Reference Detail

Ref Type

PMID

Authors

J. Diamond, G. Eckhardt, L. Gluck, M. Gutierrez, C. Peterson, R. Pila, E. Benaim

Title

Phase 1 study of RX-5902, a novel orally bioavailable inhibitor of phosphorylated P68, which prevents b-catenin translocation in advanced solid tumors

Journal	Vol	Issue	Date	Pages	Journal Short Title
Ann Oncol

URL

https://www.annalsofoncology.org/article/S0923-7534(20)37682-1/fulltext

Abstract Text

Background: 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. Methods: 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. Results: 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. Conclusions: 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: NCT02003092

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References