A phase II clinical study of 13-deoxy, 5-iminodoxorubicin (GPX-150) with metastatic and unresectable soft tissue sarcoma

Cancer Med. 2019 Jun;8(6):2994-3003. doi: 10.1002/cam4.2136. Epub 2019 Apr 23.


Background: 13-Deoxy, 5-iminodoxorubicin (GPX-150) is a doxorubicin (DOX) analog synthesized to reduce the formation of reactive oxygen species and the cardiotoxic metabolite, doxorubiciniol, the two pathways that are linked to the irreversible, cumulative dose-dependent cardiotoxicity of DOX. In a preclinical chronic models and a phase I clinical study of GPX-150, no irreversible, cumulative dose-dependent cardiotoxicity was demonstrated. Recent studies suggest that DOX cardiotoxicity may be mediated, at least in part, by the poisoning of topoisomerase IIβ.

Patients and methods: An open-label, single-arm phase II clinical study in metastatic and unresectable soft tissue sarcoma (STS) patients was initiated to further evaluate the efficacy and safety of GPX-150, including cardiac function, specifically left ventricular ejection fraction (LVEF).

Results: GPX-150 was administered at 265 mg/m2 every 3 weeks for up to 16 doses with prophylactic G-CSF until progression, death, or patient withdrawal from the study. GPX-150 exhibited efficacy assessed as progression-free survival (PFS) rates of 38% and 12% at 6 and 12 months and an overall survival rate of 74% and 45% at 6 and 12 months. GPX-150-treated patients did not develop any evidence of irreversible, cumulative dose-dependent chronic cardiotoxicity. Toxicities included grade 3 anemia, neutropenia, and one grade 4 leukopenia. Correlative analysis demonstrated that GPX-150 was more selective than DOX for the inhibition of topoisomerase IIα over IIβ in vitro.

Conclusion: These results suggest future studies are warranted to further evaluate the clinical efficacy of GPX-150 in STS, perhaps at doses higher than 265 mg/m2 .

Keywords: GPX-150; anthracyclines; cardiotoxicity; doxorubicin; phase II; soft tissue sarcoma.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Sarcoma / drug therapy*
  • Sarcoma / mortality
  • Soft Tissue Neoplasms / drug therapy*
  • Soft Tissue Neoplasms / mortality


  • Doxorubicin
  • 5-imino-13-deoxydoxorubicin