ATr Inhibitor in Combination With Olaparib/Durvalumab (MEDI4736) in Gynaecological Cancers With ARId1A Loss or no Loss

ATARI is a multi-centre, open-label, multiple two-stage parallel cohorts phase II clinical trial for patients with relapsed gynaecological cancers, with ARID1A-deficient ('loss') and "no loss." The trial tests the ATR inhibitor drug ceralasertib (AZD6738) alone and in combination with either a PARP inhibitor drug called olaparib, or an anti-PD-L1 immunotherapy called durvalumab (MEDI4736) to assess the response in groups of patients selected based on their cancer cell subtype and the presence of an abnormality in ARID1A. The treatment groups are: 1A - Women with clear cell subtype with (ovarian/uterus) ARID1A loss treated with ceralasertib. 1B - Women with clear cell subtype with (ovarian/uterus) ARID1A loss treated with ceralasertib and olaparib. 2 - Women with clear cell subtype (ovarian/uterus) with no ARID1A loss treated with AZD6738 and olaparib. 3 - Women with other rare gynaecological cancers (carcinosarcoma, cervical, endometrioid type) irrespective of ARID1A loss treated with ceralasertib and olaparib. 4 - Women with endometrial cancers (serous, clear cell, endometroid, carcinosarcoma) with ARID1A loss treated with ceralasertib and durvalumab. 5 - Women with endometrial cancers (serous, clear cell, endometroid, carcinosarcoma) with no ARID1A loss treated with ceralasertib and durvalumab.