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
2115 - Preclinical in vivo screening to predict responder patients depend on EGFR status
Presenter: Yejin Kim
Session: Poster Display session 3
Resources:
Abstract
3349 - Interplay between miR-17-5p and MALAT-1 Shapes The Cytokine Storm in Triple Negative Breast Cancer (TNBC) Tumor Microenvironment
Presenter: Raghda Soliman
Session: Poster Display session 3
Resources:
Abstract
4014 - Clinical verification on the relationship between lipid metabolism and the immune microenvironment of breast cancer
Presenter: Wataru Goto
Session: Poster Display session 3
Resources:
Abstract
4158 - The clinical and transcriptional signatures of human CD204 reveal an applicable marker for tumor associated macrophage in breast cancer
Presenter: Yunjie He
Session: Poster Display session 3
Resources:
Abstract
5392 - Activated effector T cells co-expressing multiple inhibitory receptors (IRs) are enriched in the tumor immune microenvironment in high grade serous ovarian cancer (HGSOC)
Presenter: Alice Bergamini
Session: Poster Display session 3
Resources:
Abstract
2617 - Oncolytic reovirus as a new anti-tumor strategy in castration resistant prostate cancer
Presenter: Yunlim Kim
Session: Poster Display session 3
Resources:
Abstract
2995 - Dysregulation of helper T lymphocytes in esophageal squamous cell carcinoma (ESCC) patients is highly associated with aberrant production of miR-21
Presenter: Ali Memarian
Session: Poster Display session 3
Resources:
Abstract
3597 - Myeloid derived suppressor cells but not regulatory T cells are associated with adaptive immunity and clinical outcomes in anal squamous cell carcinoma
Presenter: Christophe Borg
Session: Poster Display session 3
Resources:
Abstract
3430 - Evaluation of immune responses among responders (R) and non-responders (non-R) in a humanized mouse model with colorectal cancer (CRC) xenografts treated with combination immunotherapy
Presenter: Juan Marín Jiménez
Session: Poster Display session 3
Resources:
Abstract
1995 - ¬¬Advanced melanoma patients with high CD16+ macrophages have better response and survival to anti-PD-1 based immunotherapy
Presenter: Hansol Lee
Session: Poster Display session 3
Resources:
Abstract