RX-5902 is a novel compound that targets phosphorylated p68 RNA helicase (also known as DDX5), a member of the DEAD box family of RNA helicases. Phosphorylated p68 may play a vital role in cell proliferation and tumor/cancer progression through inhibition of β-catenin translocation. We report preliminary results of the Phase 1 study of RX-5902 as a single agent to treat advanced solid tumors.
The dose finding portion of the Phase 1 study (NCT02003092) was designed to evaluate safety, tolerability and dose limiting toxicities, to identify the maximum tolerated dose and a recommended phase 2 dose and schedule (RP2D). Secondary objectives were pharmacokinetics (PK) and antitumor activity (RECIST v1.1). Eligible subjects (aged ≥ 18 years), with relapsed/refractory solid tumors that had been heavily pretreated, received oral RX-5902 ranging from 25 mg to 350 mg and administered at 1, 3, 5 or 7 times per week for 3 weeks followed by 1 week of rest or for 4 weeks without rest.
As of May 2017, 35 subjects (23 Females, 12 males) were treated with oral RX-5902. The dose limiting toxicities were G4 hyponatremia (n = 1) and G3 fatigue (n = 1) at 300 mg administered daily for 4 weeks. The maximum tolerated dose of 250 mg, will be studied further in the Phase 2a portion. Of the 35 subjects treated, 15 subjects (breast ER+/PR+/Her2-, triple negative breast (n = 2), cervical (n = 2), neuroendocrine (n = 3), paraganglioma, colorectal (N = 3), pancreatic, ovarian, head and neck cancers) experienced stable disease; 2 subjects have received treatment for > 2.5 years. The most common related adverse events were G1/G2 anorexia, G1/G2 nausea, G1/G2 vomiting, G1/G2 diarrhea, G1 weight loss and G1/G2 fatigue. Oral RX-5902 was bioavailable with median Tmax of 2 hours and median elimination half-life of 12 hours.
Data from this study support that RX-5902 is safe and well-tolerated at the doses and schedules tested. The RP2D of 250 mg of RX-5902 administered daily for 5 consecutive days for 4 weeks is being studied further in metastatic triple negative breast cancer in the Phase 2 portion of this study.
Clinical trial identification
Legal entity responsible for the study
Rexahn Pharmaceuticals, Inc.
Rexahn Pharmaceuticals, Inc
C. Peterson, R. Pila, E. Benaim: Employee of Rexahn Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.