Neo-adjuvant Chemotherapy Combined With Stereotactic Body Radiotherapy to the Primary Tumour +/- Durvalumab, +/- Oleclumab in Luminal B Breast Cancer:

This trial consists of a safety run-in followed by a phase II randomised trial. The goal of the safety run-in is to assess the safety of adding SBRT to the neo-adjuvant systemic treatment. The doses of the IMPs will be identical in the safety run-in and the phase II randomised trial. Individual subject timelines are also identical in the safety run-in and the phase II randomised trial.

The safety run-in is done as a precursor to the phase II randomised part of the Neo-CheckRay trial. Six subjects will be included in the safety run-in. These subjects are not part of the phase II total recruitment.

Subjects in the safety run-in will receive the following treatments corresponding to arm 3 of the phase II randomised trial. This consists of:

* q1w paclitaxel 80 mg/m² IV for 12 administration (12 weeks) followed by q2w dose-dense doxorubicin-cyclophosphamide IV (60 mg/m² and 600 mg/m² respectively) for 4 administrations (8 weeks) * Anti-PD-L1 antibody durvalumab 1500 mg IV q4w for 5 administration (20 weeks) * Anti-CD73 antibody oleclumab 3000 mg IV q2w for 4 administrations (8 weeks), followed by q4w for 3 administrations (12 weeks) * Pre-operative radiation therapy (boost dose) 3x8 Gy on the primary tumour at week 5

If all requirements are meet during the safety run-in, then the phase II part of the study will be opened. The phase II will consist of luminal B breast cancer subjects candidate for neo-adjuvant chemotherapy will be randomised in a 1:1:1 ratio between 3 arms:

1. Arm 1: the combination of weekly paclitaxel 80 mg/m² IV followed by q2w dose- dense doxorubicin-cyclophosphamide (ddAC) (60 mg/m² doxorubicin IV and 600 mg/m² cyclophosphamide IV) and pre-operative radiation therapy on the primary tumour (3x8 Gy). 2. Arm 2: drugs regimen of Arm 1 with the addition of the anti-PD-L1 antibody durvalumab IV 1500 mg q4w. 3. Arm 3: drugs regimen of Arm 2 with the addition of the anti-CD73 antibody oleclumab IV 3000 mg q2w for 4 administrations, followed by q4w for 3 administrations.

The primary tumour will be excised 2-6 weeks after completion of ddAC. The study treatments end at surgery. All treatment after surgery, such as post-operative radiotherapy and hormonal therapy, will be performed according to standard of care and local site guidelines. The patient will then be followed for the next 5 years.