On February 15, 2024 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported the first patient has been dosed in the Company’s Phase 1 LIONS (PLK4 Inhibitor in Advanced Solid Tumors) clinical trial evaluating RP-1664, a potential first-in-class, highly selective, oral polo-like kinase 4 (PLK4) inhibitor, for the monotherapy treatment of adult and adolescent patients enriched for TRIM37-high solid tumors (Press release, Repare Therapeutics, FEB 15, 2024, View Source [SID1234640172]).
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"RP-1664 exhibited deep tumor growth inhibition and regressions in multiple TRIM37-high solid tumor and neuroblastoma xenograft models, both internally and in collaboration with Children’s Hospital of Philadelphia. After evaluating safety in the LIONS clinical trial, we expect to move rapidly into a Phase 1/2 clinical trial in high risk, recurrent pediatric neuroblastoma, in which patients have a high prevalence of TRIM37-altered tumors and limited treatment options," said Maria Koehler, MD, PhD, Executive Vice President and Chief Medical Officer of Repare. "RP-1664 is Repare’s third internally-developed clinical therapeutic candidate, a testament to the productivity of our platform."
The LIONS clinical trial (NCT06232408) is a first-in-human, multicenter, open-label Phase 1 study to investigate safety, pharmacokinetics, pharmacodynamics and the preliminary efficacy of RP-1664. The clinical trial is expected to enroll approximately 80 patients with molecularly selected advanced solid tumors, including those with gain or amplification of TRIM37, among other genetic alterations. The primary endpoints are to determine the safety, tolerability, dose and schedule of RP-1664 and assess any early antitumor activity.
About RP-1664
RP-1664 is a potential first-in-class, highly selective, oral PLK4 inhibitor designed to harness the synthetic lethal relationship with TRIM37 amplification or overexpression in solid tumors. Tumors rely on PLK4 for centriole biogenesis in S-phase of the cell cycle when TRIM37, an E3 ligase that reduces pericentriolar material, is high. Preclinical studies demonstrate that RP-1664 selectively inhibits PLK4 and drives potent synthetic lethality in TRIM37-high tumor models, both in vitro and in vivo. Elevated TRIM37 is a feature found across a range of solid tumors and in approximately 80% of all high-grade neuroblastomas. RP-1664 is the only selective PLK4 inhibitor known to be in the clinic.