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

Sci Rep. 2021 Dec 15;11(1):24067. doi: 10.1038/s41598-021-02527-1.

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.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asian People
  • Biomarkers
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / etiology
  • Brain Neoplasms / mortality
  • Brain Neoplasms / therapy*
  • Combined Modality Therapy
  • Disease Management
  • Drug Monitoring
  • Glioblastoma / diagnosis
  • Glioblastoma / etiology
  • Glioblastoma / mortality
  • Glioblastoma / 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

Substances

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

Associated data

  • ClinicalTrials.gov/NCT02853565