MAESTRO/PERSEUS: A phase II molecular stratification/treatment platform in Metastatic Castration Resistant Prostate Cancer (mCRPC) – PERSEUS1 (pembrolizumab; NCT03506997)
Session type: Poster / e-Poster / Silent Theatre session
Prostate cancer (PC) comprises many highly heterogeneous genomic sub-types with patients responding differently to various treatments, with variable clinical outcomes. Elucidation of the molecular landscape of mCRPC suggests that the majority of patients harbour potentially actionable mutations, many of which are uncommon. Investigating new targeted agents in unselected patients has a high risk of failure. We envision the future of mCRPC drug development will be based on molecular stratification, and hypothesize that sensitivity to immune checkpoint inhibitors (ICI) in PC, correlates with a number of key variables related to DNA repair defects, including DNA repair defects, and neoantigen burden generated from tumour genomic aberrations that can also increase tumour-infiltrating lymphocyte counts.
PERSEUS1, the first of a number of planned phase II trial cohorts, will recruit patients molecularly profiled under the MAESTRO screening protocol. It has a multi-stage single-arm Simon Minimax design (p0=0.20; p1=0.40; α=0.05; β=0.1). The primary objective is to determine the anti-tumour activity of the ICI pembrolizumab (200mg IV 3-weekly) in mCRPC patients progressing on standard treatments deemed to have a high likelihood of ICI sensitivity based on a composite assay utilizing next generation sequencing and multiplex immunocytochemistry. Part A will recruit 45 patients; 24 in stage 1, 21 in stage 2. The primary endpoint is tumour response. Ineffectiveness will be concluded if ≤5 and ≤13 responses are seen in stage 1 or 2 respectively. If >13 responses are reported a subsequent (biomarker-enriched) cohort will be pursued. Patients receiving clinical benefit, free from intolerable toxicity, may continue on pembrolizumab for up to 2-years or until disease progression. PERSEUS1 recruitment opened in November 2018 and 7 of 45 patients have been enrolled to 31st May 2019.