Cutaneous Melanoma

P2, N=134, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2024 --> Mar 2025

A stage-based follow-up regimen is proposed, which in the experience of the guideline group covers the optimal requirements, although further studies may be considered. This guideline is valid until the end of 2026.

P1, N=5, Active, not recruiting, Case Comprehensive Cancer Center | Phase classification: P1/2 --> P1

P3, N=360, Not yet recruiting, Immatics US, Inc.

P=N/A, N=1000, Recruiting, OHSU Knight Cancer Institute | Not yet recruiting --> Recruiting

P1/2, N=5, Active, not recruiting, Case Comprehensive Cancer Center | Recruiting --> Active, not recruiting | N=15 --> 5

Our findings highlight the critical role of RT-related genes in predicting SKCM prognosis and guiding personalized therapy strategies, particularly in the context of immunotherapy. These contribute to understanding the role of radiotherapy combined with immunotherapy in melanoma.

After the advent of systemic therapies, a trial of the combination targeted therapy of dabrafenib plus trametinib toward BRAF V600-mutant nodal cutaneous melanoma showed that all 35 patients achieved a pathological response...For those tumours that do recur in-field, there are now competing therapies like Talimogene laherparepvec or T-VEC. Generally, ART is now used at the first recurrence. The challenge now is to find which melanomas are truly radiosensitive if ART is to have any future role in this scenario.

P1/2, N=58, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Nov 2025 | Trial primary completion date: Dec 2024 --> Nov 2025

P2, N=220, Active, not recruiting, Agenus Inc. | Suspended --> Active, not recruiting

This cohort study suggests that indoor tanning exposure, while known to increase risk of melanoma, may not be meaningfully associated with melanoma TMB. Additional characteristics were associated with higher TMB and, thus, potentially improved immune checkpoint inhibitor response.

Impaired ImmTAC®-redirected cytotoxicity of exhausted T cells was rescued using an anti-PD-1 antibody, supporting the use of a combination strategy to treat tumors with active PDL1-PD1 axes. Our data demonstrate selective and efficient T cell activation and killing by a PRAME-directed TCRxCD3 bispecific, supporting further investigation in multiple cancer indications.

P1, N=6, Terminated, Mayo Clinic | Trial completion date: Jul 2025 --> Apr 2024 | Active, not recruiting --> Terminated; Lack of funding

In conclusion, we used CRISPR-Cas9 screening to verify the association between molecular subtypes (C1, C2, and C3), immune subtypes (hot and cold), and risk subtypes (high and low) in patients with CM, particularly in distinguishing survival and prognosis. These findings can be used to guide clinical management and immunotherapy of patients with CM.

No abstract available

Tumor-reactive CD8 TILs showed heterogeneous expression of coinhibitory molecules, including KLRC1 (NKG2A), in subpopulations with therapeutic implications. Overall, our study provides a foundation for enhancing the efficacy of immunotherapy in ALM.

P2, N=313, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Oct 2025

P2, N=3, Terminated, Jonsson Comprehensive Cancer Center | N=28 --> 3 | Trial completion date: Jun 2026 --> Nov 2024 | Recruiting --> Terminated | Trial primary completion date: Jun 2025 --> Nov 2024; poor enrollment

Considering the great difficulty in establishing AM cell culture lines, these findings suggest that AM may be more sensitive to microenvironment perturbations than CM. In conclusion, dual FGFR/VEGFR inhibition may be a viable therapeutic strategy that targets the unique biology of AM.

CD73 could be used to predict the prognosis of patients with several cancers. The potential functional mechanism of CD73 involved in cancer progress may not only dependent on its immunomodulatory effects.

P1, N=6, Active, not recruiting, Vastra Gotaland Region | Recruiting --> Active, not recruiting

Through assessment of ADMET properties and binding ability of receptor-ligand, 15 antagonists and 25 agonists of matched drug-like chemicals showed therapeutic effects on target genes. On the basis of causal relationship, docking score and ADMET evaluation, these hit targets and drug-like compounds yield new directions for the development of potent therapeutic agents in melanoma patients.

