On March 7, 2022 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company enabled by its proprietary synthetic lethality approach to the discovery and development of novel therapeutics, reported the presentation of monotherapy dose selection and safety data from its Phase 1/2 TRESR (Treatment Enabled by SNIPRx) clinical trial of RP-3500 at the 2022 ESMO (Free ESMO Whitepaper) Targeted Anticancer Therapies (TAT) Congress (Press release, Repare Therapeutics, MAR 7, 2022, View Source [SID1234609608]). RP-3500 is a potent and selective oral small molecule inhibitor of ATR (Ataxia-Telangiectasia and Rad3-related protein kinase) in development for the treatment of solid tumors with specific synthetic-lethal genomic alterations, including those in the ATM gene (Ataxia-Telangiectasia mutated kinase) .
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"The data featured today at ESMO (Free ESMO Whitepaper) TAT continues to show that RP-3500 is well tolerated. The dose optimization approach used in the trial provides robust evidence to support the recommended phase two dose and schedule in our ongoing trials. We believe these data confirm a well differentiated and likely best in class profile of RP-3500," said Maria Koehler, MD, PhD, Chief Medical Officer of Repare. "We look forward to presenting updated clinical data from 120 patients enrolled in the Phase 1/2 TRESR trial in the first half of this year."
Key Findings from the TRESR Phase 1 Safety Data:
TRESR is a first-in-human, multi-center, open-label Phase 1/2 dose-escalation and expansion clinical trial, designed to establish the recommended Phase 2 dose (RP2D) and schedule, evaluate safety and pharmacokinetics and identify preliminary anti-tumor activity associated with RP-3500, given alone and in combination with talazoparib. The study also examined biomarker responses and their relationship with RP-3500 antitumor activity.
Safety data presented in the oral presentation include a comprehensive safety analysis from three monotherapy dosing schedules of RP-3500 at therapeutic doses:
120mg once daily, 3 days on/4 days off
160mg once daily, 3 days on/4 days off
160mg once daily, 3 days on/4 days off, 2 weeks on/1 week off
Highlights from the data presented at ESMO (Free ESMO Whitepaper) TAT congress include:
This comprehensive safety analysis confirmed the acceptable tolerability of the recommended phase 2 dose (160mg 3 days/4 days off)
Anemia was the most common reported toxicity with less than 25% of patients experiencing grade 3 toxicities
A dose modification plan that includes 2 alternative dosing schedules was established to mitigate the on-target toxicity of anemia and maintain patients on an RP-3500 dosing schedule that targets antitumor activity
A nomogram, based on cycle 1 assessment of toxicities, is being prospectively evaluated to identify patients at increased risk of anemia and inform early intervention
Oral Presentation Details:
Title: Comprehensive Dose-Finding Strategy for Single-Agent RP-3500, a Highly Selective Inhibitor of Ataxia-Telangiectasia and Rad3-Related (ATR) Kinase
Presenter: Dr. Elisa Fontana, Sarah Cannon Research Institute UK
Abstract Number: 202
Session Title: DNA Damage Repair
About Repare Therapeutics’ SNIPRx Platform
Repare’s SNIPRx platform is a genome-wide CRISPR-based screening approach that utilizes proprietary isogenic cell lines to identify novel and known synthetic lethal gene pairs and the corresponding patients who are most likely to benefit from the Company’s therapies based on the genetic profile of their tumors. Repare’s platform enables the development of precision therapeutics in patients whose tumors contain one or more genomic alterations identified by SNIPRx screening, in order to selectively target those patients most likely to achieve clinical benefit from resulting product candidates.