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

British journal of cancer, 2020-05, Vol.122 (11), p.1630-1637 [Peer Reviewed Journal]

The Author(s), under exclusive licence to Cancer Research UK 2020. ;The Author(s), under exclusive licence to Cancer Research UK 2020 ;ISSN: 0007-0920 ;EISSN: 1532-1827 ;DOI: 10.1038/s41416-020-0802-1 ;PMID: 32238921

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Title:
Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours
Author: Hong, David S ; Kang, Yoon-Koo ; Borad, Mitesh ; Sachdev, Jasgit ; Ejadi, Samuel ; Lim, Ho Yeong ; Brenner, Andrew J ; Park, Keunchil ; Lee, Jae-Lyun ; Kim, Tae-You ; Shin, Sangjoon ; Becerra, Carlos R ; Falchook, Gerald ; Stoudemire, Jay ; Martin, Desiree ; Kelnar, Kevin ; Peltier, Heidi ; Bonato, Vinicius ; Bader, Andreas G ; Smith, Susan ; Kim, Sinil ; O'Neill, Vincent ; Beg, Muhammad S
Subjects: Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - adverse effects ; Antineoplastic Agents - pharmacokinetics ; Cancer therapies ; Dexamethasone ; Dyspnea ; Female ; Fever ; Gene expression ; Hepatocellular carcinoma ; Humans ; Leukocytes ; Liposomes - adverse effects ; Liposomes - pharmacokinetics ; Liver cancer ; Male ; Maximum Tolerated Dose ; MicroRNAs ; MicroRNAs - administration & dosage ; MicroRNAs - adverse effects ; MicroRNAs - pharmacokinetics ; Middle Aged ; miRNA ; Nanoparticles - administration & dosage ; Nanoparticles - adverse effects ; Nausea ; Neoplasms - drug therapy ; Patients ; Pharmacodynamics ; Respiration ; Solid tumors ; Toxicity ; Tumors
Is Part Of: British journal of cancer, 2020-05, Vol.122 (11), p.1630-1637
Description: 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. 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. 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/m for hepatocellular carcinoma (HCC) and 93 mg/m 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). 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. NCT01829971.
Publisher: England: Nature Publishing Group
Language: English
Identifier: ISSN: 0007-0920
EISSN: 1532-1827
DOI: 10.1038/s41416-020-0802-1
PMID: 32238921
Source: Geneva Foundation Free Medical Journals at publisher websites
MEDLINE
PubMed Central
ProQuest Central

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

The Author(s), under exclusive licence to Cancer Research UK 2020. ;The Author(s), under exclusive licence to Cancer Research UK 2020 ;ISSN: 0007-0920 ;EISSN: 1532-1827 ;DOI: 10.1038/s41416-020-0802-1 ;PMID: 32238921

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