Safety and tolerability of asunercept plus standard radiotherapy/temozolomide in Asian patients with newly-diagnosed glioblastoma: a phase I study

• Published in: Scientific reports Vol. 11; no. 1; pp. 24067 - 9
• Main Authors: Wei, Kuo-Chen, Hsu, Peng-Wei, Tsai, Hong-Chieh, Lin, Ya-Jui, Chen, Ko-Ting, Toh, Cheng-Hong, Huang, Hui-Lin, Jung, Shih-Ming, Tseng, Chen-Kan, Ke, Yu-Xiong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.12.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/154; 631/67; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Asians; Biomarkers; Brain cancer; Brain Neoplasms - diagnosis; Brain Neoplasms - etiology; Brain Neoplasms - mortality; Brain Neoplasms - therapy; Combined Modality Therapy; Disease Management; Drug Monitoring; fas Receptor - administration & dosage; Fusion protein; Glioblastoma; Glioblastoma - diagnosis; Glioblastoma - etiology; Glioblastoma - mortality; Glioblastoma - therapy; Humanities and Social Sciences; Humans; Immunoglobulin G - administration & dosage; Kaplan-Meier Estimate; multidisciplinary; Patients; Pharmacokinetics; Prognosis; Radiation therapy; Radiotherapy; Recombinant Fusion Proteins - administration & dosage; Safety; Science; Science (multidisciplinary); Temozolomide; Temozolomide - administration & dosage; Treatment Outcome
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-02527-1

Asunercept (company code APG101 [Apogenix AG]; company code CAN008 [CANbridge Pharmaceuticals]) is a novel glycosylated fusion protein that has shown promising effectiveness in glioblastoma. This Phase I study was initiated to evaluate the tolerability and safety of asunercept in combination with standard radiotherapy and temozolomide (RT/TMZ) in Asian patients with newly diagnosed glioblastoma. This was the Phase I portion of a Phase I/II open label, multicenter trial of asunercept plus standard RT/TMZ. Adults with newly-diagnosed glioblastoma received surgical resection followed by standard RT/TMZ plus asunercept 200 mg/week (Cohort 1) or 400 mg/week (Cohort 2) by 30-min IV infusion. The primary endpoint was the safety and tolerability of asunercept during concurrent asunercept and RT/TMZ; dose-limiting toxicities were observed for each dose. Secondary endpoints included pharmacokinetics (PK) and 6-month progression-free survival (PFS6). All patients (Cohort 1, n = 3; Cohort 2, n = 7) completed ≥ 7 weeks of asunercept treatment. No DLTs were experienced. Only one possibly treatment-related treatment emergent adverse event (TEAE), Grade 1 gingival swelling, was observed. No Grade > 3 TEAEs were reported and no TEAE led to treatment discontinuation. Systemic asunercept exposure increased proportionally with dose and showed low inter-patient variability. The PFS6 rate was 33.3% and 57.1% for patients in Cohort 1 and 2, respectively. Patients in Cohort 2 maintained a PFS rate of 57.1% at Month 12. Adding asunercept to standard RT/TMZ was safe and well tolerated in patients with newly-diagnosed glioblastoma and 400 mg/week resulted in encouraging efficacy. Trial registration NCT02853565, August 3, 2016.