Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours
David S. Hong, Yoon‐Koo Kang, Mitesh J. Borad, Jasgit C. Sachdev, Samuel Ejadi, Ho Yeong Lim, Andrew Brenner, Keunchil Park, Jae‐Lyun Lee, Tae‐You Kim, SangJoon Shin, Carlos Becerra, Gerald S. Falchook, Jay Stoudemire, Desiree Martin, Kevin Kelnar, Heidi J. Peltier, Vinícius Bonato, Andreas G. Bader, Susan Smith, Sinil Kim, Vincent O’Neill, Muhammad Shaalan Beg
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.