P07.21.a a Phase I Trial to Determine the Maximum Tolerated Dose and Patient-Specific Dosimetry of Fractionated Intracavitary Radioimmunotherapy With Lutetium-177 Labeled 6a10 Fab Fragments in Patients With Glioblastoma - Preliminary Results From the First Patient Cohort

BACKGROUND Following maximal safe resection and standard adjuvant radio- and chemotherapy, approved maintenance therapies for glioblastoma are lacking. Intracavitary radioimmunotherapy (iRIT) injected into the resection cavity offers a promising strategy for improving local tumor. MATERIAL AND METHODS The NOA-22 study (NCT05533242) investigates the 6A10-Fab fragment targeting carboxyanhydrase XII, labelled with lutetium-177, in a prospective, single-armed, multicenter phase I study setting, following a modified 3 + 3-design. Malignant glioma (WHO grades 3 + 4) IV and III) after concomitant radio-chemotherapy and adjuvant standard chemotherapy with no or small residual disease are included. The injected activity is adapted to the volume of the resection cavity, resulting in a dose of 44Gy (cohort 1), 48Gy (cohort 2) and 52Gy (cohort 3). Primary study objective is to determine the maximum tolerated dose and safety of adjuvant radio-immunotherapy with lutetium-177 labeled 6A10-Fab fragments. RESULTS Three patients with glioblastoma concluded the first study cohort. No toxicities beyond grade 2 (CTCAE Version 5) were noted. One patient presented with a symptomatic increase in focal contrast enhancement and perifocal edema that decreased after a course of steroid treatment, consistent with therapy-associated changes. Dosimetry did not reveal absorbed doses above upper dose limits for organs at risk. All patients remain clinically stable and without tumor progression. CONCLUSION Intracavitary injection of Lutetium-177 labeled 6A10 Fab fragments appears to be feasible and safe. The study currently enrolls patients in a planned escalated dose scheme of 48 Gy cumulative dose in cohort 2.