Promising Preliminary Results in Glioblastoma
The investigator-initiated Phase 1 trial (NCT05533242) is a prospective, single-arm, multicenter, dose-escalation study evaluating the safety, tolerability and maximum tolerated dose of ITM-31, as well as progression-free survival (PFS) and overall survival (OS) in patients with newly diagnosed glioblastoma, following surgical resection and standard radio-chemotherapy, with no or minimal residual disease. ITM-31 is designed as a maintenance therapy applied during a period of stability. The study enrolled ten patients across four clinical sites at German university hospitals in Münster, Würzburg, Essen, and Cologne.
ITM-31 is a Lutetium-177-labeled 6A10 Fab fragment targeting carbonic anhydrase XII (CA XII), a cell surface protein expressed in >90% of glioblastoma cases but absent in healthy brain tissue. It is administered via intracavitary injection directly into the post-surgical resection cavity, enabling targeted radiation of residual tumor cells, bypassing the blood–brain barrier.
“By delivering ITM-31 directly into the surgical resection cavity, our goal is to achieve high targeted radiation exposure at the site of residual disease, while minimizing systemic toxicity,” said Dr. Michael Müther, study investigator and neurosurgeon at the University Hospital Münster. “Given the disease’s high rate of recurrence, strategies that address residual tumor cells locally may play an important role in improving outcomes.”
From Laboratory Discovery to Clinical Application
“We have come a long way from validating our antibody in the first cell assays to bringing it into the clinic. It has been a wonderful experience to partner with the University of Münster and ITM for this first study, and we are hopeful that glioblastoma patients will finally benefit from it,” says Prof. Reinhard Zeidler, Group Leader at the Institute of Structural Biology, Molecular Targets and Therapeutics Center, Helmholtz Munich, who identified and developed the CA XII-targeting 6A10 antibody fragment used in ITM-31.
Study Findings Support Further Development
Patients with newly diagnosed glioblastoma received individualized total doses of ITM-31 in three fractions with an interval of 4 weeks between injections after completion of standard of care therapy. There were three dose-escalating cohorts.
Interim analyses showed a manageable safety profile across all cohorts. Adverse events were predominantly reversible and manageable with standard treatment. No Grade ≥3 haematological toxicities were observed, and dosimetry confirmed that radiation exposure remained below established safety thresholds for organs at risk.
Importantly, no patient has experienced disease progression since enrolment began in January 2024. The longest-followed patient has remained progression-free for up to 25 months, suggesting meaningful local tumour control.
“These preliminary results support the potential of intracavitary targeted radiotherapy with ITM-31 as a novel approach for patients with glioblastoma, where outcomes remain extremely poor following standard of care treatment,” said Dr. Celine Wilke, chief medical officer of ITM. “The safety profile and early signs of anti-tumor activity observed to date support continued clinical development.”
About the Program
Patients will continue to be followed for up to two years after initial treatment with ITM-31. Preliminary pilot data were published in EJNMMI Research (2023), demonstrating the feasibility and safety of intracavitary administration of [¹⁷⁷Lu]6A10-Fab fragments in patients with glioblastoma.
About Glioblastoma
Glioblastoma is the most common and aggressive primary malignant brain tumor in adults, accounting for nearly half of all gliomas and affecting more than 25,000 patients annually in Europe and over 100,000 worldwide. In the United States, approximately 12,000–14,000 new cases are diagnosed each year.
Despite standard treatment with surgery, radiation and chemotherapy, outcomes remain poor, with median overall survival of approximately 15–20 months. Recurrence mostly occurs around the original tumor site, underscoring the need for effective locoregional therapies. The blood-brain barrier further limits the impact of many systemic treatments, highlighting the need for novel therapeutic approaches.
