Distinct biosignatures associate with survival after chemoimmunotherapy in a randomized, three-arm phase II study in patients with metastatic pancreatic cancer.

• DOI: 10.1200/jco.2022.40.16_suppl.4010
• Publication Date: 2022-06-06T16:16:56Z
• Authors: Lacey J. Padrón; Deena M. Maurer; Mark H. O'Hara; Eileen Mary O'Reilly; Robert A. Wolff; Zev A. Wainberg; Andrew H. Ko; George A. Fisher; Osama E. Rahma; Jaclyn P. Lyman; Christopher R. Ca...; Jia Yu; Shannon M. Pfeiffer; Marko Spasic; Travis J Hollmann; Richard Chen; Jill O'Donnell-To...; Samantha Bucktrout; Theresa LaVallee; Robert H. Vonderh...
• Keywords: Chemoimmunotherapy; Clinical endpoint; Immune checkpoint

4010 Background: Preclinical and small clinical studies of chemoimmunotherapy for metastatic pancreatic ductal adenocarcinoma (mPDAC) point to a yet unrealized potential clinically significant immune activation. In our phase II study the CD40 agonist antibody sotigalimab (sotiga) and/or nivolumab (nivo) with gemcitabine nab-paclitaxel (chemo), we observed promising improvements in overall survival (OS) 105 patients newly diagnosed mPDAC (NCT03214250); primary endpoint 1-year OS rate was 57.7% (p = 0.006) nivo/chemo arm, 48.1% 0.062) sotiga/chemo arm 41.3% 0.233) nivo/sotiga/chemo (O’Hara, ASCO 2021) as compared historical control 35%. Here, report results multi-omic translational analyses designed identify signatures predictive benefit. Methods: Longitudinal blood tumor tissue samples were collected biomarker analysis. Tumor underwent RNA sequencing multiplex immunofluorescence (mIF). Peripheral analyzed by mass cytometry time flight (CyTOF), high parameter flow cytometry, proteomics. Machine learning (ML) algorithms applied data biosignatures related each arm. Results: Comprehensive multi-omic, multi-parameter identified distinct pretreatment longer specific or (Table, representative examples). Because received chemotherapy, these other arm-unique biomarkers suggest relationship immunotherapy rather than chemotherapy this randomized study. There evidence exhaustion sotiga/nivo/chemo that may explain lack Conclusions: From in-depth ML trial first-line patients, novel associated distinctly Clinical trials exploiting previously unappreciated aiming enrich response, are warranted further advance disease. information: NCT03214250. [Table: see text]