Utilizing a protein-protein interaction network, we identified the RHO GTPases Activate WASPs and WAVEs pathway as significantly enriched, suggesting the involvement of these DRGs in cancer-related signaling pathways. Collectively, our findings provide novel insights into the molecular mechanisms and clinical implications of DRGs in pan-cancer, highlighting their potential as biomarkers and therapeutic targets for cancer treatment.

ctDNA detection shows promising results in the post-operative setting for identifying cutaneous melanoma patients at the highest risk of relapse and for real-time monitoring of patients' clinical status and treatment response.

Since we found two patients that developed both melanoma and pancreatic cancer, we compared mutation landscape between the two tumors and identified a pathogenic variant in BRCA2 gene. This review gives valuable insights into the genetic underpinnings of melanoma and pancreatic cancer, urging the continued exploration and research of new genetic biomarkers able to identify patients and families at high risk of developing both cancers and to address to screening and to an effective clinical management of the patient.

P2, N=144, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

In this retrospective study, we searched for a gene signature potentially predictive of the response to the addition of cetirizine to checkpoint inhibition (nivolumab or pembrolizumab with or without previous ipilimumab). ICOSLG expression was associated with CD64, a specific marker of M1 macrophages, at baseline in the patient samples who received cetirizine concomitantly with checkpoint inhibitors, but this association was not present in subjects who had not received cetirizine. In conclusion, our results show that the clinical advantage of concomitant treatment with cetirizine during checkpoint inhibition in patients with malignant melanoma is associated with high ICOSLG expression, which could predict the response to immune checkpoint inhibitor blockade.

The CTLA-4 c.-1577 AA genotype was seen as an independent predictor of worse event-free survival and was also associated with higher gene expression, higher cell proliferation, lower cell apoptosis, and higher cell migration. Our data present, for the first time, evidence that CTLA-4 c.-1577G>A alters the risk and clinical aspects of CM treated with conventional procedures and may be used for selecting individuals for tumor prevention and patients for distinct treatment.

P=N/A, N=2998, Recruiting, Melanoma and Skin Cancer Trials Limited | Phase classification: P3 --> P=N/A

P=N/A, N=400, Active, not recruiting, Melanoma and Skin Cancer Trials Limited | Phase classification: P3 --> P=N/A

P1/2, N=29, Completed, Anaveon AG | Recruiting --> Completed | N=130 --> 29 | Trial completion date: Dec 2024 --> Aug 2024

Subsequent knockdown of IL4I1 promoted both the proliferation and inhibited the apoptosis of melanoma cells. In summary, our study identified a series of potential prognostic genes in melanoma and verified the functional role of IL4I1 among them.

P1/2, N=358, Recruiting, GI Innovation, Inc. | N=92 --> 358 | Trial completion date: Jun 2025 --> Apr 2027 | Trial primary completion date: Apr 2025 --> Nov 2025

Insights into TPP1-associated glycans highlighted glycosylated sites contributing to tumorigenesis. This study provides molecular signatures for further functional and therapeutic research on shelterin, highlighting its potential as a target for anti-cancer therapies and promising prospects for cancer prognosis and prediction.

This study revealed the involvement of PGAM1 in the aerobic glycolysis of melanoma, providing novel insights into the molecular mechanisms of melanoma progression.

P2, N=59, Active, not recruiting, Mayo Clinic | Recruiting --> Active, not recruiting | N=30 --> 59

P1, N=20, Suspended, Mayo Clinic | Trial completion date: Oct 2024 --> Jan 2026 | Withdrawn --> Suspended | Trial primary completion date: Oct 2024 --> Jan 2026

This study highlights distinct genetic abnormalities and actionable alterations in Japanese melanoma patients. This suggests a lower tumor mutational burden in East Asian cutaneous melanoma, which may affect the efficacy of immune checkpoint inhibitors. The heterogeneity of driver mutations across and within individuals highlights the need for personalized treatment approaches.

Overall, LINC00094 expression may regulate melanoma cell growth and motility by modulating the expression of miR-1270, and targeting genes of CD276 and CENPM indicating its therapeutic potential in melanoma treatment.

Numb and NumbL were found to inhibit melanoma cell growth by modulating immune cell activity. These results suggested that Numb and NumbL may be potential therapeutic targets for SKCM patient immunotherapy.

P1/2, N=5, Terminated, National Cancer Institute (NCI) | Phase classification: P1 --> P1/2

More data are needed to further understand the role of adjuvant radiotherapy. Molecular markers, such as KIT and BRAF mutations, should be examined.