New Agent Targeting Epigenetic Modifications Shows Activity in Advanced Cancer
In a dose-escalation phase I study reported in The Lancet Oncology, Reid et al found that RRx-001, a representative of a new class of compounds called dinitroazetidines (sourced from the aerospace industry) that act on the tumor microenvironment, had activity in advanced cancers and a promising safety profile. RRx-001 is activated by hypoxia and induces generation of reactive oxygen and nitrogen species that can epigenetically modulate DNA methylation, histone deacetylation, and lysine demethylation.
Study Details
In the study, 25 patients with advanced, malignant, incurable solid tumors from the University of California, San Diego, and Sarah Cannon Research Institute received intravenous infusions of RRx-001 at increasing doses of 10 mg/m², 16.7 mg/m², 24.6 mg/m², 33 mg/m², 55 mg/m², and 83 mg/m² once or twice weekly for ≥ 4 weeks.
Toxicity and Responses
The most common drug-related adverse event of any grade was pain at the injection site, with other common events including arm swelling or edema (32%) and vein hardening (28%). No dose-limiting toxicities were observed. However, time constraints for management of infusion pain resulted in a maximally feasible dose of 83 mg/m².
Of 21 evaluable patients, 1 (5%) had a partial response, 14 (67%) had stable disease, and 6 (29%) had progressive disease at 8 weeks. After RRx-001 treatment, 4 patients were rechallenged with a treatment to which they had become refractory, with all 4 achieving response.
The investigators concluded: “RRx-001 is a well-tolerated novel compound without clinically significant toxic effects at the tested doses. Preliminary evidence of activity is promising and, on the basis of all findings, a dose of 16.7 mg/m² was recommended as the targeted dose for phase 2 trials.”
Tony Reid, MD, of the University of California, San Diego, is the corresponding author of The Lancet Oncology article.
The study was funded by EpicentRx (formerly RadioRx). For full disclosures of the study authors, visit www.thelancet.com/journals/lanonc.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
