Phase I study of [131I] ICF01012, a targeted radionuclide therapy, in metastatic melanoma: MELRIV-1 protocol

Emilie Thivat, Jacques Rouanet, Philippe Auzeloux, Nicolas Sas, Elodie Jouberton, Sophie Levesque, Tommy Billoux, Sandrine Mansard, Ioana Molnar, Marion Chanchou, Giovanna Fois, Lydia Maigne, Jean-Michel Chezal, Elisabeth Miot-Noirault, Michel D'Incan, Xavier Durando, Florent Cachin, Emilie Thivat, Jacques Rouanet, Philippe Auzeloux, Nicolas Sas, Elodie Jouberton, Sophie Levesque, Tommy Billoux, Sandrine Mansard, Ioana Molnar, Marion Chanchou, Giovanna Fois, Lydia Maigne, Jean-Michel Chezal, Elisabeth Miot-Noirault, Michel D'Incan, Xavier Durando, Florent Cachin

Abstract

Background: Benzamide-based radioligands targeting melanin were first developed for imaging melanoma and then for therapeutic purpose with targeted radionuclide therapy (TRT). [131I]ICF01012 presents a highly favorable pharmacokinetics profile in vivo for therapy. Tumour growth reduction and increase survival have been established in preclinical models of melanoma. According the these preclinical results, we initiate a first-in-human study aimed to determine the recommended dose of [131I]ICF01012 to administer for the treatment of patients with pigmented metastatic melanoma.

Methods: The MELRIV-1 trial is an open-label, multicentric, dose-escalation phase I trial. The study is divided in 2 steps, a selection part with an IV injection of low activity of [131I]ICF01012 (185 MBq at D0) to select patients who might benefit from [131I]ICF01012 TRT in therapeutic part, i.e. patient presenting at least one tumour lesion with [131I]ICF01012 uptake and an acceptable personalized dosimetry to critical organs (liver, kidney, lung and retina). According to dose escalation scheme driven by a Continual Reassessment Method (CRM) design, a single therapeutic injection of 800 MBq/m2, or 1600 MBq/m2, or 2700 MBq/m2 or 4000 MBq/m2 of [131I]ICF01012 will be administered at D11 (± 4 days). The primary endpoint is the recommended therapeutic dose of [131I]ICF01012, with DLT defined as any grade 3-4 NCI-CT toxicity during the 6 weeks following therapeutic dose. Safety, pharmacokinetic, biodistribution (using planar whole body and SPECT-CT acquisitions), sensitivity / specificity of [131I]ICF01012, and therapeutic efficacy will be assessed as secondary objectives. Patients who received therapeutic injection will be followed until 3 months after TRT. Since 6 to 18 patients are needed for the therapeutic part, up to 36 patients will be enrolled in the selection part.

Discussion: This study is a first-in-human trial evaluating the [131I]ICF01012 TRT in metastatic malignant melanomas with a diagnostic dose of the [131I]ICF01012 to select the patients who may benefit from a therapeutic dose of [131I]ICF01012, with at least one tumor lesion with [131I]ICF01012 uptake and an acceptable AD to healthy organ.

Trial registration: Clinicaltrials.gov : NCT03784625 . Registered on December 24, 2018. Identifier in French National Agency for the Safety of Medicines and Health Products (ANSM): N°EudraCT 2016-002444-17.

Keywords: Dosimetry; Metastatic melanoma; Targeted radionuclide therapy; [131I]ICF01012.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

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