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A phase I study of the safety and tolerability of VLX600, an Iron Chelator, in patients with refractory advanced solid tumors
Mayo Clin, Div Hematol & Med Oncol, Jacksonville, FL 32224 USA;Mayo Clin Florida, Div Hematol Oncol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA.
Mayo Clin, Div Med Oncol, Rochester, MN USA.
Mayo Clin, Div Hematol & Med Oncol, Jacksonville, FL 32224 USA.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
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2019 (English)In: Investigational new drugs, ISSN 0167-6997, E-ISSN 1573-0646, Vol. 37, no 4, p. 684-692Article in journal (Refereed) Published
Abstract [en]

Introduction VLX600 is a novel iron chelator designed to interfere with intracellular iron metabolism, leading to inhibition of mitochondrial respiration and bioenergetic catastrophe and resultant tumor cell death. Methods We conducted a multicenter, phase 1, dose escalation study to determine the safety and adverse event profile and the maximum tolerated dose and recommended phase 2 dose of VLX600. Other endpoints included pharmacokinetics, and preliminary evidence of anti-cancer efficacy as assessed according to RECIST 1.1 criteria. VLX600 was administered intravenously on days 1, 8, and 15 of each 28-day treatment cycle. Results Nineteen patients were enrolled, and seventeen received at least one dose of VLX600. Dose increments were reduced to 50% after dose level 3 (40mg) due to the occurrence of a grade 3 pulmonary embolism. The study was then closed early due to slow recruitment. No maximum tolerated dose (MTD) nor RP2D had been identified at the time of study closure. Overall, the drug was well tolerated and no DLTs were observed. Fourteen patients experienced drug-related adverse events of any grade. The most frequently reported drug-related AEs were fatigue, nausea, constipation, vomiting, increased alkaline phosphatase, anemia, and decreased appetite. No formal efficacy or survival analyses were performed. No objective responses were observed, though six patients (32%) had stable disease as best response. Conclusion VLX600 was reasonably well tolerated and, together with preclinical data, there is support for further efforts to explore its activity as single agent and in combination with drugs or radiation.

Place, publisher, year, edition, pages
SPRINGER , 2019. Vol. 37, no 4, p. 684-692
Keywords [en]
Clinical trial, Phase 1, Iron chelating agents, VLX600
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-390390DOI: 10.1007/s10637-018-0703-9ISI: 000475627500010PubMedID: 30460505OAI: oai:DiVA.org:uu-390390DiVA, id: diva2:1341557
Available from: 2019-08-09 Created: 2019-08-09 Last updated: 2019-08-09Bibliographically approved

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Nygren, PeterGullbo, Joachim

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