A Phase 1 dose-escalation study to evaluate safety, pharmacokinetics and pharmacodynamics of AsiDNA, a first-in-class DNA repair inhibitor, administered intravenously in patients with advanced solid tumours

Br J Cancer. 2020 Nov;123(10):1481-1489. doi: 10.1038/s41416-020-01028-8. Epub 2020 Aug 25.


Background: AsiDNA, a first-in-class oligonucleotide-mimicking double-stranded DNA breaks, acts as a decoy agonist to DNA damage response in tumour cells. It also activates DNA-dependent protein kinase and poly (adenosine diphosphate [ADP]-ribose) polymerase enzymes that induce phosphorylation of H2AX and protein PARylation.

Methods: The aim of this Phase 1 study was to determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), safety and pharmacokinetics/pharmacodynamics of AsiDNA administered daily for 3 days in the first week then weekly thereafter. Twenty-two patients with advanced solid tumours were enrolled in 5 dose levels: 200, 400, 600, 900, and 1300 mg, using a 3 + 3 design.

Results: The MTD was not reached. IV AsiDNA was safe. Two DLTs (grade 4 and grade 3 hepatic enzymes increased at 900 and 1300 mg), and two related SAE at 900 mg (grade 3 hypotension and grade 4 hepatic enzymes increased) were reported. AsiDNA PK increased proportionally with dose. A robust activation of DNA-PK by a significant posttreatment increase of γH2AX was evidenced in tumour biopsies.

Conclusion: The dose of 600 mg was identified as the optimal dose for further clinical development.

Clinical trial registration: Clinical trial registration (NCT number): NCT03579628.

Publication types

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

MeSH terms

  • Administration, Intravenous
  • Adult
  • Aged
  • Belgium
  • Cholesterol / administration & dosage
  • Cholesterol / adverse effects
  • Cholesterol / analogs & derivatives*
  • Cholesterol / pharmacokinetics
  • DNA / administration & dosage*
  • DNA / adverse effects*
  • DNA / pharmacokinetics*
  • DNA Repair / drug effects
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Female
  • France
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology


  • DT01 compound
  • DNA
  • Cholesterol

Associated data

  • ClinicalTrials.gov/NCT03579628