ESMO open · 2026
First-in-human phase I study of hypoxia-targeting 64Cu-ATSM radioligand therapy in patients with malignant brain tumors (STAR-64).
СтатьяКлиническое исследование I фазыНазвание и аннотация: Перевод в очереди
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Kurihara H, Narita Y, Ito K, Sato H, Miyakita Y, Takahashi M, Ohno M, Yanagisawa S, Okita N T, Sadachi R, Machida R, Tateishi K, Yoshii Y, Waki A, Hashimoto H, Suzuki H, Zhang M-R, Kawamura K, Honda N, Yoshimoto M, Matsumoto H
Аннотация
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 months for a patient with glioblastoma (99 MBq/kg). The 1-year and median overall survival (OS) were 76.6% and 29.4 months, respectively, in all 18 patients; 12 patients (66.7%) were long-term survivors of ≥12 months. Among nine patients with glioblastoma, the 1-year and median OS were 64.8% and 17.7 months, respectively, suggesting favorable preliminary outcomes compared with historical references. Pharmacokinetic and dosimetry analyses revealed a clinically favorable distribution and organ radiation doses of 64Cu-ATSM, supporting the selected dosing regimen and schedule.
CONCLUSIONS: 64Cu-ATSM therapy was well tolerated and demonstrated preliminary efficacy in patients with recurrent malignant brain tumors, particularly glioblastoma, supporting further evaluation in an ongoing phase III study (STEP-64, jRCT2031240090).
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 months for a patient with glioblastoma (99 MBq/kg). The 1-year and median overall survival (OS) were 76.6% and 29.4 months, respectively, in all 18 patients; 12 patients (66.7%) were long-term survivors of ≥12 months. Among nine patients with glioblastoma, the 1-year and median OS were 64.8% and 17.7 months, respectively, suggesting favorable preliminary outcomes compared with historical references. Pharmacokinetic and dosimetry analyses revealed a clinically favorable distribution and organ radiation doses of 64Cu-ATSM, supporting the selected dosing regimen and schedule.
CONCLUSIONS: 64Cu-ATSM therapy was well tolerated and demonstrated preliminary efficacy in patients with recurrent malignant brain tumors, particularly glioblastoma, supporting further evaluation in an ongoing phase III study (STEP-64, jRCT2031240090).