RP-3467 + olaparib

**RP-3467 + olaparib** is an investigational oral combination therapy being studied for advanced solid tumors, including metastatic breast cancer, metastatic castration-resistant prostate cancer, locally advanced or metastatic epithelial ovarian cancer, and pancreatic adenocarcinoma. RP-3467 is a small molecule inhibitor targeting DNA polymerase theta (Polθ) ATPase/helicase, a key enzyme involved in certain DNA repair pathways. Olaparib (brand name Lynparza) is an FDA-approved poly-ADP ribose polymerase (PARP) inhibitor, widely used as a targeted therapy for cancers with defective homologous recombination DNA repair, such as those with BRCA mutations. Mechanistically, combining RP-3467 and olaparib seeks to enhance synthetic lethality by simultaneously blocking complementary DNA repair pathways, aiming to increase anti-tumor efficacy and combat PARP inhibitor resistance. RP-3467 is developed by Repare Therapeutics; olaparib is marketed by AstraZeneca. The combination is currently being assessed in a Phase 1 clinical trial (POLAR trial, NCT06560632) to determine safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity[1][2][3][4][5][6][7][8][9][10].

Other names

RP-3467 + olaparib