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

Inclusion criteria

• ✓. Histologically confirmed progressive or recurrent gynaecological carcinomas of the following histological subtypes:
• ✓. Histological tissue specimen (tissue block or 8-10 unstained slides) must be available (specimen can be the sample at diagnosis or taken at relapse). Otherwise, a biopsy must be carried out to obtain sufficient tissue for histological assessment
• ✓. Evidence of radiological disease progression since last systemic anti-cancer therapy and prior to trial entry
• ✓. Patients who have progressed after ≥1 prior platinum containing regimen. Platinum-based therapy does not need to be the last treatment prior to study entry. For Cohorts 1A, 1B, 2 and 3, patients who have disease progression within 6 months of last dose of a platinum-containing regimen, no more than two further lines of systemic therapy are permitted prior to trial entry
• ✓. Patients entering Cohorts 4 or 5 must have had prior anti-PD-1/anti-PD-L1/anti-CTLA-4 immunotherapy treatment, with a minimum duration of treatment is 6 weeks. Other previous immunotherapy treatments may be permissible following discussion with the Chief Investigator and ICR-CTSU. Patients who experienced toxicity leading to permanent discontinuation of prior immunotherapy are ineligible.
• ✓. Body weight \>30kg (Cohorts 4 and 5 only)
• ✓. Measurable disease by RECIST criteria v1.1, which can be accurately assessed at baseline by CT (or MRI where CT is contradicted or unclear). Patients with CA125 progression in the absence of measurable disease will NOT be eligible
• ✓. ECOG performance status 0 or 1 with no deterioration over the previous 2 weeks

Exclusion criteria