Phase 2 Study of Neoadjuvant PEMbrolizumab Before Radical PROstatectomy in High-risk Prostate Cancer Patients

This is a phase 2, open-label, non-randomized, single-arm study in patients with high-risk PCa diagnosed with prostate biopsy and undergoing RP and ePLND. Screening assessments should be performed no more than 3 weeks prior to the start of study treatment. Local, nodal and systemic staging with prostate mpMRI, abdominal and chest CT, PSMA-PET/CT and bone scans will be performed before the administration of pembrolizumab. Pembrolizumab will be administered at the dose of 200 mg intravenously, every 3 weeks, for a total of 3 cycles prior to RP and ePLND. Following the screening assessment, subsequent assessments will be carried out after the 3 administrations of the study drug prior to RP and ePLND. If an unscheduled assessment is performed and the patient has not progressed, the results should be reported at the next scheduled visit. After the last cycle of pembrolizumab, mpMRI and PSMA-PET/CT scan will be performed to re-stage the tumour. Progressive disease will be defined as an increase of 20% in the maximum diameter of the index lesion at multiparametric MRI or as the onset of nodal or distant metastases at imaging or onset of symptoms and skeletal related events. In the case of symptomatic disease progression (i.e., de novo onset of symptomatic distant metastases), the patient will not complete the 3 cycles of pembrolizumab and will be considered for immediate imaging (i.e., bone scan, mpMRI and PSMA-PET/CT scan) to re-stage the tumour and for treatment according to clinical guidelines. After RP, patients will be managed according to clinical guidelines. PDL-1 status will be assessed on all samples of patients enrolled on the study. Tissue and blood samples will be collected before and after the administration of pembrolizumab. The presence of biomarkers predictive of radiological and pathological response to neoadjuvant administration of pembrolizumab will be assessed. Patients will be monitored carefully for the development of adverse events and will be monitored for clinical evidence of disease progression according to usual standards of clinical practice. Adverse events will be evaluated according to criteria outlined in the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. There will be no intrapatient dose escalation in this study. For individual patients that experience dose-limiting toxicities, no criteria for dose modification of pembrolizumab will be applied, but only criteria for dose delays as detailed in the protocol. Patients will be treated with a maximum of 3 cycles of therapy until surgery (i.e. RP and ePLND), provided that no dose-limiting toxicities will occur throughout the treatment course for each individual patient.