Abstract CT246: An open-label, single-center, phase 0, microdose study to demonstrate delivery of TTX-MC138-NODAGA-Cu64 to radiographically confirmed metastases in subjects with advanced solid tumors
Authors: Varkaris Andreas , Caravan Peter , Robertson Neil , Ghosh Subrata , Warren Michael , Medarova Zdravka , Duggan Susan 
Published: April 2023

Abstract
Purpose: Cu-64 labeled TTX-MC138, a microRNA-10b (miR-10b) inhibitor, will be evaluated in a Phase 0 clinical study conducted under an Exploratory IND to evaluate delivery of the molecule to metastatic lesions in subjects with advanced solid tumors by using positron emission tomography-magnetic resonance imaging (PET-MRI).
Background: miR10b is a master regulator of the viability of metastatic tumor cells and promotes capacity of tumor cells to migrate and invade surrounding tissue. These findings prompted design of a miR10b-targeted therapeutic consisting of an anti-miR10b antagomir conjugated to ultrasmall iron oxide nanoparticles (MN), termed TTX-MC138. In mouse models of cancer, TTX-MC138 caused durable regressions of established metastases with no systemic toxicity. Clinical development will investigate if TTX-MC138 would accumulate in clinical metastases. TTX-MC138 is radiolabeled with isotope Cu-64 to generate the radiopharmaceutical TTX-MC138-NODAGA-Cu64. PET-MRI will assess pharmacokinetics (PK) of the radiolabeled product in humans and determine uptake in metastatic lesions.
Methods: This open-label, single-center, single-arm, phase 0, microdose study in subjects with advanced solid tumors and radiographically confirmed metastases will evaluate delivery of TTX-MC138-NODAGA-Cu64 by using PET-MRI; establish PK of TTX-MC138-NODAGA-Cu64; and assess safety of TTX-MC138-NODAGA-Cu64. Approximately 12 subjects age ≥ 18 years are expected to be enrolled in the study. Eligible subjects will have confirmed diagnosis of at least 1 metastatic solid tumor (that is not amenable to curative therapy unless participation in the study would delay standard therapy), Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, and at least 1 target lesion per Response Evaluation Criteria in Solid Tumors version 1.1 (at least 10 mm per MRI from fludeoxyglucose [FDG] PET-MRI). Study duration is up to 46 days and includes a screening visit, dosing period (2 visits), and a follow-up visit. On Day 1, subjects receive 1 microdose of TTX-MC138-NODAGA-Cu64 by intravenous bolus. Days 1 and 2 include whole body PET-MRI imaging, ECG and blood collection. Safety data are collected at all visits. A Data Review Committee may review specific study data, including safety data. The primary endpoint will measure percent injected dose per cubic centimeter (%ID/cc) tissue of TTX-MC138-NODAGA-Cu64 delivered to metastatic lesions. Secondary endpoints may include evaluation of PK of key components of TTX-MC138-NODAGA-Cu64, metabolite analysis, and target engagement. Safety data, including incidence of adverse events, clinical lab data, ECGs, vital signs and concomitant medications, will be summarized. Enrollment is expected to start in 2023.
Citation Format: Andreas Varkaris, Peter Caravan, Neil Robertson, Subrata Ghosh, Michael Warren, Zdravka Medarova, Susan Duggan. An open-label, single-center, phase 0, microdose study to demonstrate delivery of TTX-MC138-NODAGA-Cu64 to radiographically confirmed metastases in subjects with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT246.