ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Phase IB Study of GITR Agonist Antibody TRX518 Singly and in Combination with Gemcitabine, Pembrolizumab, or Nivolumab in Patients with Advanced Solid Tumors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 47 citations in OpenAlex.
- Phase 1/2 study of INCAGN01876, an anti-glucocorticoid-induced tumor necrosis factor receptor agonist monoclonal antibody, plus immunotherapy for advanced cancers.The oncologist · 2026Trial
- First-in-Human Phase I/II Study of INCAGN01876, a Glucocorticoid-Induced Tumor Necrosis Factor Receptor Agonist, in Patients with Advanced or Metastatic Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- CD8⁺ T Cell infiltration and spatial organization in cancer: mechanisms, barriers, and therapeutic strategies.Molecular biomedicine · 2026Review
- Fc-optimized GITR antibody enhances a CD4 T cell-dendritic cell crosstalk to promote antitumor immunity.Nature cancer · 2026Article
- GITR activation potentiates anti-tumor immunity of tumor-infiltrating lymphocytes expanded from glioblastoma by rescuing exhaustion.Oncogene · 2026Article
- T-Cell Immunity and Lung Cancer.Respirology (Carlton, Vic.) · 2026Review
- Tumor microenvironment-induced epigenetic reprogramming of Tregs and its impact on immunotherapy.Frontiers in genetics · 2026Review
- Review
- Regulatory T cells in cancer anti-PD-(L)1 therapy.Human cell · 2025Review
- Post-translational modifications of cancer immune checkpoints: mechanisms and therapeutic strategies.Molecular cancer · 2025Review
- Emerging Immunotherapy Targets in Early Drug Development.International journal of molecular sciences · 2025Review
- Targeting novel regulated cell death: disulfidptosis in cancer immunotherapy with immune checkpoint inhibitors.Biomarker research · 2025Review
- Single-Cell RNA Profiling of Ocular Adnexal Sebaceous Carcinoma Reveals a Complex Tumor Microenvironment and Identifies New Biomarkers.American journal of ophthalmology · 2025Observational
- Enhanced anti-tumor efficacy of tumor-infiltrating lymphocytes by GITR agonist in ovarian cancer.Frontiers in immunology · 2025Article
- Emerging IO checkpoints in gastrointestinal oncology.Frontiers in immunology · 2025Review
- A landscape of checkpoint blockade resistance in cancer: underlying mechanisms and current strategies to overcome resistance.Cancer biology & therapy · 2024Review
- Targeting the TNF and TNFR superfamilies in autoimmune disease and cancer.Nature reviews. Drug discovery · 2024Review
- Quantitative Approach to Explore Regulatory T Cell Activity in Immuno-Oncology.Pharmaceutics · 2024Review
- Regulatory T cells in immune checkpoint blockade antitumor therapy.Molecular cancer · 2024Review
- Multi-stage mechanisms of tumor metastasis and therapeutic strategies.Signal transduction and targeted therapy · 2024Review
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Authors and funding
18 authors at 8 institutions in 2 countries.
Funding
Abstract
purposeTRX518 is a mAb engaging the glucocorticoid-induced TNF receptor-related protein (GITR). This open-label, phase I study (TRX518-003) evaluated the safety and efficacy of repeated dose TRX518 monotherapy and in combination with gemcitabine, pembrolizumab, or nivolumab in advanced solid tumors. PATIENTS AND
methodsTRX518 monotherapy was dose escalated (Part A) and expanded (Part B) up to 4 mg/kg loading, 1 mg/kg every 3 weeks. Parts C-E included dose-escalation (2 and 4 mg/kg loading followed by 1 mg/kg) and dose-expansion (4 mg/kg loading) phases with gemcitabine (Part C), pembrolizumab (Part D), or nivolumab (Part E). Primary endpoints included incidence of dose-limiting toxicities (DLT), serious adverse events (SAE), and pharmacokinetics. Secondary endpoints were efficacy and pharmacodynamics.
resultsA total of 109 patients received TRX518: 43 (Parts A+B), 30 (Part C), 26 (Part D), and 10 (Part E), respectively. A total of 67% of patients in Parts D+E had received prior anti-PD(L)1 or anti-CTLA-4. No DLTs, treatment-related SAEs, and/or grade 4 or 5 AEs were observed with TRX518 monotherapy. In Parts C-E, no DLTs were observed, although TRX518-related SAEs were reported in 3.3% (Part C) and 10.0% (Part E), respectively. Objective response rate was 3.2%, 3.8%, 4%, and 12.5% in Parts A+B, C, D, and E, respectively. TRX518 affected peripheral and intratumoral regulatory T cells (Treg) with different kinetics depending on the combination regimen. Responses with TRX518 monotherapy+anti-PD1 combination were associated with intratumoral Treg reductions and CD8 increases and activation after treatment.
conclusionsTRX518 showed an acceptable safety profile with pharmacodynamic activity. Repeated dose TRX518 monotherapy and in combination resulted in limited clinical responses associated with immune activation. See related commentary by Hernandez-Guerrero and Moreno, p. 3905.
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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 OpenQuestion graph.