applications. METHODS: Three patients underwent microsurgical resection of glioblastoma. After completion of adjuvant radio- and chemotherapy, RIT was offered in a compassionate use setting. After implantation of an injection reservoir into the tumor cavity, three consecutive doses of Lu-177 labeled 6A10 Fab fragments were administered over three months, corresponding to 25% - 50% - 25% of the total activity. The injected dose was adapted to the size of the resection cavity. Dosimetry was performed with planar whole-body scintigraphy and SPECT/CT 12h, 24h, 48h, 76h and 5-7 days after injection. RESULTS: Patient 1 (IDH1-Mutation) received three doses of RIT (total of 592 MBq) with stable disease 12 months after therapy and 26 months after initial diagnosis. Patient 2(IDH-Wildtype) had histologically proven tumor progression after the second cycle (total of 526 MBq). Patient 3 (IDH-Wildtype) has so far received one cycle of RIT (327 MBq of a planned total of 1300 MBq). No toxicity according to CTCAE version 6.0 or other adverse events related to RIT were observed. Dosimetry did not reveal absorbed doses above the upper dose limits for organs at risk. Conclusions: Intracavitary radioimmunotherapy with Lu-177 labeled 6A10-Fab fragments appears to be a safe maintenance therapy for glioblastoma patients, albeit only assessed in three compassionate use situations far. A multicenter confirmatory phase-I-trial will be was initiated in May 2022 (EudraCT-No: 2015-004417-25) to determine the maximum tolerated dose and safety of adjuvant RIT with Lu-177 labeled 6A10-Fab fragments.