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

Summary

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.

Timeline

Start

2026-04-28

Primary completion

2028-04-30

Completion

2029-04-30

Publications

• Background Bonvalot S, Rutkowski PL, Thariat J, Carrere S, Ducassou A, Sunyach MP, Agoston P, Hong A, Mervoyer A, Rastrelli M, Moreno V, Li RK, Tiangco B, Herraez AC, Gronchi A, Mangel L, Sy-Ortin T, Hohenberger P, de Baere T, Le Cesne A, Helfre S, Saada-Bouzid E, Borkowska A, Anghel R, Co A, Gebhart M, Kantor G, Montero A, Loong HH, Verges R, Lapeire L, Dema S, Kacso G, Austen L, Moureau-Zabotto L, Servois V, Wardelmann E, Terrier P, Lazar AJ, Bovee JVMG, Le Pechoux C, Papai Z. NBTXR3, a first-in-class radioenhancer hafnium oxide nanoparticle, plus radiotherapy versus radiotherapy alone in patients with locally advanced soft-tissue sarcoma (Act.In.Sarc): a multicentre, phase 2-3, randomised, controlled trial. Lancet Oncol. 2019 Aug;20(8):1148-1159. doi: 10.1016/S1470-2045(19)30326-2. Epub 2019 Jul 8.
• Background Zhang Y, Huang F, Ren C, Liu J, Yang L, Chen S, Chang J, Yang C, Wang W, Zhang C, Liu Q, Liang XJ, Liu J. Enhanced Radiosensitization by Gold Nanoparticles with Acid-Triggered Aggregation in Cancer Radiotherapy. Adv Sci (Weinh). 2019 Jan 8;6(8):1801806. doi: 10.1002/advs.201801806. eCollection 2019 Apr 17.
• Background Jiang Y, Cao H, Deng H, Guan L, Langthasa J, Colburg DRC, Melemenidis S, Cotton RM, Aleman J, Wang XJ, Graves EE, Kalbasi A, Pu K, Rao J, Le QT. Gold-siRNA supraclusters enhance the anti-tumor immune response of stereotactic ablative radiotherapy at primary and metastatic tumors. Nat Biotechnol. 2025 Sep;43(9):1496-1509. doi: 10.1038/s41587-024-02448-0. Epub 2024 Oct 24.
• Background Gorodetska I, Schulz A, Behre G, Dubrovska A. Confronting Melanoma Radioresistance: Mechanisms and Therapeutic Strategies. Cancers (Basel). 2025 Aug 14;17(16):2648. doi: 10.3390/cancers17162648.
• Background Zhao Y, Zhang T, Wang Y, Lu D, Du J, Feng X, Zhou H, Liu N, Zhu H, Qin S, Liu C, Gao X, Yang Z, Liu Z. ICAM-1 orchestrates the abscopal effect of tumor radiotherapy. Proc Natl Acad Sci U S A. 2021 Apr 6;118(14):e2010333118. doi: 10.1073/pnas.2010333118.
• Background Sheng X, Huang G, Fang M, Li K, Wu D, Zhang X, Chen J, Zhu D, Chen Y, Li H, Gao Q, Wu L, Tang B, Yan X, Zeng R, Li J, Yu W, Xu J, Hao Y, Jin C, Zou J, Guo J. Toripalimab vs Dacarbazine as First-Line Therapy for Advanced Melanoma of Acral Subtype: The Phase 3 MELATORCH Randomized Clinical Trial. JAMA Oncol. 2026 Mar 1;12(3):243-250. doi: 10.1001/jamaoncol.2025.5751.
• Background Jalil A, Donate MM, Mattei J. Exploring resistance to immune checkpoint inhibitors and targeted therapies in melanoma. Cancer Drug Resist. 2024 Oct 31;7:42. doi: 10.20517/cdr.2024.54. eCollection 2024.
• Background Seth R, Agarwala SS, Messersmith H, Alluri KC, Ascierto PA, Atkins MB, Bollin K, Chacon M, Davis N, Faries MB, Funchain P, Gold JS, Guild S, Gyorki DE, Kaur V, Khushalani NI, Kirkwood JM, McQuade JL, Meyers MO, Provenzano A, Robert C, Santinami M, Sehdev A, Sondak VK, Spurrier G, Swami U, Truong TG, Tsai KK, van Akkooi A, Weber J. Systemic Therapy for Melanoma: ASCO Guideline Update. J Clin Oncol. 2023 Oct 20;41(30):4794-4820. doi: 10.1200/JCO.23.01136. Epub 2023 Aug 14.
• Background Chinese guidelines for diagnosis and treatment of melanoma 2018 (English version). Chin J Cancer Res. 2019 Aug;31(4):578-585. doi: 10.21147/j.issn.1000-9604.2019.04.02. No abstract available.
• Background Chi Z, Li S, Sheng X, Si L, Cui C, Han M, Guo J. Clinical presentation, histology, and prognoses of malignant melanoma in ethnic Chinese: a study of 522 consecutive cases. BMC Cancer. 2011 Feb 25;11:85. doi: 10.1186/1471-2407-11-85.
• Background Okobi OE, Abreo E, Sams NP, Chukwuebuni OH, Tweneboa Amoako LA, Wiredu B, Uboh EE, Ekechi VC, Okafor AA. Trends in Melanoma Incidence, Prevalence, Stage at Diagnosis, and Survival: An Analysis of the United States Cancer Statistics (USCS) Database. Cureus. 2024 Oct 2;16(10):e70697. doi: 10.7759/cureus.70697. eCollection 2024 Oct.
• Background Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024 Jan-Feb;74(1):12-49. doi: 10.3322/caac.21820. Epub 2024 Jan 17.

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