Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• British journal of cancer, 2020-05, Vol.122 (11), p.1630-1637

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.