Phase 1b Study of IGF-Methotrexate Conjugate in the Treatment of High-grade Myelodysplastic Syndromes

Anticancer Res. 2020 Jul;40(7):3883-3888. doi: 10.21873/anticanres.14378.

Abstract

Background/aim: The insulin-like growth factor type 1 receptor (IGF-1R) is overexpressed in myelodysplastic syndrome (MDS) cells, and 765IGF-Methotrexate (IGF-MTX) is a conjugate of methotrexate and a variant of insulin-like growth factor-1 (IGF-1) designed to selectively target cancer cells through binding to IGF-1R. The aim of this study was to determine whether IGF-MTX would be effective to treat MDS.

Patients and methods: In this phase I clinical trial, two patients with high grade MDS or oligoblastic acute myeloid leukemia (O-AML) that had failed standard therapy were treated with IGF-MTX.

Results: No dose-limiting toxicity was observed. Both patients had stable or improved cell counts and CD34+ myelodysplastic cell counts and exceeded their life expectancy (both alive at 1.9 years despite a life expectancy of less than 6 months). Bone marrow blast counts decreased from 22% to 5% in one patient, and from 17% to 16% in the other.

Conclusion: In conclusion, IGF-MTX at 0.20 μM equivalents per kg was well tolerated, caused no cytopenia, and produced stable disease and extension of life.

Keywords: IGF-1R; IGF-MTX; chronic myelomonocytic leukemia; myelodysplastic syndrome; oligoblastic acute myeloid leukemia; phase 1 study.

Publication types

  • Case Reports
  • Clinical Trial, Phase I

MeSH terms

  • Aged
  • Aged, 80 and over
  • Humans
  • Immunoconjugates / administration & dosage*
  • Immunoconjugates / adverse effects
  • Immunoconjugates / immunology
  • Insulin-Like Growth Factor I / administration & dosage
  • Insulin-Like Growth Factor I / immunology
  • Male
  • Methotrexate / administration & dosage*
  • Methotrexate / adverse effects
  • Molecular Targeted Therapy
  • Myelodysplastic Syndromes / blood
  • Myelodysplastic Syndromes / drug therapy*
  • Myelodysplastic Syndromes / immunology
  • Myelodysplastic Syndromes / pathology
  • Neoplasm Grading
  • Receptor, IGF Type 1 / biosynthesis
  • Receptor, IGF Type 1 / immunology

Substances

  • IGF1R protein, human
  • Immunoconjugates
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1
  • Methotrexate