RO7623066 + olaparib

**RO7623066 + olaparib** is an investigational combination therapy for advanced solid tumors, especially those with homologous recombination repair (HRR) deficiencies such as BRCA1/2 mutations. RO7623066 is an oral, selective small molecule inhibitor of ubiquitin-specific peptidase 1 (USP1), an enzyme central to the regulation of DNA repair pathways (notably, translesion synthesis and Fanconi Anemia pathway)[1][2][5]. Olaparib is a small molecule PARP inhibitor (marketed as Lynparza) that impairs DNA repair via poly(ADP-ribose) polymerase blockade. Preclinical and clinical data suggest synergy between USP1 inhibition and PARP inhibition, potentially overcoming innate or acquired resistance to PARP inhibitors in DNA repair-deficient cancer cells[1][5]. The combination has been investigated in a Phase 1 trial for safety, tolerability, and preliminary efficacy[1][3][4][5][6][9]. The most common side effect observed with the combination is anemia[1]. The trial is sponsored by Roche (Genentech) following its in-licensing of RO7623066 (KSQ-4279) from KSQ Therapeutics[2][3][4]. As of mid-2024, the combination is still in early phase clinical development, with ongoing dose-finding and expansion cohorts; recent reports indicate Roche discontinued the RO7623066 program due to disappointing efficacy results[6].

Other names

RO7623066RO-7623066RO 7623066KSQ-4279KSQ4279KSQ 4279olaparib