NEOPRISM-CRC: Neoadjuvant pembrolizumab stratified to tumour mutation burden for high risk stage 2 or stage 3 deficient-MMR/MSI-high colorectal cancer.

作者：Kai‐Keen Shiu, Yanrong Jiang, Mark Saunders, Jenny F. Seligmann, Timothy Iveson, Richard H. Wilson, Janet Graham, Khurum Khan, Anna-Maria Militello, Sandra Irvine, Temi Adedoyin, Rubina Begum, Reshma Bhat, William Wilson, Andrew Plumb, Austin Obichere, Manuel Rodriguez‐Justo, Marnix Jansen · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco.2024.42.17_suppl.lba3504 · 被引用次数：35 · 研究领域：Colorectal Cancer Treatments and Studies、Cancer Immunotherapy and Biomarkers、Genetic factors in colorectal cancer

LBA3504 Background: The prognostic advantage of early stage deficient-MMR/MSI-High colorectal cancer (CRC) is lost after relapse. Hence, there is a clinical imperative to maximise the chance of cure in early-stage disease. Tumour mutation burden (TMB) is an emerging biomarker for response and clinical benefit to immunotherapy in the advanced setting. NEOPRISM-CRC (Neoadjuvant PembRolizumab In Stratified Medicine – ColoReCtal) is the first multicentre Phase II Trial to determine if neoadjuvant pembrolizumab is efficacious and safe, prospectively stratified to TMB. Methods: The trial population included patients (pts) with operable high-risk stage 2 or stage 3 dMMR/MSI-High CRC. Pts with tumours that were TMB high or medium (≥6 mutations/Mb on FoundationOneCDx test) received 3 cycles of pembrolizumab (200mg every 3 weeks) and underwent surgery within 4-6 weeks of last cycle. Pts with TMB low tumours (≤5 mutations/Mb) underwent surgery 4-6 weeks after 1 cycle of pembrolizumab. The primary end point was pathological complete response rate (pCR). Secondary endpoints included 3-year relapse free survival, overall survival, safety, and health-related quality of life. The trial also incorporated translational endpoints to explore relationships between possible predictive novel biomarkers and response to pembrolizumab in blood, tumour tissue and microbiome. We required 19 pts with TMB high or medium tumours to detect a pCR after 3 cycles of neoadjuvant pembrolizumab of 33% (minimum of...