(P 564) A PILOT STUDY OF LYSO-THERMOSENSITIVE LIPOSOMAL DOXORUBICIN AND MAGNETIC RESONANCE-GUIDED HIGH INTENSITY FOCUSED ULTRASOUND FOR TREATMENT OF RELAPSED OR REFRACTORY SOLID TUMORS

Objective: Current therapies for many pediatric solid tumors have reached maximal dose intensification and the acute and late effects of therapy are substantial. Magnetic Resonance-guided High Intensity Focused Ultrasound (MR-HIFU) is an innovative technology that enables precise thermal ablation by focusing ultrasound energy inside a tumor using an external applicator that is completely non-invasive and uses no ionizing radiation. In addition, pre-clinically, this therapy has been shown to amplify anti-tumor effects by causing a local inflammatory response, increasing antigen presentation and T-cell activation against tumor antigens. Lyso-thermosensitive liposomal doxorubicin (LTLD, ThermoDox®) is a special formulation that enables heat-activated release of doxorubicin. MR-HIFU provides precise and flexible control over local heating with hyperthermia (40-45ºC) and ablative temperatures (>55ºC). MR-HIFU is thus an ideal system to use with LTLD, as it can both trigger drug release with mild hyperthermia and prevent drug washout using ablation and associated vascular shutdown.
The primary objectives of this study are to determine the response rate of targeted tumors to LTLD administered in combination with MR-HIFU hyperthermia followed by an ablation therapy in subjects with relapsed/refractory solid tumors, and to evaluate toxicity and safety of this combination therapy in subjects with refractory cancer. Exploratory objectives include evaluation of changes in pharmacodynamic immune biomarkers, radiographic response in non-target (not treated with HIFU) areas, and patient reported outcomes of pain and impact of pain on daily activities.

Methods: This is an open label pilot study evaluating LTLD with MR-HIFU hyperthermia followed by ablation (NCT04791228). Patients ≥12 years old with histologically confirmed relapsed/refractory measurable/evaluable solid tumors are eligible. Patients must have target lesions located in sites accessible to MR-HIFU. Adequate organ function, including cardiac function, is required. Prior anthracycline dosing must be ≤450 mg/m2.
On day 1 of a 21-day cycle, LTLD will be administered intravenously over 30 minutes at the adult recommended phase 2 dose of 50 mg/m2. The infusion will be followed immediately (+/- 30 minutes) by one hour of MR-HIFU mild hyperthermia (40-45°C) and subsequent ablation (> 55°C) of the target volume.
Therapy may continue for up to 6 total cycles if treatment is tolerated, patients have at least stable disease in treated lesions, and lifetime cumulative anthracycline dose of 600 mg/m2 is not exceeded. Outcome will be measured by imaging using modified RECISTv1.1 criteria. Patient reported outcome measurements of pain and quality of life as well as pharmacodynamic and immune markers in peripheral blood will be evaluated pre and post therapy to evaluate for any exploratory changes.

Results: N/A, trials in progress

Conclusion: N/A, trials in progress