Repare Therapeutics Inc. (Nasdaq: RPTX) announced it will present initial topline safety, tolerability and early efficacy data from the Phase 1 LIONS clinical trial at the 37th AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, scheduled for October 22-26, 2025 in Boston, MA. The presentation marks the first clinical data disclosure for RP-1664, the company's potential first-in-class PLK4 inhibitor.
First-in-Human Trial Design
The LIONS clinical trial (NCT06232408) represents a first-in-human, multicenter, open-label Phase 1 study designed to investigate the safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of RP-1664. The study focuses on monotherapy treatment of adult and adolescent patients with TRIM37-high solid tumors.
Dr. Benjamin Herzberg from Columbia University will present the findings in a poster titled "Preliminary safety and antitumor activity of RP-1664, a first-in-class PLK4 inhibitor, as monotherapy in advanced solid tumors with and without TRIM37 amplification." The presentation is scheduled for Saturday, October 25, from 12:30 p.m. to 4:00 p.m. ET in Level 2, Exhibit Hall D.
Novel Mechanism of Action
RP-1664 is designed as a highly selective, oral PLK4 inhibitor that harnesses the synthetic lethal relationship with TRIM37 amplification or overexpression in solid tumors. The drug targets a specific vulnerability in cancer cells where tumors rely on PLK4 for centriole biogenesis during S-phase of the cell cycle when TRIM37, an E3 ligase that reduces pericentriolar material, is elevated.
Preclinical studies have demonstrated that RP-1664 selectively inhibits PLK4 and drives potent synthetic lethality in TRIM37-high tumor models, both in vitro and in vivo. According to Repare Therapeutics, RP-1664 is the only selective PLK4 inhibitor currently known to be in clinical development.
Significant Patient Population
The therapeutic approach addresses a substantial patient population, as elevated TRIM37 is found across a range of solid tumors. Notably, approximately 80% of all high-grade neuroblastomas exhibit this biomarker, representing a significant unmet medical need in pediatric and adolescent oncology.
Company Background
Repare Therapeutics is a clinical-stage precision oncology company that utilizes a proprietary synthetic lethality approach for discovering and developing novel therapeutics. The company's clinical-stage pipeline includes RP-3467, a Phase 1 Polθ ATPase inhibitor, alongside RP-1664. The company focuses on highly targeted cancer therapies centered on genomic instability, including DNA damage repair mechanisms.
The poster presentation materials will be made available on the Scientific Resources page of the Repare Therapeutics website at the start of the presentation session.
