Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours

Br J Cancer. 2020 May;122(11):1630-1637. doi: 10.1038/s41416-020-0802-1. Epub 2020 Apr 2.


Background: In this first-in-human, Phase 1 study of a microRNA-based cancer therapy, the recommended Phase 2 dose (RP2D) of MRX34, a liposomal mimic of microRNA-34a (miR-34a), was determined and evaluated in patients with advanced solid tumours.

Methods: Adults with various solid tumours refractory to standard treatments were enrolled in 3 + 3 dose-escalation cohorts and, following RP2D determination, expansion cohorts. MRX34, with oral dexamethasone premedication, was given intravenously daily for 5 days in 3-week cycles.

Results: Common all-cause adverse events observed in 85 patients enrolled included fever (% all grade/G3: 72/4), chills (53/14), fatigue (51/9), back/neck pain (36/5), nausea (36/1) and dyspnoea (25/4). The RP2D was 70 mg/m2 for hepatocellular carcinoma (HCC) and 93 mg/m2 for non-HCC cancers. Pharmacodynamic results showed delivery of miR-34a to tumours, and dose-dependent modulation of target gene expression in white blood cells. Three patients had PRs and 16 had SD lasting ≥4 cycles (median, 19 weeks, range, 11-55).

Conclusion: MRX34 treatment with dexamethasone premedication demonstrated a manageable toxicity profile in most patients and some clinical activity. Although the trial was closed early due to serious immune-mediated AEs that resulted in four patient deaths, dose-dependent modulation of relevant target genes provides proof-of-concept for miRNA-based cancer therapy.

Clinical trial registration: NCT01829971.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / pharmacokinetics
  • Female
  • Humans
  • Liposomes / adverse effects
  • Liposomes / pharmacokinetics
  • Male
  • Maximum Tolerated Dose
  • MicroRNAs / administration & dosage*
  • MicroRNAs / adverse effects*
  • MicroRNAs / pharmacokinetics
  • Middle Aged
  • Nanoparticles / administration & dosage
  • Nanoparticles / adverse effects
  • Neoplasms / drug therapy*


  • Antineoplastic Agents
  • Liposomes
  • MIRN34 microRNA, human
  • MicroRNAs

Associated data