intratumoral targeted hyperthermia therapy (tht) for cutaneous metastatic melanoma

Conditions: Cutaneous Metastatic Melanoma

Summary: this device phase i/ii, first in human, early feasibility study (efs), open-label, single-arm trial aims to evaluate the safety, tolerability, and preliminary efficacy of gold nanorod (gnr)-enabled sub-ablative targeted hyperthermia therapy (tht) in patients with unresectable stage 3c/3d/4m1 cutaneous metastatic malignant melanoma that have failed to respond to systemic checkpoint and localized intra-tumoral immunotherapy. the study will involve up to 10 participants with stable or progressive cutaneous and/or subcutaneous skin lesions (immune stable disease (isd) or immune confirmed/unconfirmed progressive disease (icpd/iupd)). gnrs, when administered via intra-tumoral injection and activated by nir light, generate localized heat through a process called tht. this approach selectively targets tumor cells while minimizing damage to surrounding healthy tissue. in this study, 10 participants will receive two tht treatments spaced 7 days apart. the primary objective of this study is to assess the safety and tolerability of tht treatment.


Eligibility criteria:
inclusion criteria: 1. 16 years of age or older; 2. participants with histologically or cytologically confirmed stage 3c/3d/4m1 advanced or cutaneous metastatic melanoma, with measurable disease by irecist 1.1 criteria, including any number of cutaneous lesions; 3. present a visible and accessible primary tumor or metastatic deposit (any site) that has not been surgically removed; 4. present target tumors of ≤2.5 cm in diameter; 5. participants must have received and failed systemic and local intra-tumoral therapy at least one prior standard therapy, including immune checkpoint inhibitors (e.g., anti- pd1 or anti-ctla-4), and failed local intra-tumoral il-2 treatment. failed response to treatment will be categorized according to irecist guidelines. patients who have: a) immune partial response (ipr): at least a 30% decrease in the sum of diameters of target lesions compared to baseline, no progression of non-target lesions, no new lesions; or b) immune stable disease (isd): neither sufficient reduction to qualify for ipr nor sufficient increase to qualify for icpd (immune confirmed progressive disease), no new lesions; or c) immune unconfirmed progressive disease (iupd): at least a 20% increase in the sum of diameters of target lesions, taking the smallest sum on study as the reference, appearance of new lesions, iupd needs confirmation after at least 4 weeks; if confirmed, it becomes icpd; or d) immune confirmed progressive disease (icpd): iupd must be confirmed in a follow-up assessment (minimum of 4 weeks after initial iupd), if progressive disease (increase in lesion size or additional new lesions) is still evident upon re-evaluation, icpd is confirmed. 6. participants must agree to discontinue treatment with local intralesional immunotherapies during the study, with resumption after completion of the trial; 7. ecog performance status: ≤1; 8. life expectancy: ≥6 months; 9. participants able and willing to provide written informed consent and comply with the trial protocol. 10. either braf positive (braf+) or braf negative (braf-). exclusion criteria: 1. women who are pregnant, breastfeeding, or planning to become pregnant during the study. women of childbearing potential must have a negative pregnancy test within 72 hours prior to enrollment and agree to use adequate contraception throughout the study; 2. any infection requiring systemic therapy or other concurrent medical conditions (e.g., hepatitis b, hepatitis c, hiv) that would interfere with the study; 3. myocardial infarction or stroke within the past 6 months, uncontrolled angina, or significant arrhythmia; 4. participants receiving blood thinners as part of therapeutic anticoagulation therapy; 5. any severe or uncontrolled comorbid condition that, in the investigator's opinion, would pose excessive risk to the participants (e.g., immunodeficiencies, severe hypertension, uncontrolled diabetes, liver failure); 6. participation in another clinical trial involving an investigational product/device within 30 days prior to screening; 7. any condition that would impede compliance with study procedures; 8. participants with a known allergy to gold of any kind; 9. participants who are unable to tolerate cutaneous injections for any reason will not be eligible; 10. participants with a known allergy to injectable local analgesics; 11. participants with ocular melanoma or melanoma involving periorbital skin.

Keywords: hyperthermia gold nanorods targeted hyperthermia near infrared light cutaneous metastatic melanoma treatment immunotherapy