Статья

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

David S. HongThe University of Texas MD Anderson Cancer Center, Houston, TX, USA. [email protected]Yoon‐Koo KangAsan Medical Center, Seoul, South KoreaMitesh J. BoradMayo Clinic Cancer Center, Scottsdale, AZ, USAJasgit C. SachdevScottsdale Healthcare Research Institute, Scottsdale, AZ, USASamuel EjadiUniversity of California Irvine Medical Center, Orange, CA, USAHo Yeong LimSamsung Medical Center, Seoul, KoreaAndrew BrennerThe University of Texas Health Science Center at San Antonio, San Antonio, TX, USAKeunchil ParkSamsung Medical Center, Seoul, KoreaJae‐Lyun LeeAsan Medical Center, Seoul, South KoreaTae‐You KimSeoul National University Hospital, Seoul, South KoreaSangJoon ShinSeverance Hospital, Seoul, South KoreaCarlos BecerraTexas Oncology-US Oncology-Baylor University Medical Center, Dallas, TX, USAGerald S. FalchookSarah Cannon Research Institute at HealthONE, Denver, CO, USAJay StoudemireMirna Therapeutics, Austin, TX, USADesiree MartinMirna Therapeutics, Austin, TX, USAKevin KelnarMirna Therapeutics, Austin, TX, USAHeidi J. PeltierMirna Therapeutics, Austin, TX, USAVinícius BonatoMirna Therapeutics, Austin, TX, USAAndreas G. BaderMirna Therapeutics, Austin, TX, USASusan SmithMirna Therapeutics, Austin, TX, USASinil KimMirna Therapeutics, Austin, TX, USAVincent O’NeillMirna Therapeutics, Austin, TX, USAMuhammad Shaalan BegThe University of Texas Southwestern Medical Center, Dallas, TX, USA

2020en

ABI

Аннотация

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.

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Идентификаторы

DOI: 10.1038/s41416-020-0802-1

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Цитирований: 4Использованных источников: 0

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