RP-3467

RP-3467 is a novel, orally administered small molecule inhibitor targeting the ATPase activity of DNA polymerase theta (Polθ). Developed by Repare Therapeutics, it is designed as a potential best-in-class Polθ ATPase inhibitor. The drug has demonstrated strong preclinical efficacy, including complete and durable tumor regressions when combined with olaparib (a PARP inhibitor), without additive toxicities. Its primary mechanism involves inhibiting Polθ-mediated DNA repair pathways, which are particularly relevant in tumors with homologous recombination deficiencies or resistance to PARP inhibitors. The ongoing Phase 1 POLAR clinical trial is evaluating its safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity both as monotherapy and in combination with olaparib in adults with advanced solid tumors such as ovarian cancer, breast cancer, castration-resistant prostate cancer, and pancreatic adenocarcinoma[1][2][3][4][5][6].

Other names

RP 3467RP3467RP-3467