Safety and activity of the first-in-class locked nucleic acid (LNA) miR-221 selective inhibitor in refractory advanced cancer patients: a first-in-human, phase 1, open-label, dose-escalation study.

"Declarations Ethics approval and consent to participateThe clinical study protocol has been approved by the Regulatory Authorities AIFA/ISS (Italy) (AIFA/SC/P/34930-27/05/2018, amendment AIFA/SC/P/4261—15/01/2020) and by the local Ethics Committee (n. 207-19/07/2018, amendment n.18 -16/01/2020). All patients wrote an informed consent to participate in the study. Competing interestsP.T., M.T.D.M., and P.T. are inventors of patents (US 9,404,111 B2; EPO 2943570; C.C.I.A.A. 0001429326) that are owned by Magna Graecia University, Catanzaro, Italy. All other authors declare no competing interests. Competing interests P.T., M.T.D.M., and P.T. are inventors of patents (US 9,404,111 B2; EPO 2943570; C.C.I.A.A. 0001429326) that are owned by Magna Graecia University, Catanzaro, Italy. All other authors declare no competing interests."

"Funding This study reported in this manuscript was supported by the Charity Italian Association for Cancer Research (AIRC) Special Program Molecular Clinical Oncology—“5 × 1000” no. 9980 (2010-15) and its Extension Program no. 9980 (2016-17), (PI: Pierfrancesco Tassone). AIRC had no role in study design, data collection, analysis, interpretation, manuscript writing or the decision to publish the results of the study."

"We enrolled patients with advanced solid tumors in a first-in-human, phase I, open-label, dose-escalation study. Patients were recruited at one site, the Magna Graecia University/AOU Mater Domini Hospital (now AOU Renato Dulbecco), Catanzaro, Italy. The study was approved by the Regulatory Authorities AIFA/ISS (Italy) in March 2018 and the local Ethics Committee in July 2018. The first patient was enrolled on February 2019, and the study was closed on December 2021. The study was registered during the trial conduction, after accrual of 10 patients (ClinTrials.Gov NCT04811898). The design of the trial is shown in the Additional file : Fig. S1. Additional information on study protocol is available online (access provided in the Additional file : Supplementary material). The study was conducted in accordance with the principles of the Declaration of Helsinki, Good Clinical Practice guidelines of the International Council for Harmonisation, and applicable laws. The study was fully academic, and funds were made available by “A Special Program Molecular Clinical Oncology—“5 × 1000” no. 9980 (2010-15) and its Extension Program no. 9980 (2016-17). Data were collected by the investigators, CRF stored according to GCP criteria, analysed by statisticians paid by the Institution, and interpreted by all the authors."