Paclitaxel + Carboplatin + Durvalumab With or Without Oleclumab for Previously Untreated Locally Recurrent Inoperable or Metastatic TNBC

The trial consists of two parts: PHASE I Part 1 is a phase I trial examining the combination of paclitaxel, carboplatin, durvalumab and oleclumab in order to define the recommended phase II dose (RP2D) of oleclumab in this treatment combination. The period for DLT evaluation is defined as the time from receiving the first dose of oleclumab until the planned administration of the third dose; this corresponds to 28 days after receiving the first dose of oleclumab in case no treatment interruption occured. Patients who develop a DLT will stop study treatment permanently. PHASE II Part 2 is a multicenter, randomized, open-label trial investigating the role of an anti-CD73 monoclonal antibody (oleclumab) in combination with an anti-PD-L1 antibody (durvalumab) plus chemotherapy (paclitaxel + carboplatin) as first-line treatment for locally recurrent inoperable or metastatic TNBC. Patients will be randomized between chemotherapy (paclitaxel and carboplatin) with immunotherapy including durvalumab with or without oleclumab (1:1 ratio). PHASE I and PHASE II Paclitaxel and carboplatin will be given weekly for a total of 12 injections. Immunotherapy (durvalumab with or without oleclumab) will be given as long as the patient benefits. Premature discontinuation of paclitaxel/carboplatin or discontinuation of durvalumab/oleclumab is indicated in case of: * Progressive disease (PD) using RECIST v1.1 criteria or iRECIST assessed locally * Unacceptable toxicity * Intercurrent illness that necessitates discontinuation of study treatment * Investigator's decision to withdraw the subject * Pregnancy * Subject noncompliance with the study treatment or procedure requirements * Withdrawal of consent to treatment * Death * Administrative reasons requiring cessation of study treatment. Initial disease status will be evaluated by imaging studies (contrast-enhanced CT scan of the chest, the abdomen and the pelvis or MRI of the chest, the abdomen and the pelvis) during the screening phase. Disease status will be followed by imaging studies at weeks 8 (± 3 days), 16 (± 3 days) and 24 (± 3 days) post start of treatment (allowing efficacy data to be captured as close to 24 weeks post start of study treatment as possible for a more accurate evaluation of DCR). Thereafter imaging will continue every 12 weeks (± 3 days; contrast-enhanced CT scan or MRI) independent of any treatment delays. Patients who stopped all study treatments for reasons other than PD will continue post-treatment imaging studies for disease status follow-up as described in the schedule of assessment until verified PD, start of a new anti-cancer treatment, withdrawal of consent to study participation, death, or end of the study whichever comes first. Note: Pseudo-progression related to immunotherapy: Patients experiencing PD as defined by RECIST v1.1 can continue the study treatment in case of good clinical condition assessed by a stable or even improved ECOG performance status. If the next assessment of tumour burden (8 weeks later) confirms PD (as defined by iRECIST) study treatment must be discontinued. Unconfirmed PD as defined by iRECIST (iUPD) can only be assigned for the first 2 imaging assessments (week 8 and week 16) and several times as long as confirmed progression (iCPD) is not confirmed at the next assessment. If PD is not confirmed, reassessments continue as originally planned.