{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE316nnn/GSE316195/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE316195"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"A Phase 1 clinical trial and single-cell correlates of motixafortide, cemiplimab, gemcitabine and nab-paclitaxel for metastatic treatment-naïve metastatic pancreatic ductal adenocarcinoma.","description":"The C-X-C motif chemokine receptor 4 (CXCR4)/C-X-C motif chemokine ligand 12 (CXCL12) axis is a well-established contributor to the immunosuppressive and immune-excluded TME in pancreatic adenocarcinoma (PDA). Building on pre-clinical data demonstrating a survival benefit with the addition of gemcitabine to CXCR4 and PD1 inhibition in the KPC mouse model, we conducted an open-label, single-arm phase 1 clinical trial combining CXCR4 inhibition (motixafortide), PD-1 blockade (cemiplimab), and chemotherapy (gemcitabine/nab-paclitaxel; MCGN) in treatment-naïve patients with metastatic PDA (n=11). MCGN was safe and tolerable, achieving a 64% partial response (PR) by iRECIST, a 55% confirmed partial response (cPR), and a 91% disease control rate (DCR). The median PFS and OS were 9.7 months (95% confidence interval [CI]: 5.9-not reached [NR]) and 10.1 months (95% CI: 9.3-NR), respectively. One patient achieved a pathological complete response within the primary tumor and the hepatic metastasis after undergoing a pancreatoduodenectomy and hepatectomy and has remained free of disease for 18 months, suggesting that durable responses are possible with MCGN treatment. Single-nucleus RNA-sequencing of serial tissue biopsies from all trial participants revealed a reduction in transcriptional heterogeneity and depletion of cells expressing epithelial-to-mesenchymal transition states, while treatment-resistant tumors maintained tumor heterogeneity. The presence of CXCL12+ proaxogenic Cancer Associated Fibroblasts (pCAFs) were predictive of MCGN efficacy and depleted in resistant samples, suggesting that they represent the substrate for treatment response. MCGN also induced a highly inflamed tumor-microenvironment, which we confirmed with serial tissue staining, and rescue of T cell dysfunction. Based on these promising data and biomarkers, we have launched a multicenter randomized phase 2 trial comparing MGCN to GN in patients with treatment-naïve metastatic PDA (NCT04543071), which is ongoing.","dates":{"publication":"2026/07/13"},"accession":"GSE316195","cross_references":{"GSM":["GSM9447229","GSM9447249","GSM9447238","GSM9447228","GSM9447239","GSM9447236","GSM9447247","GSM9447237","GSM9447248","GSM9447234","GSM9447245","GSM9447246","GSM9447235","GSM9447243","GSM9447232","GSM9447233","GSM9447244","GSM9447241","GSM9447230","GSM9447231","GSM9447242","GSM9447240"],"GPL":["24676"],"GSE":["316195"],"taxon":["Homo sapiens"]}}