NEW YORK – Repare Therapeutics said on Wednesday that it has dosed the first patient in a Phase I/II trial ongoing at the MD Anderson Cancer Center evaluating its ATR inhibitor RP-3500 in genomically altered solid tumors.
The Phase I/II dose-escalation and expansion trial, called the Treatment Enabled by SNIPRx (TRESR) study, will enroll approximately 230 patients with advanced solid tumors of any histology that harbor gene alterations that Repare's SNIPRx platform has predicted preclinically may be sensitive to RP-3500 alone or in combination with the PARP inhibitor talazoparib (Pfizer's Talzenna).
The SNIPRx platform uses genome-wide CRISPR-based screening to identify patients most likely to benefit from Repare's therapies based on the genetic profile of their tumors. Genetic alterations of interest include genome instability-related genomic alterations such as those in the ATM gene.
In preclinical studies, RP-3500 elicited sustained responses in solid tumors with specific molecular alterations determined by SNIPRx. When RP-3500 was combined with PARP inhibitors and tested preclinically against solid tumors with SNIPRx-identified genetic alterations, the regimen also demonstrated anti-tumor effects.
Repare is collaborating with Pfizer on this study, and under the partnership, Pfizer will provide talazoparib for the clinical trial.
The primary endpoint of the Phase I portion of the study will be safety, tolerability, and determination of a recommended Phase II dose. The Phase II monotherapy portion will evaluate the efficacy of RP-3500 in biomarker-selected tumors. Researchers will also assess the drug's anti-tumor activity, pharmacokinetics, and pharmacodynamics and confirm the accuracy of the predictive biomarkers.