Au-TMP and Radiotherapy for Advanced Melanoma With Anti-PD-1 Therapy

May 1, 2026 updated by: Xingchen Peng, West China Hospital

Safety and Tolerability of Au-TMP Nanoparticles in Combination With Radiotherapy for Patients With Advanced Melanoma Receiving Anti-PD-1 Therapy

Advanced melanoma is a highly aggressive malignancy that frequently exhibits resistance to conventional radiotherapy and single-agent immunotherapy. This study aims to evaluate the safety and tolerability of an innovative melanoma-specific aggregable gold nanosystem (Au-TMP) in patients with advanced melanoma. This single-arm, open-label, Phase 1a clinical trial utilizes a dose-escalation design, where participants receive a single intratumoral injection of Au-TMP followed by sequential radiotherapy and Toripalimab (anti-PD-1) treatment. This trial aims at assessing the safety of intratumoral injection of Au-TMP and radiotherapy in combination with anti-PD-1 therapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Overcoming radioresistance and enhancing the clinical efficacy of immune checkpoint inhibitors remain significant challenges in the treatment of advanced melanoma. Au-TMP nanoparticles serve as an innovative radiosensitizing platform engineered based on the specific enzymatic characteristics of the melanoma microenvironment, enabling in situ aggregation and prolonged intratumoral retention to significantly amplify the local cytotoxic effects of radiation through physical energy deposition. This study employs a scientifically structured sequential administration protocol: an ultrasound- or Computed Tomography (CT)-guided intratumoral injection, fractionated radiotherapy (30 Gy in 5 fractions), and commencement of systemic anti-PD-1 therapy. This regimen is designed to facilitate the capture of tumor-associated antigens by Au-TMP and induce immunogenic cell death (ICD), thereby potentially reversing the immunosuppressive microenvironment. Ultimately, this research aims to evaluate the safety and tolerability of this combination approach while assessing preliminary clinical efficacy in patients with advanced melanoma.

Study Type

Interventional

Enrollment (Estimated)

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Xingchen Peng, Professor
  • Phone Number: +8618980606753
  • Email: pxx2014@163.com

Study Contact Backup

Study Locations

  • China
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • Recruiting
        • West China Hospital, Sichuan University
        • Contact:
      • Chengdu, Sichuan, China, 610041
        • Not yet recruiting
        • West China Hospital, Sichuan University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age: Age ≥ 18 years.
  2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  3. Histologically confirmed unresectable Stage III or Stage IV melanoma without prior systemic therapy. Prior adjuvant or neoadjuvant therapy is permitted, provided it was completed at least 3 weeks before enrollment and all related adverse events (AEs) have resolved to baseline or NCI CTCAE v5.0 Grade ≤ 1.
  4. Presence of at least one measurable lesion according to RECIST v1.1 criteria.
  5. At least one lesion suitable for intratumoral injection and radiotherapy (located in the skin, subcutaneous tissue, superficial lymph nodes, or visceral lesions assessed as safe for access) that has not received prior radiotherapy (unless documented progression has occurred).

  6. Adequate hematologic and organ function within 7 days prior to the first dose, including:

    Hematology: Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L; Platelet count (PLT) ≥ 90 × 10⁹/L; Hemoglobin (Hb) ≥ 90 g/L. (No Granulocyte-Colony Stimulating Factor (G-CSF), platelet transfusion, or Erythropoietin (EPO)/Red Blood Cell (RBC) transfusion within 14 days prior to testing).

    Renal Function: Serum creatinine (Cr) ≤ 1.5 × Upper Limit of Normal (ULN), or calculated creatinine clearance (Ccr) ≥ 50 mL/min using the Cockcroft-Gault formula.

    Hepatic Function: Total bilirubin (TBIL) ≤ 1.5 × ULN (≤ 3.0 × ULN for patients with Gilbert's Syndrome or liver metastases); Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and Alkaline Phosphatase (ALP) ≤ 2.5 × ULN (≤ 5.0 × ULN for patients with documented liver or bone metastases); Serum albumin ≥ 2.8 g/dL.

    Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT) ≤ 1.5 × ULN.

    Cardiac: Left Ventricular Ejection Fraction (LVEF) ≥ 50%.

  7. Anticipated survival time ≥ 16 weeks.
  8. Agreement to use highly effective contraception methods during the trial and for 12 months after the last dose of treatment.
  9. Voluntarily participate in the study, sign the Informed Consent Form (ICF), demonstrate good compliance, and be willing to cooperate with follow-up.

Exclusion Criteria:

