Overview

This is an open-label, multicenter Phase I/II clinical study conducted in participants with unresectable locally advanced or metastatic melanoma, aiming to evaluate the safety, tolerability, pharmacokinetic characteristics, and efficacy of JMT108 Injection in this population. The study consists of Phase I and Phase II (including Phase IIa and Phase IIb), where Phase I is the dose-escalation stage, Phase IIa is the dose-expansion stage, and Phase IIb is the cohort-expansion stage.

Eligibility

Inclusion Criteria:

1. Age≥18 years old.
2. Histologically or cytologically confirmed unresectable locally advanced or metastatic melanoma.
3. Participants with unresectable locally advanced or metastatic melanoma who have failed prior standard treatment or have no available standard treatment will be enrolled in Phase I and Phase IIa; those who have received or not received prior standard treatment will be enrolled in Phase IIb.
4. According to the response evaluation criteria for solid tumors (RECIST 1.1), having at least one measurable lesion.
5. ECOG PS of 0-1.
6. Expected survival ≥ 3 months.
7. Participants with adequate organ functions.
8. Female and male patients of childbearing age agree to take adequate contraceptive measures during and upon completion of the study for 6 months after the last dose. Female participants of childbearing age must have a negative blood pregnancy test within 7 days before the first dose or randomization.
9. Voluntarily agree to participate in the study and sign the informed consent.

Exclusion Criteria:

1. Received chemotherapy, radiotherapy, biotherapy, endocrine therapy, targeted therapy, immunotherapy, or other unapproved clinical trial drugs or treatments within 4 weeks prior to the first administration of the study drug.
2. Prior use of IL-2/IL-15 cytokine therapy.
3. Received major organ surgery (excluding needle biopsy) or experienced severe trauma within 4 weeks prior to the first administration of the study drug, or requires elective surgery during the study period.
4. Received systemic glucocorticoids or other immunosuppressive therapy within 14 days prior to the first use of the study drug. Exceptions include the following situations: receiving physiological replacement doses of hydrocortisone or other equivalent doses of hormonal therapy (i.e., prednisone ≤ 10 mg/day or other equivalent doses of hormones); receiving topical, ophthalmic, intra-articular, intranasal, and inhaled glucocorticoid therapy; receiving short-course glucocorticoids for preventive treatment (e.g., prevention of contrast agent allergy).
5. Known active central nervous system (CNS) metastases and/or leptomeningeal metastases. Patients with stable brain metastases who do not require local treatment for brain metastases are eligible for inclusion.
6. Patients with active infections requiring intravenous anti-infective therapy within 14 days prior to the first administration.
7. Has a history of severe cardiovascular and cerebrovascular diseases.
8. Has active or recurrent autoimmune diseases.
9. Has a known history of receiving immunotherapy with the occurrence of grade ≥3 immune-related adverse events (irAEs) (excluding immune-related endocrine abnormalities that have been stabilized) or grade ≥2 immune-related myocarditis.
10. Has a history of arterial or venous thrombosis within 6 months prior to the first administration.
11. Has a history of serous effusions such as ascites or pleural effusion requiring drainage within 14 days prior to the first administration.
12. Has a history of other malignant tumors within 5 years prior to the first administration or concurrent other malignant tumors.