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

David S. Hong, Yoon Koo Kang, Mitesh Borad, Jasgit Sachdev, Samuel Ejadi, Ho Yeong Lim, Andrew J. Brenner, Keunchil Park, Jae Lyun Lee, Tae You Kim, Sangjoon Shin, Carlos R. Becerra, Gerald Falchook, Jay Stoudemire, Desiree Martin, Kevin Kelnar, Heidi Peltier, Vinicius Bonato, Andreas G. Bader, Susan SmithSinil Kim, Vincent O’Neill, Muhammad S. Beg

Research output: Contribution to journalArticlepeer-review

473 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1630-1637
Number of pages8
JournalBritish Journal of Cancer
Issue number11
StatePublished - May 26 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours'. Together they form a unique fingerprint.

Cite this