Biomarkers for Neoadjuvant Pembrolizumab in Non-Metastatic Prostate Cancer Positive by 18FDG-PET Scanning

Official Title

Phase II Clinical and Translational Study of Neoadjuvant Pembrolizumab Before Radical Prostatectomy in Non-metastatic Gleason ≥8 Prostate Cancer Patients Positive by 18FDG-PET Scanning ( PICT-01)

Summary:

Various approaches are currently being developed for prostate cancer immunotherapy. However, a major challenge facing the development of cancer immunotherapy is the identification of tumours that would best respond to this type of treatment. Different studies suggest that prostate cancer more likely to progress are more infiltrated by exhausted T cells expressing the cell surface protein PD1 (Programmed cell death 1). Therefore, there is a strong rationale for selecting patients at higher risk of progression for testing the efficacy of anti-PD1 therapy. High glucose metabolism as detected by fludeoxyglucose F18 (FDG)-positron emission tomography (PET) (18FDG-PET) imagery is an innovative biological biomarker-based method to identify patients at higher risk of recurrence and early failure to hormonotherapy. Recent study demonstrated that high intra-prostatic 18-FDG-uptake was associated with higher Gleason grades. Therefore the one third of Gleason ≥ 8 prostate cancer patients with higher 18FDG uptake would be ideal candidates for early immunotherapy treatments based on anti-PD-1 such as pembrolizumab. The study aimed to identify biomarkers predictive the response to Pembrolizumab given prior to radical prostatectomy in participants with primary prostate cancer at high risk of progression.

Trial Description

Primary Outcome:

• The antitumour activity of pembrolizumab assessed as the tumour response rate based on the change in tumour volume as measured by 18FDG-PET
• Mean difference change in proliferative index in prostate cancer patients between patients treated with pembrolizumab and the control cohort
• Immune cell infiltration and immune checkpoint expression

Secondary Outcome:

• One year PSA (Prostate Specific Antigen) failure rate
• Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.0
• Number of participants with decrease in SUV uptake after 3 cycles of pembrolizumab
• Assess a possible correlation between deficient mismatched repair (dMMR) and microsatellite instability-high (MSI-H) and response to pembrolizumab.
• Assess the expression of a series of cytokines and eicosanoids

This is a Phase II, single-arm and open-label trial of pembrolizumab (MK-3475) in localized prostate cancer patients with newly diagnosed non-metastatic prostate cancer (Gleason grade ≥8 on biopsy) with positive tumour by FDG-PET (SUV max >4) who chose to undergo radical prostatectomy and lymph node dissection as primary treatment. The trial will meet its endpoint if a reduction in cancer extent, proliferative index and increased apoptosis, as well as an induction of favourable immune cell infiltration and immune checkpoint expression profiles are observed after treatment compare to baseline..

View this trial on ClinicalTrials.gov