ArticleESMO open2016
Safety and activity of IT-139, a ruthenium-based compound, in patients with advanced solid tumours: a first-in-human, open-label, dose-escalation phase I study with expansion cohort.
Article in ESMO open, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01415297 (A Phase I Dose Escalation Study of NKP-1339 Administered on Days 1, 8 and 15 of Each 28-Day Cycle in Patients With Advanced Solid Tumors Refractory to Treatment), which is not on this map. Cited by 78 papers, 1 of them a synthesis that pooled it.
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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 Phase I Dose Escalation Study of NKP-1339 Administered on Days 1, 8 and 15 of Each 28-Day Cycle in Patients With Advanced Solid Tumors Refractory to Treatment
Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 151 citations in OpenAlex.
- Unveiling the dark side of glucose-regulated protein 78 (GRP78) in cancers and other human pathology: a systematic review.Molecular medicine (Cambridge, Mass.) · 2023Pooled it
- BOLD-100 treatment induces systemic lipid crosstalk in metastatic colorectal carcinoma patients in a combination treatment with FOLFOX.iScience · 2026Article
- Effect of the µ-Diphosphine Bridging Ligand on the Cytotoxic Activity of Homodinuclear Ruthenium Complexes.Molecules (Basel, Switzerland) · 2026Article
- New Ru(III) NAMI/NAMI-A Analogue Complexes with Selective Anticancer Activity.Journal of medicinal chemistry · 2026Article
- Mitochondria-Targeting Metal Complexes: Design Principles, Mechanisms of Action, and Translational Perspectives.Biomolecules · 2026Review
- Combinational studies of BOLD-100/KP1339 with established chemotherapeutics in gastrointestinal multicellular tumor spheroids.Cancer chemotherapy and pharmacology · 2026Article
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- Bidirectional crosstalk between ER stress and lipid metabolism: From proteostasis to tumor adaptation.Cell death discovery · 2025Review
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- The Role of Metallodrugs in Enhancing Neuroendocrine Neoplasm Therapies: The Promising Anticancer Potential of Ruthenium-Based Complexes.Molecules (Basel, Switzerland) · 2025Review
- Endoplasmic reticulum stress responses in anticancer immunity.Nature reviews. Cancer · 2025Review
- Raphin-1 mediates the survival and sensitivity to radiation of pediatric-type diffuse high-grade glioma via phosphorylated eukaryotic initiation factor 2α-dependent and -independent processes.Molecular oncology · 2025Article
- Machine Learning-Enhanced Calculation of Quantum-Classical Binding Free Energies.Journal of chemical theory and computation · 2025Article
- Unraveling BOLD-100 synergistic potential in pleural mesothelioma treatment: an in vitro study.Investigational new drugs · 2025Article
- The Combination of Active-Targeted Photodynamic Therapy and Photoactivated Chemotherapy for Enhanced Cancer Treatment.Journal of biophotonics · 2025Review
- Article
- GRP78 as a potential therapeutic target in cancer treatment: an updated review of its role in chemoradiotherapy resistance of cancer cells.Medical oncology (Northwood, London, England) · 2025Review
- Synthesis and Evaluation of Cytotoxic Activity of RuCp(II) Complexes Bearing (Iso)nicotinic Acid Based Ligands.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Platinum-group metal half-sandwich complexes of 1-(α-d-glucopyranosyl)-4-hetaryl-1,2,3-triazoles: synthesis, solution equilibrium studies, and investigation of their anticancer and antimicrobial activities.Frontiers in chemistry · 2025Article
- Ultrasound-Targeted Nanobubbles Codelivering NKP-1339 and miR-142-5p for Synergistic Mitochondrial Immunogenic Cell Death and PD-L1 Inhibition in Cancer Therapy.Biomaterials research · 2025Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThis phase I clinical study (NCT01415297) evaluated the safety, tolerability, maximum-tolerated dose (MTD), pharmacokinetics and pharmacodynamics of IT-139 (formerly NKP-1339) monotherapy in patients with advanced solid tumours. IT-139, sodium trans-(tetrachlorobis(1H-indazole)ruthenate(III)), is a novel small molecule that suppresses the stress induction of GRP78 in tumour cells. GRP78 is a key regulator of misfolded protein processing, and its upregulation in tumours is associated with intrinsic and drug-induced resistance.
methodsForty-six patients with advanced solid tumours refractory to treatment received intravenous infusions of IT-139 on days 1, 8 and 15 for every 28 days, and doses were evaluated across nine cohorts at 20, 40, 80, 160, 320, 420, 500, 625 and 780 mg/m
resultsOverall, IT-139 was well tolerated. The treatment-emergent adverse events (AEs) occurring in ≥20% of patients were nausea, fatigue, vomiting, anaemia and dehydration. The majority of patients had AEs that were ≤grade 2, regardless of relationship with the study drug. Of the total 38 efficacy-evaluable patients, one patient with a carcinoid tumour achieved a durable partial response. Nine additional patients achieved stable disease . The MTD was determined to be 625 mg/m
conclusionsIT-139 demonstrated a manageable safety profile at the MTD and modest anti-tumour activity in this study of patients with solid tumours refractory to treatment. The lack of dose-limiting haematological toxicity and the absence of neurotoxicity position IT-139 well for use in combination with a broad spectrum of anticancer drugs. TRIAL REGISTRATION NUMBER: NCT01415297.
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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.