Repare Therapeutics presented new data from Module 1 of its Phase 1/2 TRESR clinical trial, evaluating camonsertib monotherapy in patients with advanced cancers harboring ATM loss-of-function, at the European Society for Medical Oncology (ESMO) Congress 2024 in Barcelona, Spain.
The TRESR trial (NCT04497116) is a first-in-human, multi-center, open-label study designed to establish the recommended Phase 2 dose (RP2D) and schedule for camonsertib. The study assessed the safety, pharmacokinetics, and preliminary anti-tumor activity of camonsertib monotherapy in patients with solid tumors.
Camonsertib in ATM-Deficient Cancers
The oral presentation at ESMO, titled "Camonsertib (cam) monotherapy in patients (pts) with advanced cancers harboring ATM loss-of-function (LoF)," was delivered by Benedito A. Carneiro, MD, from the Legorreta Cancer Center, Division of Hematology/Oncology, The Warren Alpert Medical School, Brown University, Providence, RI.
Camonsertib (RP-3500) is a potential leading ATR inhibitor being developed by Repare Therapeutics. ATM (ataxia-telangiectasia mutated) is a protein kinase that plays a crucial role in DNA damage repair. Loss-of-function mutations in ATM can lead to genomic instability and increased susceptibility to cancer. Tumors with ATM loss-of-function may be particularly sensitive to ATR inhibitors like camonsertib.
TRESR Trial Design and Objectives
The Phase 1/2 TRESR trial is a dose-escalation and expansion study. Module 1 focused on determining the RP2D of camonsertib monotherapy. The trial enrolled patients with advanced solid tumors who had ATM loss-of-function. The primary objectives included assessing the safety and tolerability of camonsertib, as well as characterizing its pharmacokinetic profile. Secondary objectives included evaluating preliminary anti-tumor activity, such as objective response rate (ORR) and duration of response (DoR).
Repare Therapeutics' Precision Oncology Approach
Repare Therapeutics utilizes its proprietary synthetic lethality approach through the SNIPRx® platform to discover and develop targeted cancer therapies. Their pipeline includes other clinical-stage assets such as lunresertib (RP-6306), a PKMYT1 inhibitor, and RP-1664, a PLK4 inhibitor, as well as preclinical programs targeting Polθ ATPase and other undisclosed targets.
