A new Phase 1 clinical trial, CITADEL-123, is offering hope to patients with recurrent glioblastoma, an aggressive form of brain cancer. The trial, led by Dr. Paul Mulholland at University College London Hospital (UCLH), utilizes a novel radiopharmaceutical approach to target and destroy tumor cells while sparing healthy tissue. The first patient treated in the trial has shown a 50% reduction in tumor size, marking a promising early result.
Targeted Radiotherapy with ATT001
The CITADEL-123 trial investigates ATT001, an Iodine-123 labelled PARP inhibitor developed by Ariceum Therapeutics. The drug is administered directly into the tumor via an Ommaya reservoir, a small device implanted under the scalp following surgical resection of the tumor. This allows for targeted delivery of small amounts of radioactivity to the cancer cells.
ATT001 delivers its radioisotope payload, Iodine-123, in a highly targeted way to cancer cells expressing PARP, an enzyme they use to repair themselves. This radioisotope emits low energy Auger electrons, which deposit their energy over short distances, making them particularly useful for causing lethal damage to cancer cells while sparing healthy tissue.
Trial Design and Patient Selection
Patients with recurrent glioblastoma who have undergone standard treatment, including surgery, radiotherapy, and chemotherapy, are eligible for the trial. The trial involves surgical resection of the tumor followed by implantation of the Ommaya reservoir. Approximately 14 days post-surgery, patients receive weekly injections of ATT001 for 4 to 6 weeks.
The trial is designed as a dose escalation study, with plans to expand into cohorts evaluating the drug in combination with other therapies. The ultimate goal is to assess the safety and efficacy of ATT001 and potentially move into trials for primary glioblastoma.
Expert Perspectives
Dr. Paul Mulholland emphasized the collaborative effort behind the trial, stating, "We have been working with Ariceum Therapeutics for some years to develop this study... Potentially this is a very powerful approach and I’m already extremely happy with the results from the first patient."
Dr. Austin Smith from Ariceum Therapeutics added, "The CITADEL-123 study will allow us to demonstrate the safety and initial efficacy of ATT001 as a potential treatment option to address the high unmet medical need of patients with recurrent glioblastoma."
Significance and Future Directions
Glioblastoma is a devastating disease with limited treatment options, especially in recurrent cases. The CITADEL-123 trial represents a significant step forward in exploring novel therapeutic approaches. The targeted nature of ATT001, combined with the precision of Auger electron therapy, offers the potential to improve outcomes while minimizing side effects.
The trial is currently open at UCLH, with plans to expand to other sites. Further research will focus on optimizing dosing regimens, exploring combination therapies, and ultimately, evaluating the potential of ATT001 in primary glioblastoma.
