First-in-Human, Open-label, Single-Arm Phase I Study of [211At] meta-Astatobenzylguanidine in Patients with Pheochromocytoma or Paraganglioma
Abstract
Purpose: The efficacy of current therapeutic options for pheochromocytomas and paragangliomas, such as 131I-meta-iodobenzylguanidine (131I-MIBG), is limited owing to low complete response rates and a requirement for prolonged radiation isolation. In this regard, α-emitting meta-astatobenzylguanidine labeled with astatine-211 (211At-MABG) has demonstrated encouraging nonclinical results in mice, yet its clinical potential remains unclear. This first-in-human, open-label, single-arm phase I clinical study aimed to evaluate the safety, pharmacokinetics (PK), and recommended dose of 211At-MABG.
Patients and methods: Ten participants with unresectable or metastatic treatment-refractory pheochromocytomas or paragangliomas and confirmed 123I-MIBG uptake were enrolled between June 2022 and May 2025. Using a 3 + 3 dose-escalation design (0.65, 1.3, and 2.1 MBq/kg), they received a single intravenous dose of 211At-MABG.
Results: No dose-limiting toxicities were observed during the 6-week evaluation period. The cumulative urinary excretion of 211At-MABG reached 65% within 72 hours, indicating rapid systemic clearance. One, 7, and 2 patients exhibited a partial response (PR), stable disease, and progressive disease, respectively, during a maximum follow-up period of 12 weeks.
Conclusions: A single dose of 211At-MABG at 2.1 MBq/kg was well tolerated and demonstrated predictable PK. Preliminary antitumor activity was observed, including 1 PR during the 12-week period. These findings…
How strong is the evidence?
Evidence Hub reads this as a clinical trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 7 participants or records.
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