Abstract 642TiP
Background
Immune checkpoint blockade (ICB) benefits a limited number of unselected patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Only 3-5% of pts with high tumour mutational burden (hTMB)/ or microsatellite instable (MSI) currently have approval for treatment with anti-PD1 ICB. More pts may benefit, particular those with DNA damage repair alterations. Also, higher responses are witnessed with combinatory nivolumab 1mg/kg (NIVO-1) with ipilimumab 3mg/kg (IPI-3). NIVO-1/IPI-3 showed substantial grade 3-4 toxicity, limiting applicability of this regimen in mCRPC. The aim of this study is to investigate the efficacy and safety of a new treatment regimen of NIVO and IPI, in a molecular-selected population.
Trial design
A total of 75 biomarker-selected mCRPC pts are to be included in this open-label non-randomized phase II trial. Inclusion started on 19 January 2021. Selection criteria are a homologous recombination deficiency or BRCA2 inactivation, MSI or mismatch repair deficiency, a hTMB and a tandem duplication signature or CDK12 inactivation. Other key inclusion criteria are ECOG 0-1 and measurable disease per RECIST1.1. The study has two cohorts, of which main cohort 1 (n=50) will assess efficacy in pts naïve for ICB, and an exploratory cohort 2 (n=25). Pts will be treated with NIVO-3 and IPI-1 for 4 Q3W cycles, followed by NIVO 480mg Q4W up to one year. Efficacy will be assessed by a disease control rate (DCR) lasting at least 6 months. Safety data will comprise all-grade treatment-emergent adverse events (TEAEs) in 75 pts. Key secondary endpoints are best ORR per RECIST 1.1. criteria, biochemical response rate per PCWG3 criteria, and radiographic progression-free survival per irRECIST. Translational objectives are aimed to optimize and validate predictive signatures from tissue and liquid biopsies. The trial will require a baseline and an on-trial tissue biopsy. Exploratory objectives will include in-depth genomic and transcriptomic assessment, multispectral immunohistochemical analyses of immune infiltrate, circulating tumour DNA and T-cell receptor repertoire analyses.
Clinical trial identification
NCT04717154.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
BMS.
Disclosure
All authors have declared no conflicts of interest.