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Ref Type Journal Article
PMID (29992354)
Authors Furuse J, Kurata T, Okano N, Fujisaka Y, Naruge D, Shimizu T, Kitamura H, Iwasa T, Nagashima F, Nakagawa K
Title An early clinical trial of Salirasib, an oral RAS inhibitor, in Japanese patients with relapsed/refractory solid tumors.
Journal Cancer chemotherapy and pharmacology
Vol
Issue
Date 2018 Jul 10
URL
Abstract Text Patients with RAS-positive tumors respond poorly to chemotherapies and have a few treatment options. Salirasib is an oral RAS inhibitor that competitively blocks the membrane association of RAS proteins. The aim of this phase I multiple-ascending-dose clinical trial was to investigate the safety and pharmacokinetics of Salirasib in Japanese patients with relapsed/refractory solid tumors and to explore its efficacy.Salirasib was started at a dose of 100-mg twice-daily and escalated to a maximum of 1000-mg twice-daily from days 1 to 21 of a 28-day regimen. The pharmacokinetics was evaluated on days 1 and 21. Dose-limiting toxicity (DLT) and adverse events (AEs) were monitored throughout the trial. Patients with stable disease or better repeated the dosing regimen.A total of 21 patients received Salirasib. Among 14 patients tested, 4 had KRAS mutations. Cmax and AUCinf were maximal at 800 mg. No maximum tolerable dose was discerned, as no DLT was observed in any dosing group. The most frequently observed AEs were gastrointestinal disturbances, including diarrhea, abdominal pain, and nausea. No AEs led to discontinuation. All patients completed the first regimen and 11 patients repeated the regimen (median: 2 cycles; range: 1-13). Patients with KRAS mutations showed median progression-free survival of 227 days (range: 79-373).Salirasib was safe and well tolerated in Japanese patients, and 800-mg twice-daily is recommended for phase II trials. Although the number of participants with KRAS mutations was limited, the remarkably long progression-free period warrants further investigation.JAPIC Clinical Trials Information; JapicCTI-121751.

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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
Salirasib KD032 RAS Inhibitor (Pan) 8 Salirasib, S-trans,trans-farnesylthiosalycilic acid, disrupts the interaction of RAS with the cell membrane, thereby preventing RAS signaling (PMID: 20528225, PMID: 29992354, PMID: 29901113).
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
Unknown unknown Advanced Solid Tumor not applicable Salirasib Phase I Actionable In a Phase I clinical trial, Salirasib treatment was well tolerated in Japanese patients with advanced solid tumors (n=21) and resulted in a median progression-free survival of 53 days (PMID: 29992354). 29992354