Nature communications · 2026
Motixafortide, cemiplimab, gemcitabine and nab-paclitaxel in metastatic pancreatic cancer: a single-arm phase 2 study with single-cell correlatives.
СтатьяКлиническое исследование II фазыНазвание и аннотация: Перевод в очереди
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Raufi Alexander G, D'Souza Edridge K, May Michael S, Sedycias Sarah, Pellicciotta Ilenia, Pan Samuel, Wang Shikun, Palermo Carmine, Sastra Steven, Sender Naomi, Ross Isabelle, Li Li, Luthria Karan, Shah Parin, Tagore Somnath, Walsh Zachary H, Turk Andrew, Sema Bircan, Iuga Alina, Dajiang Sun, Kluger Michael D, Schrope Beth A, Brown Dane, Fojo Tito, Schvartzman Juan-Manuel, Pumpalova Yoanna, Moy Ryan H, Bates Susan, Wu Linda, Hibshoosh Hanina, Tan Aik Choon, Schwartz Gary K, Chabot John A, Olive Kenneth P, Izar Benjamin, Manji Gulam A
Аннотация
The C-X-C motif chemokine receptor 4 (CXCR4)/C-X-C motif chemokine ligand 12 (CXCL12) axis drives immune exclusion in pancreatic ductal adenocarcinoma (PDA). Building on our preclinical data, we conducted the first stage of an open-label, single-arm phase 2 clinical trial combining CXCR4 inhibition (motixafortide), PD-1 blockade (cemiplimab), and chemotherapy (gemcitabine/nab-paclitaxel [GN]; MCGN) in 11 treatment-naïve patients with metastatic PDA ( NCT04543071 ). The primary endpoint, objective response rate, was 64% partial response and 55% confirmed partial response per Response Evaluation Criteria in Solid Tumors. Secondary endpoints include median progression-free survival of 9.7 months (95% confidence interval [CI]: 5.9-not reached [NR]), overall survival of 10.1 months (95% CI: 9.3-NR), duration of response of 8.2 months, and 91% disease control rate. One patient achieved a pathological complete response after pancreatoduodenectomy and hepatectomy, remaining disease-free for 18 months without adjuvant therapy. Exploratory single-nucleus RNA-sequencing of serial biopsies showed reduced tumor heterogeneity, depletion of epithelial-to-mesenchymal transitional states, and enrichment of CXCL12+ cancer-associated fibroblasts in responders relative to resistant patients. MCGN also induced tumor inflammation as confirmed by tissue staining and T cell rescue. A multicenter randomized phase 2 trial comparing MCGN to GN in patients with treatment-naïve metastatic PDA is ongoing.