First-in-human phase I study of hypoxia-targeting 64Cu-ATSM radioligand therapy in patients with malignant brain tumors (STAR-64)
Abstract
BACKGROUND: Hypoxic microenvironments throughout tumors contribute to proliferation and resistance to chemoradiotherapy. Copper-64 diacetyl-bis(N4-methylthiosemicarbazone) (64Cu-ATSM) is a first-in-class drug enabling hypoxia-targeting radioligand therapy with β- particles and high-linear energy transfer Auger electrons, originally employed for positron emission tomography imaging. We report the first-in-human study of 64Cu-ATSM therapy in patients with recurrent brain tumors.
PATIENTS AND METHODS: This phase I dose-escalation trial (STAR-64, jRCT2091220362) evaluated intravenous 64Cu-ATSM administered four times at 30, 60, 99, or 150 MBq/kg weekly in patients with recurrent malignant brain tumors, using the 3 + 3 design. Primary objectives were to assess dose-limiting toxicities (DLTs) and determine the maximum tolerated dose (MTD). Secondary objectives included efficacy, pharmacokinetics, and organ dosimetry.
RESULTS: Eighteen patients received 64Cu-ATSM: grade 3 glioma (anaplastic astrocytoma and anaplastic oligodendroglioma) 27.8%, grade 4 glioma (glioblastoma) 50%, malignant meningioma 11.1%, and metastatic brain tumors 11.1%. DLTs, consisting only of grade 3 lymphopenia, were observed in four patients: one at 60 MBq/kg, one at 99 MBq/kg, and two at 150 MBq/kg. The MTD was established as 99 MBq/kg. Two patients had a radiographic complete response by RECIST v1.1 with long-term survival: ≥45 months for a patient with anaplastic oligodendroglioma (60 MBq/kg) and ≥23…
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: 18 participants or records.
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