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

Abstract

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: 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.

Shown for reading. Its publisher allows quoting it, not republishing it.

References 51

1. 1.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

2. 2.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

3. 3.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

4. 4.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

5. 5.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

6. 6.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

7. 7.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

8. 8.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

9. 9.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

10. 10.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

11. 11.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

12. 12.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

13. 13.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

14. 14.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

15. 15.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

16. 16.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

17. 17.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

18. 18.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

19. 19.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

20. 20.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

21. 21.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

22. 22.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

23. 23.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

24. 24.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

25. 25.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

26. 26.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

27. 27.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

28. 28.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

29. 29.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

30. 30.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

31. 31.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

32. 32.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

33. 33.
    MicroRNA miR-34 Inhibits Human Pancreatic Cancer Tumor-Initiating Cells · 2009

    No notice
34. 34.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

35. 35.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

36. 36.
    Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres · 2008

    No notice
37. 37.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

38. 38.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

39. 39.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

40. 40.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

41. 41.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

42. 42.
    PDL1 Regulation by p53 via miR-34 · 2015

    No notice
43. 43.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

44. 44.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

45. 45.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

46. 46.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

47. 47.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

48. 48.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

49. 49.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

50. 50.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

51. 51.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

Cited by papers we hold 17

• Landscape of small nucleic acid therapeutics: moving from the bench to the clinic as next-generation medicines · 2025
  No notice
• Targeting epigenetic regulators as a promising avenue to overcome cancer therapy resistance · 2025
  No notice
• MicroRNA in cancer therapy: breakthroughs and challenges in early clinical applications · 2025
  No notice
• Trials and Tribulations of MicroRNA Therapeutics · 2024
  No notice
• Epigenetics-targeted drugs: current paradigms and future challenges · 2024
  No notice
• MicroRNA: trends in clinical trials of cancer diagnosis and therapy strategies · 2023
  No notice
• Potential in anti-cancer therapy using RNA - overview of therapies · 2022
  Not checked
• Nanoparticle delivery of miR-21-3p sensitizes melanoma to anti-PD-1 immunotherapy by promoting ferroptosis · 2022
  No notice
• Targeting non-coding RNAs to overcome cancer therapy resistance · 2022
  No notice
• MicroRNAs as therapeutic targets in cardiovascular disease · 2022
  No notice
• miRNA: A Promising Therapeutic Target in Cancer · 2022
  No notice
• MicroRNA Therapeutics in Cancer: Current Advances and Challenges · 2021
  No notice
• Targeting mutant p53 for cancer therapy: direct and indirect strategies · 2021
  No notice
• Non-coding RNA in cancer · 2021
  No notice
• MicroRNA-34a: Potent Tumor Suppressor, Cancer Stem Cell Inhibitor, and Potential Anticancer Therapeutic · 2021
  No notice
• A Comprehensive Review of Cancer MicroRNA Therapeutic Delivery Strategies · 2020
  No notice
• Non-coding RNAs in cancer: platforms and strategies for investigating the genomic “dark matter” · 2020
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.