Investigating the impact of adding olaparib, or olaparib and durvalumab together, to standard chemotherapy before surgery in young, pre-menopausal women with HER2-negative breast cancer.

INTERVENTION: Study treatment is for 12 weeks. Arm A: Olaparib: 100 mg tablet taken twice daily for weeks 1‐12 with weekly paclitaxel intravenously (IV) 80 mg/m^2 for 12 weeks Arm B: Olaparib: 100 mg tablet taken twice daily for weeks 1‐12; and Durvalumab: 1500 mg intravenously (IV) every 4 weeks for 12 weeks (i.e. 3 treatments) with weekly paclitaxel intravenously (IV) 80 mg/m^2 for 12 weeks. Olaparib tablets can be taken by participants at home. Olaparib should be taken twice daily, at approximately the same times each day (approximately 12 hours apart), with one glass of water. Olaparib tablets should be swallowed whole and not chewed, crushed, dissolved or divided. Participants will be provided with a diary to record when they take olaparib tablets and the diary will be checked at each clinic visit. Durvalumab and paclitaxel will be administered at study/clinic visits by hospital/clinic staff as according to institution guidelines. Durvalumab is administered before administration of paclitaxel. On days on which all three drugs are given, olaparib is taken first followed by durvalumab, followed by paclitaxel. Durvalumab may be administered any time after taking olaparib. Paclitaxel can be delivered after durvalumab if no infusion related symptoms are observed during the durvalumab infusion. Infusions of durvalumab and paclitaxel are administered by clinic/hospital staff according to institutional guidelines. CONDITION: Breast Cancer; ; Breast Cancer Cancer ‐ Breast PRIMARY OUTCOME: The pathologic complete response (pCR) rate in each arm. pCR is defined as ypT0/is ypN0 assessed by examination of tissue (breast and nodes) removed at surgery.[At the time of definitive surgery] SECONDARY OUTCOME: Event free survival (EFS) in Treatment Arm A and Treatment Arm B.[The length of time from randomisation until the first evidence of disease progression (loco‐regional or distant) or date of death due to any cause, assessed for up to 5 years post‐surgery.] Overall survival (OS) in Treatment Arm A and Treatment Arm B.[The length of time from randomisation until the date of death from any cause, assessed for up to 5 years post‐surgery.] Safety in Treatment Arm A and Treatment Arm B assessed as laboratory abnormalities, worst grade of adverse events (AEs) and serious adverse events (SAEs) documented using NCI CTCAE v5.0. ; ; Adverse events will be assessed by clinical examination and participant self‐report and described by: ; 1) NCI‐CTCAE V5.0 terms – Common Terminology Criteria for Adverse Events; ; 2) Duration (start and end dates); ; 3) Severity Grade; ; 4) Relationship to study treatment (suspected/not suspected); ; 5) Action taken with regard to study treatment (e.g. omitted, discontinued); ; 6) Whether the event was reported as a Serious Adverse Event (SAE). ; ; For potential Adverse Events for OLIO, please see list of side effects (Cancer Fields).[Frequency of adverse events assessed throughout the study up to 90 days after the last dose of study treatment.] The Residual Cancer Burden (RCB) rate (class 0 or 1) in Treatment Arm A and Treatment Arm B.[At the time of definitive surgery.] INCLUSION CRITERIA: PRE‐SCREENING: For inclusion in pre‐screening for the study, participants must fulfil all the following criteria: 1. Has provided written, informed consent to participate in pre‐screening for the study. 2. Female aged >= 18 to <= 44 years at the time of breast cancer diagnosis. 3. Premenopausal as defined as the presence of at least one ovary at the time of diagnosis of breast cancer. 4. Histologically confirmed ER‐positive and HER2‐negative early breast cancer by local assessment: a) ER‐positive is defined as >= 1% of tumour nuclei positive for ER via IHC analysis [CAP Guidelines 2020] b) HER2‐negative is defined as a negative ISH test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative ISH result is also required [CAP Guidelines 2018] c) PR may be positive or negative. 5. High disease burden defined as either: a) cT1c‐T2, cN1‐cN3 OR b) cT3‐T4, cN0‐cN3. Note: multicentric tumours are allowed with at least 1