Advanced melanoma
Conditions
Interventions
Dose-Escalation Cohorts:Intratumoral Au-TMP injection (initial dose 5% tumor volume, escalated to 10% and 20% tumor volume) combined with radiotherapy (6Gy/f * 5f) followed by anti-PD-1 therapy (torip
Sponsors
West China Hospital, Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Age >=18 years, with no upper age limit; 2. ECOG performance status of 0 or 1; 3. No prior systemic therapy for histologically confirmed unresectable Stage III or IV melanoma. Prior adjuvant or neoadjuvant therapy is permitted, provided it was completed at least 3 weeks before randomization and all related adverse events have resolved to normal or Grade I as per CTCAE criteria; 4. Presence of measurable lesions (per RECIST v1.1): At least one lesion that can be accurately measured by imaging or clinical examination. Imaging-measurable lesions are defined as: non-nodal lesions with a longest diameter >=10 mm on CT/MRI with 5 mm slice thickness, nodal lesions with a short axis >=15 mm, or non-nodal lesions with a longest diameter >=20 mm on chest X-ray with good contrast. Clinically measurable lesions are defined as: superficial lesions (e.g., skin nodules) with a longest diameter >=10 mm measured by calipers. 5. At least one lesion suitable for intratumoral injection and radiotherapy (located in the skin, subcutaneous tissue, superficial lymph nodes, or visceral sites deemed safe upon evaluation), and no prior radiotherapy to this lesion (unless clear progression has occurred); 6. Adequate hematologic and end-organ function within 7 days before the first dose, meeting the following laboratory criteria: (1) Hematology: Absolute neutrophil count (ANC) >=1.5×10^9/L without use of granulocyte colony-stimulating factor (G-CSF) within 14 days prior to the test; Platelet count (PLT) >=90×10^9/L without platelet transfusion within 14 days prior to the test; Hemoglobin (Hb) >=90 g/L without red blood cell transfusion or erythropoietin use within 14 days prior to the test; (2) Renal function: Serum creatinine (Cr) =50 mL/min calculated by the Cockcroft-Gault formula (only if baseline Cr >1.5×ULN); (3) Hepatic function: Total bilirubin (TBIL) =2.8 g/dL; (4) Coagulation function: International Normalized Ratio (INR) or Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) =50%; 7. Life expectancy >=16 weeks; 8. Use of highly effective contraception during the study and for 12 months after treatment completion; 9. Voluntary participation in the study, signed informed consent, good compliance, and cooperation with follow-up.
Exclusion criteria
Exclusion criteria: 1. Prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy; 2. Known hypersensitivity to recombinant humanized anti-PD-1 monoclonal antibody drugs and their components; 3. Active skin breakdown, infection, ulceration, necrosis, or bleeding at the injection site, or risk of hollow organ perforation; 4. Known allergy or intolerance to the active ingredient Au-TMP, excipients, or similar compounds; 5. Presence of known driver gene mutations (e.g., BRAF V600E/K, c-KIT, NRAS, etc.) for which approved first-line targeted therapies are available; 6. Malignant melanoma originating from the eye or mucosa; 7. Receipt of other anti-tumor therapies (including corticosteroids or immunotherapy) or participation in other clinical trials within 4 weeks before treatment initiation, or failure to recover from previous toxicity (except Grade 2); 8. Pregnant or lactating women; 9. HIV positive; HCV positive; HBsAg or HBcAb positive with simultaneous detection of positive HBV DNA copies (quantitative detection >=500 IU/ml); 10. History of active tuberculosis; 11. Active autoimmune disease requiring systemic treatment within the past 2 years (e.g., use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Related replacement therapies are permitted (e.g., thyroxine, insulin, or physiological corticosteroid replacement therapy for renal or pituitary insufficiency); 12. Other serious, uncontrolled concomitant diseases that may affect protocol compliance or interfere with the interpretation of results, including active opportunistic infections or progressive (severe) infections, uncontrolled diabetes, cardiovascular diseases (NYHA Class III or IV heart failure, cardiac conduction block greater than Grade II, myocardial infarction within the past 6 months, unstable arrhythmia or unstable angina, cerebral infarction within the past 3 months, etc.), or pulmonary diseases (interstitial pneumonia, obstructive pulmonary disease, and history of symptomatic bronchospasm); 13. Exclusion of subjects with active central nervous system metastases, including active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if they have received treatment, and there is no evidence of disease progression on MRI at least 8 weeks after completion of treatment and within 28 days before the first dose. Additionally, systemic corticosteroid treatment at immunosuppressive doses (>10 mg/day prednisone equivalent) must not be required for at least 2 weeks before study drug administration; 14. Patients who received hematopoietic stimulating factors, such as colony-stimulating factors or erythropoietin, within 2 weeks before treatment initiation; 15. Receipt of live vaccines within 4 weeks before treatment initiation; 16. Major surgery (excluding diagnostic surgery) within 4 weeks before treatment initiation; 17. History of psychiatric drug abuse that cannot be discontinued, or history of psychiatric disorders; 18. Other unresolved malignancies diagnosed within the past 5 years, excluding clearly cured malignancies or curable cancers, such as basal cell carcinoma or squamous cell carcinoma of the skin, superficial bladder cancer, prostate carcinoma in situ, cervical carcinoma in situ, or breast carcinoma in situ; 19. In the investigator's opinion, other severe, acute, or chronic medical or psychiatric conditions or laboratory abnormalities that may increase the risks associated with study participation or may interfere with
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Dose-Limiting Toxicities (DLTs); | — |
Secondary
| Measure | Time frame |
|---|---|
| Incidence and Severity of Adverse Events;Pharmacokinetic (PK) Parameters;Objective Response Rate (ORR); | — |
Countries
China
Contacts
Public ContactPeng Xingchen
West China Hospital, Sichuan University
Outcome results
None listed