Phase II clinical and translational study of neoadjuvant pembrolizumab for personalization of prostate cancer treatment

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Challenge: Cancer therapy has been transformed in recent years by the impressive success of immunotherapy using immune checkpoint inhibitors. However, the success of immunotherapy in some types of cancers, including prostate cancer (PCa), has been rather limited. A major challenge facing the development of PCa immunotherapy is the identification of tumors that would best respond to this type of treatment. Current evidences suggest that the subset of prostate tumors at higher risk of recurrence and progression might be more responsive to immune checkpoint inhibitors.

Solution: High glucose metabolism as detected by PET/CT imagery is an innovative biological biomarker-based method to identify patients at higher risk of recurrence and early failure to the standard treatment of androgen deprivation therapy which goal is to prevent the cancer cells from growing. The team thus hypothesize that patients with high glucose metabolism PCa have very aggressive tumors more likely to have higher genomic instability, abnormal DNA mismatch repair machinery and to have induced a blocked immune response. As is the case for other cancers with high glucose metabolism such as melanoma, bladder and lung cancers, this subgroup of PCa may be more responsive to pembrolizumab (PD-1 inhibitor) treatment, particularly at an early stage, untreated by androgen deprivation therapy. Moreover, these patients represent a population likely to fail primary treatment and develop rapid resistance to androgen deprivation therapy thus justifying novel experimental approaches.

Expected achievements/Impact : In this project, a clinical trial will be performed to test the effect of 3 cycles of pembrolizumab given prior to radical prostatectomy (RP) in 30 patients that are positive high glucose metabolism. The safety, tolerability and clinical efficacy of this treatment will be determined and biomarkers of therapy response such as cytokines, eicosanoids, mismatch repair deficiency, microsatellite instability and new genomic biomarkers will be identified.

Principal Investigators:
Yves Fradet
Frédéric Pouliot
CHU de Québec-Université Laval
Co-Investigators:
Jean-Mathieu Beauregard
Alain Bergeron
Vincent Fradet
Arnaud Droit
CHU de Québec-Université Laval
Ongoing Project
$ 1,421,201/ 3 years
Supported by CQDM through:
– Merck
– MEI 
And by co-funding partner :
– Fondation du CHU de Québec
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