Trial reportJournal for immunotherapy of cancer2025
Immunological biomarkers of response and resistance to treatment with cabozantinib and nivolumab in recurrent endometrial cancer.
Trial report in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03367741 (A Randomized Phase 2 Study of Cabozantinib in Combination With Nivolumab in Advanced, Recurrent Metastatic Endometrial Cancer), which is not on this map. Cited by 10 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized Phase 2 Study of Cabozantinib in Combination With Nivolumab in Advanced, Recurrent Metastatic Endometrial Cancer
Who cites it
10 citing papers in PubMed.
- Multi-omics-driven precision medicine.iMeta · 2026Review
- Integrating artificial intelligence and multi-omics data for precision oncology in endometrial cancer: a narrative review.Functional & integrative genomics · 2026Review
- TAMs in the Gynecological Tumor Microenvironment: Insights from Cross-Cancer Studies for Immunotherapy.Cancers · 2026Review
- Humoral IgG1 responses to tumor antigens underpin clinical outcomes in immune checkpoint blockade.Nature medicine · 2026Article
- Multi-tyrosine kinase inhibitors: exploring immunomodulatory effects on various immune cell types in cancer.Cancer cell international · 2026Review
- Morin induces ferroptosis in endometrial cancer cells by down-regulating FTH1.Journal of molecular histology · 2026Article
- Case Report: Localized neutrophilic dermatosis at a split-skin donor site during PD-1 blockade: a unique immune-related adverse event.Frontiers in immunology · 2026Article
- Integrating multi-omics data to optimize immunotherapy in endometrial cancer: a comprehensive study.Discover oncology · 2025Article
- Biomarkers and immunotherapy in endometrial cancer: mechanisms and clinical applications.Frontiers in immunology · 2025Review
- Metabolic phenotypes: Molecular bridges between health homeostasis and disease imbalance.Computational and structural biotechnology journal · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors.
Funding
Abstract
backgroundAntiangiogenics combined with immune checkpoint blockade have become standard of care for recurrent endometrial cancer after standard platinum-based chemotherapy. To dissect mechanisms and define biomarkers associated with clinical outcomes to these combinations, we applied multidimensional immune monitoring to peripheral blood specimens collected from a randomized phase 2 trial of nivolumab with or without cabozantinib in 75 evaluable patients with recurrent endometrial cancer (NCI ETCTN 10104, NCT03367741). This trial demonstrated superiority of the combination to nivolumab alone. METHODS AND
resultsUsing Olink proteomics, mass cytometry, tumor antigen-specific ELISA, and whole exome tumor sequencing, we identified longitudinal immune signatures specific to cabozantinib use, including an increase in plasma HO-1 and reduction in plasma vascular endothelial growth factor receptor 2, interleukin-12, and circulating plasmacytoid dendritic cells. Prior exposure to immunotherapy and carcinosarcoma histology had no adverse impact on clinical benefit or biomarkers, and copy-number high tumors were associated with increased plasma granzymes on combination treatment. Higher baseline plasma levels of myeloid-related markers (chemokine ligand 23/CCL23, colony-stimulating factor-1/macrophage colony-stimulating factor/CSF1) were associated with poor overall and progression-free survival, and lack of clinical benefit (defined as progressive or stable disease <6 months) following combination treatment (Kaplan-Meier, multivariate Cox, false discover rate <0.05). Patients with favorable outcomes had higher levels of activated T-cell markers (plasma ICOS-L, CD28) and exhibited spontaneous autoantibody titers to tumor antigen NY-ESO-1. Patients experiencing severe adverse events from the combination therapy had higher baseline levels of neutrophil-derived markers (CXCL1).
conclusionsOverall, this study highlights potential resistance and response mechanisms to nivolumab+cabozantinib and suggests prioritizing combination treatment in patients with activated T-cell immunogenicity profiles while exploring future combinatorial therapies targeting myeloid populations to overcome resistance.
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.