Abstract 4951
Background
Despite multiple retrospective studies have demonstrated the clinical validity of molecularly-guided therapy selection in metastatic castrate-resistant prostate cancer (mCRPC), none have validated the actual clinical utility in the context of a randomised controlled trial. We hypothesise that treatment decisions based on plasma-derived cell-free DNA (cfDNA) profiling will increase progression-free survival (primary endpoint), which would result in prolonged overall survival and improved quality-of-life (secondary endpoints).
Trial design
The Prostate Biomarker (ProBio) trial is a recently-initiated adaptive, multi-arm, open-label, multiple assignment randomized controlled biomarker driven phase 3 trial in men with mCRPC. Men (n = 750) will be randomized to receive either standard of care or an experimental treatment with abiraterone acetate, enzalutamide, docetaxel, cabazitaxel, or carboplatin based on molecular biomarker signatures, as inferred from our liquid biopsy profiling. Therefor a prostate-specific1.48 Mb biomarker panel was designed and validated, which is capable of detecting 1) mutations in 78 genes, 2) genomic structural rearrangements in 11 prostate cancer-associated genes, 3) genome-wide copy number alterations, 4) 63 microsatellites to infer microsatellite instability, 4) tumour mutational burden and 5) estimate the circulating tumour DNA (ctDNA) fraction. The initial pre-defined biomarker signatures are defined as tumour properties or mutations in certain genes/pathways identified in the scientific literature as potentially important in prostate cancer treatment response encompassing the androgen receptor (AR), TP53, DNA-repair deficiency (DRD) and the TMPRSS2-ERG fusion. The statistical design of ProBio is novel, since the randomisation probabilities for a given experimental systemic therapy are subjective to change as the trial evolves and learns from prior experience. Secondly, ProBio implements a re-randomization of non-responding patients.
Clinical trial identification
2018-002350-78 (16/07/2018), NCT03903835 (29/03/2019).
Editorial acknowledgement
Legal entity responsible for the study
ProBio Investigators.
Funding
The Swedish Research Council, The Erling-Persson Family Foundation, The Swedish Cancer Foundation.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4543 - Long-term real-world (RW) outcomes in patients with advanced melanoma (MEL) treated with ipilimumab (IPI) and non-IPI therapies: IMAGE study
Presenter: Stéphane Dalle
Session: Poster Display session 3
Resources:
Abstract
4523 - Prognostic Factors for efficacy of Ipilimumab used after AntiPD1 and/or BRAF+MEK inhibitors in Melanoma Patients: an Italian Melanoma Intergroup study
Presenter: Riccardo Marconcini
Session: Poster Display session 3
Resources:
Abstract
3632 - Rechallenge with combination ipilimumab and anti-PD-1 (IPI+PD1) in metastatic melanoma after acquired resistance to IPI+PD1 immunotherapy
Presenter: Adriana Hepner
Session: Poster Display session 3
Resources:
Abstract
3732 - Clinicopathologic characteristics of immune colitis in melanoma patients treated with combination ipilimumab and anti-PD1 (IPI+PD1) and PD1 monotherapy.
Presenter: Kazi Nahar
Session: Poster Display session 3
Resources:
Abstract
5005 - Real-world outcomes of ipilimumab plus nivolumab for advanced melanoma in the Netherlands
Presenter: Michiel van Zeijl
Session: Poster Display session 3
Resources:
Abstract
5524 - Utilization of Real-World Data to Assess the Effectiveness of Immune Checkpoint Inhibitors (ICIs) in Elderly Patients with Metastatic Melanoma
Presenter: D Scott Ernst
Session: Poster Display session 3
Resources:
Abstract
5884 - Tumor mutational burden and response to PD-1 inhibitors: an analysis of 89 cases of metastatic melanoma.
Presenter: Léa Dousset
Session: Poster Display session 3
Resources:
Abstract
3120 - Increase in S100B and LDH as early outcome predictors for non-responsiveness to anti-PD-1 monotherapy in advanced melanoma.
Presenter: Elisa Rozeman
Session: Poster Display session 3
Resources:
Abstract
2157 - Immune status defined by molecular information layers predicts response to pembrolizumab treatment in advanced melanoma
Presenter: Guillermo Prado-Vázquez
Session: Poster Display session 3
Resources:
Abstract
2553 - Interim analysis of a phase Ib study of cobimetinib plus atezolizumab in patients with advanced BRAFV600 wild type melanoma progressing on prior anti-PD-L1 therapy
Presenter: Shahneen Sandhu
Session: Poster Display session 3
Resources:
Abstract