A phase I study of the safety and tolerability of VLX600, an Iron Chelator, in patients with refractory advanced solid tumors
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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 (40 mg) 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.
KeywordsClinical trial Phase 1 Iron chelating agents VLX600
The study reported herein was supported by Vivolux AB.
Compliance with ethical standards
Conflict of interest
Research Support) Senwha Biociences Inc., Tracon Pharmaceuticals, Genentech; Astrazeneca/Medimmune; Arqule, Inc.; Agios; Taiho Oncology; Boston Biomedical; Ipsen.
Consulting/Advisory Board) Eisai Co, Ltd., Bayer Pharmaceuticals.
Research Support) Boston Biomedical, miRNA Therapeutics, Senwha Biociences Inc., Astrazeneca/Medimmune, BiolineRx, Agios, Halozyme, Celgene, Threshold Pharmaceuticals, Toray Industries, Dicerna, Sillajen, Eisai, Taiho Pharmaceuticals, EMD Serono, Isis Pharmaceuticals, Incyte, Sun Biopharma, Ariad, ImClone Systems, QED Therapeutics.
Consulting/Advisory Board) G1 Therapeutics, TD2, Fujifilm, Agios, Insys Therapeutics, Novartis, ArQule, Celgene, Inspyr Therapeutics, Halozyme, Pieris Pharmaceuticals, Taiho Pharmaceuticals.
Stock and Other Ownership Interests) GlaxoSmithKline, Gilead Sciences, AVEO.
Travel, Accomodations, Expenses) ArQule, Celgene, Astrazeneca.
Research Support) NIH, Novartis and Verily.
Consulting/Advisory Board) Honoraria are paid to institution for participation in advisory boards for Abbvie, BMS and Genentech.
Peter Nygren: shareholder in Vivolux AB.
Joachim Gulbo: shareholder in and consultant to Vivolux AB.
All other authors have no relevant conflicts of interest to disclose.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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