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

Abstract

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.

• Authors: Kuo-Chen Wei, Peng-Wei Hsu, Hong-Chieh Tsai, Ya-Jui Lin, Ko-Ting Chen, Cheng-Hong Toh, Hui-Lin Huang, Shih-Ming Jung, Chen-Kan Tseng, Yu-Xiong Ke
• Journal: Scientific reports (Sci Rep) Vol. 11 Issue 1 Pg. 24067 (12 15 2021) ISSN: 2045-2322 [Electronic] England
• PMID: 34911992 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• Biomarkers
• Immunoglobulin G
• Recombinant Fusion Proteins
• fas Receptor
• APG101
• Temozolomide

Topics

• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Asian People
• Biomarkers
• Brain Neoplasms (diagnosis, etiology, mortality, therapy)
• Combined Modality Therapy
• Disease Management
• Drug Monitoring
• Glioblastoma (diagnosis, etiology, mortality, therapy)
• Humans
• Immunoglobulin G (administration & dosage)
• Kaplan-Meier Estimate
• Prognosis
• Radiotherapy
• Recombinant Fusion Proteins (administration & dosage)
• Temozolomide (administration & dosage)
• Treatment Outcome
• fas Receptor (administration & dosage)