An open-label, multicenter, randomized Phase 2 study of the ATR inhibitor M1774 in combination with other DNA damage response inhibitors in participants with BRCA mutant and/or homologous recombination deficiency (HRD)-positive epithelial ovarian cancer that progressed on prior PARP inhibitor therapy

This is an Open-Label , multicenter Phase 2 study to investigate the safety and efficiency of treatment combination of tuvusertib with other drugs such as niraparib or lartesertib in patients with epithelial ovarian cancer after the disease progression while on treatment with a class of drug named poly adenosine diphosphate-ribose polymerase inhibitors (PARPi). Deoxyribonucleic acid (DNA) is material found in all human cells and plays an important part in the body. However, DNA damage occurs and if not repaired, the cells die. There are certain proteins required for the repair of these cells such as ATR (ataxia telangiectasia mutated and Rad3-related), ATM (ataxia telangiectasia mutated) and PARP (poly adenosine diphosphate-ribose polymerase). Stopping these proteins from working, will cause damage and death to cancer cells . Tuvusertib and Latesertib are investigational drugs designed to block the ATR protein that is involved in DNA repair from working, by so doing the hope is that the cancer cells will die. The effects of the treatment will be monitored by assessing the progression of the tumour, whether it disappears, shrinks or gets worse. The study will consist of 2 Parts: - Part A: the purpose of Part A is to determine whether any or both combination treatments ‘tuvusertib + niraparib’ or ‘tuvusertib + lartesertib’ work against epithelial ovarian cancer which progressed on treatment with PARP inhibitors, and if so, which one works better. All the drugs will be taken orally.- Part B: This will start after Part A, the purpose of Part B is to determine the optimal dose and schedule of the selected combination treatment from Part A. It is anticipated 60 participants will enrol in the Part A of the study. The study will consist of the following phases: - screening period (28 days) - treatment period at clinic & home (duration depends on how the cancer responds) - safety follow-up period (4 weeks after last dose) The study is sponsored by Merck GA