Funding restrictions

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

Inclusion Criteria:

1. Willing and able to provide written informed consent
2. Ability to comply with the protocol
3. Female ≥ 18 years of age
4. Histologically confirmed metastatic or locally advanced breast cancer that is Luminal B, ER+ve, HER2-ve.
5. Patients must have measurable disease.
6. Representative formalin-fixed paraffin embedded breast tumour samples from the primary or recurrent cancer.
7. ECOG performance status 0-1
8. Adequate haematologic and end-organ function within 28 days prior to the first study treatment
9. Patients of childbearing potential are eligible provided they have a negative serum or urine pregnancy test on Day 1 Cycle 1 (within 72 hours) of study treatment, preferably as close to the first dose as possible.

Exclusion Criteria:

1. Luminal A breast cancer
2. Prior chemotherapy for advanced or metastatic disease
3. Prior treatment with paclitaxel in the (neo)adjuvant setting within 12 months from the end of paclitaxel treatment and randomisation into this study
4. Patients with neuropathy ≥ Grade 2
5. Previous systemic treatment for other neoplasms within 5 years prior to randomisation.
6. Patients with prior allogeneic stem cell or solid organ transplantation.
7. Prior treatment with CD137 agonists, AKT inhibitors, anti-CTLA-4, anti-OX-40, anti-programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents.
8. Patients must not have a diagnosis of immunodeficiency or receiving chronic systemic steroid therapy.
9. Received therapeutic oral or intravenous antibiotics within 14 days prior to randomisation.
10. Administration of a live vaccine within 30 days prior to the first dose of study drug.
11. Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL] -2) within 28days or five half-lives of the drug, whichever is shorter, prior to randomisation.
12. History of autoimmune disease.
13. History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia requiring steroids, or evidence of active pneumonitis on screening chest CT scan.
14. Active infection requiring systemic therapy.
15. History of HIV infection
16. Known active hepatitis infection.
17. Known history of active tuberculosis