PELICAN is a randomised phase II trial that aims to evaluate the efficacy and safety of paclitaxel plus pembrolizumab relative to paclitaxel alone, in patients with locally advanced or metastatic ER-positive, HER2-negative, Luminal B breast cancer who have received no prior chemotherapy for advanced or metastatic disease.~Luminal B is defined as high Ki67 (≥20%) and /or histological grade 3 and / or Luminal B according to PAM50 assay. This study will include patients irrespective of PD-L1 expression, but patients will be stratified by centrally determined PD-L1 expression. The number of patients with PD-L1 negative tumours (<1% expression) will be capped at 50% of the total study population.~Patients will be randomised (2:1) to one of the two treatment arms:~Pembrolizumab every 3 weeks (Q3W) plus Paclitaxel on Days 1,8, and 15 every 28 days~Paclitaxel on Days 1,8, and 15 every 28 days Paclitaxel alone~Randomisation will be stratified by the following two factors:~Centrally assessed PD-L1 expression (<1% PD-L1 expression; ≥1%)~Presence vs non-presence of visceral metastases~Paclitaxel treatment will be continued for at least 6 cycles unless there is evidence of unacceptable toxicity, disease progression, or if the patient requests to stop the treatment. If paclitaxel treatment is discontinued prior to disease progression, patients in the combination arm should continue pembrolizumab single agent therapy until progression or evidence of unacceptable toxicity up to a maximum of 2 years.~If disease progression is documented (RECIST 1.1) while the patient is on study medication (in the pembrolizumab plus paclitaxel arm) it would be standard practice for the patient to be taken off study medication. However, in the absence of other discontinuation criteria, patients treated with paclitaxel plus pembrolizumab may be continued on study medication if in the opinion of the treating physician there is clinical benefit. In this case patients must meet all of the following criteria:~Evidence of clinical benefit as assessed by the investigator~Absence of symptoms and signs (including worsening of laboratory values [e.g., new or worsening hypercalcemia]) indicating clinically significant progression of disease~No decline in Eastern Cooperative Oncology Group (ECOG) performance status that can be attributed to disease progression~Absence of tumour progression at critical anatomical sites (e.g., leptomeningeal disease) that cannot be managed by protocol-allowed medical interventions (i.e., pain secondary to disease or unmanageable ascites, etc.), as determined by the investigator after an integrated assessment of radiographic data, biopsy results (if available), and clinical status.~Pembrolizumab treatment will not exceed 2 years.~Patients who were randomized to the paclitaxel alone must discontinue study treatment upon determination of progressive disease. No crossover is allowed. On completion of study treatment in both arms, patients will enter a survival follow-up period during which data on cancer therapy, disease status and survival status will be collected. Endocrine maintenance therapy is not permitted prior to disease progression.
PELICAN is a randomised phase II trial that aims to evaluate the efficacy and safety of paclitaxel plus pembrolizumab relative to paclitaxel alone, in patients with locally advanced or metastatic ER-positive, HER2-negative, Luminal B breast cancer who have received no prior chemotherapy for advanced or metastatic disease.~Patients will be randomised (2:1) to one of the two treatment arms:~Pembrolizumab plus Paclitaxel~Paclitaxel