  1. Prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents.
  2. Known hypersensitivity to recombinant humanized anti-PD-1 monoclonal antibodies or any of their components.
  3. Active skin breakdown, infection, ulceration, necrosis, bleeding at the injection site, or a high risk of hollow organ perforation.
  4. Known allergy or intolerance to Au-TMP active ingredients, excipients, or similar compounds.
  5. Presence of known driver mutations (e.g., BRAF V600E/K, c-KIT, NRAS) for which targeted therapies are already approved and available as first-line treatment.
  6. Ocular (uveal) or mucosal melanoma.
  7. Receipt of other anti-tumor therapies (including corticosteroids or immunotherapy) or participation in other clinical trials within 4 weeks before treatment initiation; failure to recover from toxicities of prior therapies (except Grade 2 alopecia and Grade 1 neurotoxicity).
  8. Pregnant or breastfeeding women.
  9. Positive for Human Immunodeficiency Virus (HIV) or Hepatitis C Virus (HCV). Patients with positive Hepatitis B Surface Antigen (HBsAg) or Hepatitis B Core Antibody (HBcAb) must have a negative Hepatitis B Virus (HBV) DNA test (quantitative detection < 500 IU/mL).
  10. History of active tuberculosis.
  11. Active autoimmune disease requiring systemic treatment within the past 2 years (except physiological replacement therapy for thyroid, insulin, or adrenal/pituitary insufficiency).
  12. Serious uncontrolled concurrent medical conditions, including uncontrolled diabetes, interstitial lung disease, New York Heart Association (NYHA) Class III/IV heart failure, severe cardiac arrhythmias, or recent (within 6 months) myocardial infarction or cerebrovascular accidents.
  13. Active Central Nervous System (CNS) or leptomeningeal metastases. Patients with treated brain metastases are eligible if they are stable (no progression via Magnetic Resonance Imaging (MRI)) for at least 8 weeks post-treatment and 28 days prior to the first dose, and do not require immunosuppressive doses of corticosteroids (>10 mg/day prednisone equivalent) for at least 2 weeks.
  14. Receipt of hematopoietic stimulants (e.g., G-CSF, EPO) within 2 weeks prior to treatment.
  15. Receipt of live vaccines within 4 weeks prior to treatment.
  16. Major surgery (excluding diagnostic procedures) within 4 weeks prior to treatment.
  17. History of psychiatric disorders or persistent drug/substance abuse.
  18. Other malignancies within the past 5 years, except for successfully treated localized cancers such as basal/squamous cell skin cancer or in situ carcinomas (cervix, breast, prostate).
  19. Any other acute or chronic medical/psychiatric condition or laboratory abnormality that, in the investigator's opinion, increases research-related risk or interferes with the interpretation of study results.
  20. Any condition that is not in the best interest of the participant.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Au-TMP Plus Radiotherapy and Toripalimab
Patients receive a single intratumoral injection of Au-TMP followed by radiotherapy and systemic Toripalimab.
Drug: Au-TMP
A single intratumoral injection of Au-TMP (at concentrations of 50 mg/mL using escalating dose levels of 5% or 10% of tumor volume)
Drug: Toripalimab
Administration of Toripalimab (anti-PD-1 antibody) at a fixed dose of 240 mg, administered every 2 weeks (Q2W).
Radiation: Fractionated Radiotherapy (RT)
Local radiotherapy (RT) delivered to the injected tumor lesion, with a total dose of 30 Gy delivered in 5 fractions (6 Gy per fraction).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Dose-Limiting Toxicities (DLTs)
Time Frame: From the administration of Au-TMP (Day 1) through Day 28.
DLT is defined as any toxicity event occurring within the DLT observation period (from the day of Au-TMP intratumoral injection to Day 28) that is judged by the investigator to be related (possibly, probably, or definitely related) to Au-TMP and meets the pre-specified DLT criteria defined in the protocol.
From the administration of Au-TMP (Day 1) through Day 28.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetic (PK) Parameters
Time Frame: Day 1 (pre-injection, 1h, 2h, 4h, 8h, 24h post-injection), and Days 4, 8, 15, 28.
Concentration-time curves and related PK parameters of gold (Au) elements in whole blood, plasma, and urine following intratumoral injection of Au-TMP.
Day 1 (pre-injection, 1h, 2h, 4h, 8h, 24h post-injection), and Days 4, 8, 15, 28.
Incidence and Severity of Adverse Events (AEs)
Time Frame: Up to 12 months from the date of Au-TMP administration.
Incidence, severity, and causality of Adverse Events (AEs), Treatment-Emergent Adverse Events (TEAEs), Grade ≥3 Treatment-Related Adverse Events (TRAEs), and Serious Adverse Events (SAEs). All events are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.
Up to 12 months from the date of Au-TMP administration.
Objective Response Rate (ORR)
Time Frame: Baseline up to disease progression or up to 12 months from the date of Au-TMP administration
The proportion of participants who achieve a Complete Response (CR) or Partial Response (PR), assessed based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria [with immune-modified RECIST (iRECIST) criteria as a secondary reference].
Baseline up to disease progression or up to 12 months from the date of Au-TMP administration

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS) and Overall Survival (OS)
Time Frame: From the date of Au-TMP administration until the date of first documented progression or death from any cause (up to 2 years)
PFS is defined as the time from Au-TMP administration to the first documented disease progression (PD) according to RECIST v1.1, or death due to any cause, whichever occurs first. OS is defined as the time from Au-TMP administration to death from any cause. For participants who are still alive at the end of the study, data will be censored at the last known date of follow-up.
From the date of Au-TMP administration until the date of first documented progression or death from any cause (up to 2 years)
Peripheral blood immune microenvironment changes
Time Frame: Up to 3 months from the date of Au-TMP administration

Treatment-related dynamic changes in peripheral blood immune microenvironment, including:

Frequency, absolute count, phenotype (activation/exhaustion markers), and functional status of key immune cell subsets (e.g., Cluster of Differentiation 8-positive (CD8+) T cells); Levels of relevant cytokines (e.g., Interferon-gamma (IFN-γ), Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6)).
Up to 3 months from the date of Au-TMP administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

West China Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 28, 2026

Primary Completion (Estimated)

April 30, 2028

Study Completion (Estimated)

April 30, 2029

Study Registration Dates

First Submitted

April 24, 2026

First Submitted That Met QC Criteria

April 24, 2026

First Posted (Actual)

May 1, 2026

Study Record Updates

Last Update Posted (Actual)

May 7, 2026

Last Update Submitted That Met QC Criteria

May 1, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026-811

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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