Repare Therapeutics presents initial data from Phase 1/2 TRESR, ATTACC trials

Repare Therapeutics presented initial data from its ongoing Phase 1/2 TRESR clinical trial evaluating camonsertib, a potent and selective oral small molecule inhibitor of ATR, in combination with a poly polymerase inhibitor, talazoparib, and initial data from its ongoing Phase 1b/2 ATTACC clinical trial, evaluating camonsertib in combination with two additional PARPis, niraparib or olaparib, in patients with advanced solid tumors. The data involving novel combinations of low doses of camonsertib and three different PARPis are featured today at the 2023 AACR Annual Meeting in a clinical plenary session titled, "Safety and efficacy of three PARP inhibitors combined with the ataxia telangiectasia- and Rad3-related kinase inhibitor camonsertib in patients with solid tumors harboring DNA damage response alterations". This study population comprised patients with a broad range of historically difficult to treat tumors, including patients with platinum-resistant tumors, patients who had either recurred or progressed during or after treatment with PARPis, and patients who had developed known BRCA-reversion mutations. Key Initial Findings from the TRESR Phase 1/2 and ATTACC 1b/2 PARPi Combination Studies: TRESR is a first-in-human, multi-center, open-label Phase 1/2 dose-escalation and expansion study, designed to establish the recommended Phase 2 dose and schedule, evaluate safety and pharmacokinetics and identify preliminary anti-tumor activity associated with camonsertib, given alone and in combination with talazoparib or in combination with gemcitabine. ATTACC is a first-in-human, multi-center, open-label Phase 1b/2 dose-escalation and expansion study, designed to evaluate safety and pharmacokinetics and identify preliminary anti-tumor activity associated with camonsertib in combination with niraparib or olaparib. The clinical plenary session described initial combination Phase 1/2 results from 107 patients, of which 90 patients were evaluable for efficacy treated at least 13 weeks prior to the data cutoff of February 27, 2023. Key highlights from the data presented at the 2023 AACR Annual Meeting include: Camonsertib combination resulted in durable clinical benefit across tumor types and different genomic alterations, regardless of choice of PARPi and presence of platinum resistance. Overall clinical benefit rate for all patients was 48%. Patients with platinum-resistant tumors had an overall response rate of 12% and CBR of 49%, and benefited similarly to non-platinum-resistant tumors. Compelling results were observed particularly in patients with advanced ovarian cancer. In these patients, overall response was 32%, CBR was 58% and median progression-free survival was approximately 7 months with treatment greater than16 weeks and ongoing in 9 patients. Early ctDNA molecular responses in 66% of evaluable patients confirms antitumor activity of low dose, intermittent PARPi + ATRi therapy. The molecular response rate was significantly higher in patients with clinical benefit compared to those without, confirming treatment effect. Molecular responses were observed in patients with prior PARPi exposure and platinum resistance. Camonsertib combinations appear to be well tolerated. Dose limiting toxicity in 68 patients treated with the proposed combination doses were related to myelotoxicity only. No prophylactic growth factors were required when administering the PARPis at evaluated doses.