| Title |
Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in patients with advanced solid tumors
|
|---|---|
| Published in |
Investigational New Drugs, December 2016
|
| DOI | 10.1007/s10637-016-0407-y |
| Pubmed ID | |
| Authors |
Muhammad S. Beg, Andrew J. Brenner, Jasgit Sachdev, Mitesh Borad, Yoon-Koo Kang, Jay Stoudemire, Susan Smith, Andreas G. Bader, Sinil Kim, David S. Hong |
| Abstract |
Purpose Naturally occurring tumor suppressor microRNA-34a (miR-34a) downregulates the expression of >30 oncogenes across multiple oncogenic pathways, as well as genes involved in tumor immune evasion, but is lost or under-expressed in many malignancies. This first-in-human, phase I study assessed the maximum tolerated dose (MTD), safety, pharmacokinetics, and clinical activity of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumors. Patients and Methods Adult patients with solid tumors refractory to standard treatment were enrolled in a standard 3 + 3 dose escalation trial. MRX34 was given intravenously twice weekly (BIW) for three weeks in 4-week cycles. Results Forty-seven patients with various solid tumors, including hepatocellular carcinoma (HCC; n = 14), were enrolled. Median age was 60 years, median prior therapies was 4 (range, 1-12), and most were Caucasian (68%) and male (57%). Most common adverse events (AEs) included fever (all grade %/G3%: 64/2), fatigue (57/13), back pain (57/11), nausea (49/2), diarrhea (40/11), anorexia (36/4), and vomiting (34/4). Laboratory abnormalities included lymphopenia (G3%/G4%: 23/9), neutropenia (13/11), thrombocytopenia (17/0), increased AST (19/4), hyperglycemia (13/2), and hyponatremia (19/2). Dexamethasone premedication was required to manage infusion-related AEs. The MTD for non-HCC patients was 110 mg/m(2), with two patients experiencing dose-limiting toxicities of G3 hypoxia and enteritis at 124 mg/m(2). The half-life was >24 h, and Cmax and AUC increased with increasing dose. One patient with HCC achieved a prolonged confirmed PR lasting 48 weeks, and four patients experienced SD lasting ≥4 cycles. Conclusion MRX34 treatment with dexamethasone premedication was associated with acceptable safety and showed evidence of antitumor activity in a subset of patients with refractory advanced solid tumors. The MTD for the BIW schedule was 110 mg/m(2) for non-HCC and 93 mg/m2 for HCC patients. Additional dose schedules of MRX34 have been explored to improve tolerability. |
Mendeley readers
The data shown below were compiled from readership statistics for 448 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 448 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 88 | 20% |
| Student > Bachelor | 54 | 12% |
| Student > Master | 53 | 12% |
| Researcher | 52 | 12% |
| Other | 19 | 4% |
| Other | 59 | 13% |
| Unknown | 123 | 27% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 130 | 29% |
| Medicine and Dentistry | 51 | 11% |
| Agricultural and Biological Sciences | 41 | 9% |
| Pharmacology, Toxicology and Pharmaceutical Science | 20 | 4% |
| Immunology and Microbiology | 11 | 2% |
| Other | 55 | 12% |
| Unknown | 140 | 31% |
Attention Score in Context
This research output has an Altmetric Attention Score of 11. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 March 2023.
All research outputs
#2,807,909
of 23,485,204 outputs
Outputs from Investigational New Drugs
#64
of 1,196 outputs
Outputs of similar age
#56,213
of 419,198 outputs
Outputs of similar age from Investigational New Drugs
#1
of 9 outputs
Altmetric has tracked 23,485,204 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,196 research outputs from this source. They receive a mean Attention Score of 4.8. This one has done particularly well, scoring higher than 94% of its peers.
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