ArticleFrontiers in immunology2022
Utomilumab in Patients With Immune Checkpoint Inhibitor-Refractory Melanoma and Non-Small-Cell Lung Cancer.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- CD137L promotes immune surveillance in melanoma via HLTF regulation.Nature communications · 2025Article
- The next generation of immunotherapies for lung cancers.Nature reviews. Clinical oncology · 2025Review
- 4-1BB Antibodies in Oncology Clinical Trials: A Review.Journal of immunotherapy and precision oncology · 2025Review
- Primary and Acquired Resistance to Immunotherapy with Checkpoint Inhibitors in NSCLC: From Bedside to Bench and Back.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- First-in-human, multicenter, open-label, phase I study of ATOR-1017 (evunzekibart), a 4-1BB antibody, in patients with advanced solid malignancies.Journal for immunotherapy of cancer · 2025Article
- Targeting the TNF and TNFR superfamilies in autoimmune disease and cancer.Nature reviews. Drug discovery · 2024Review
- High 4-1BB Expression in PBMCs and Tumor Infiltrating Lymphocytes (TILs) in Patients with Head and Neck Squamous Cell Carcinoma.European journal of dentistry · 2024Article
- Commentary: On the Emerging Role of Innate Lymphoid Cells in Bladder Cancer.Journal of cancer immunology · 2024Article
- ATOR-1017 (evunzekibart), an Fc-gamma receptor conditional 4-1BB agonist designed for optimal safety and efficacy, activates exhausted T cells in combination with anti-PD-1.Cancer immunology, immunotherapy : CII · 2023Article
- XFab-α4-1BB/CD40L fusion protein activates dendritic cells, improves expansion of antigen-specific T cells, and exhibits antitumour efficacy in multiple solid tumour models.Cancer immunology, immunotherapy : CII · 2023Article
- Review
- NK Cell-Targeted Immunotherapies in Bladder Cancer: Beyond Checkpoint Inhibitors.Bladder cancer (Amsterdam, Netherlands) · 2023Review
- NK cell exhaustion in the tumor microenvironment.Frontiers in immunology · 2023Review
- Agonism of 4-1BB for immune therapy: a perspective on possibilities and complications.Frontiers in immunology · 2023Review
- Time to consider sequencing anti-inflammatory treatments with chemotherapy and immuno-stimulation?Frontiers in immunology · 2022Article
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Authors and funding
15 authors at 11 institutions in 3 countries.
Funding
Abstract
Section Head: Clinical/translational cancer immunotherapy. Background: The goal of this study was to estimate the objective response rate for utomilumab in adults with immune checkpoint inhibitor (ICI)-refractory melanoma and non-small-cell lung cancer (NSCLC). Methods: Utomilumab was dosed intravenously every 4 weeks (Q4W) and adverse events (AEs) monitored. Tumor responses by RECIST1.1 were assessed by baseline and on-treatment scans. Tumor biopsies were collected for detection of programmed cell death ligand 1, CD8, 4-1BB, perforin, and granzyme B, and gene expression analyzed by next-generation sequencing. CD8+ T cells from healthy donors were stimulated with anti-CD3 ± utomilumab and compared with control. Results: Patients with melanoma (n=43) and NSCLC (n=20) received utomilumab 0.24 mg/kg (n=36), 1.2 mg/kg (n=26), or 10 mg/kg (n=1). Treatment-emergent AEs (TEAEs) occurred in 55 (87.3%) patients and serious TEAEs in 18 (28.6%). Five (7.9%) patients discontinued owing to TEAEs. Thirty-two (50.8%) patients experienced treatment-related AEs, mostly grade 1-2. Objective response rate: 2.3% in patients with melanoma; no confirmed responses for patients with NSCLC. Ten patients each with melanoma (23.3%) or NSCLC (50%) had stable disease; respective median (95% confidence interval, CI) progression-free survival was 1.8 (1.7-1.9) and 3.6 (1.6-6.5) months. Utomilumab exposure increased with dose. The incidences of antidrug and neutralizing antibodies were 46.3% and 19.4%, respectively. Efficacy was associated with immune-active tumor microenvironments, and pharmacodynamic activity appeared to be blunted at higher doses. Conclusions: Utomilumab was well tolerated, but antitumor activity was low in patients who previously progressed on ICIs. The potential of 4-1BB agonists requires additional study to optimize efficacy while maintaining the tolerable safety profile.
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