Au-TMP and Radiotherapy for Advanced Melanoma With Anti-PD-1 Therapy
ConditionAdvanced Melanoma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorWest China Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age: Age ≥ 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
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.
Presence of at least one measurable lesion according to RECIST v1.1 criteria.
Disqualifiers
Prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents.
Known hypersensitivity to recombinant humanized anti-PD-1 monoclonal antibodies or any of their components.
Active skin breakdown, infection, ulceration, necrosis, bleeding at the injection site, or a high risk of hollow organ perforation.
Known allergy or intolerance to Au-TMP active ingredients, excipients, or similar compounds.
Trial design
Design model
Single group
Treatments tested in this trial
Au-TMP
DrugA single intratumoral injection of Au-TMP (at concentrations of 50 mg/mL using escalating dose levels of 5% or 10% of tumor volume)
Fractionated Radiotherapy (RT)
RadiationLocal radiotherapy (RT) delivered to the injected tumor lesion, with a total dose of 30 Gy delivered in 5 fractions (6 Gy per fraction).
Toripalimab
DrugAdministration of Toripalimab (anti-PD-1 antibody) at a fixed dose of 240 mg, administered every 2 weeks (Q2W).
Treatment groups
6 Participants
are divided into 1 treatment groupGroup A: Au-TMP Plus Radiotherapy and ToripalimabExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
Incidence of Dose-Limiting Toxicities (DLTs)
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.
Time frame
From the administration of Au-TMP (Day 1) through Day 28.Secondary outcomes
1
Incidence and Severity of Adverse Events (AEs)
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.
Time frame
Up to 12 months from the date of Au-TMP administration.2
Pharmacokinetic (PK) Parameters
Concentration-time curves and related PK parameters of gold (Au) elements in whole blood, plasma, and urine following intratumoral injection of Au-TMP.
Time frame
Day 1 (pre-injection, 1h, 2h, 4h, 8h, 24h post-injection), and Days 4, 8, 15, 28.3
Objective Response Rate (ORR)
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 \[with immune-modified RECIST (iRECIST) criteria as a secondary reference\].
Time frame
Baseline up to disease progression or up to 12 months from the date of Au-TMP administrationOther outcomes
1
Progression-Free Survival (PFS) and Overall Survival (OS)
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.
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)2
Peripheral blood immune microenvironment changes
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)).
Time frame
Up to 3 months from the date of Au-TMP administrationSponsors and contacts
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Source ClinicalTrials.gov