Mucosal Melanoma

In summary, targeted sequencing of a large NGS panel can detect predicted ultraviolet radiation mutational signatures in skin cancer with >99% specificity. This preliminary result warrants a potential application of mutational signature characterization in routine tumor profiling testing. Further investigation with larger data sets will follow up to determine the overall sensitivity and specificity for detection.

P=N/A, N=200, Not yet recruiting, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine; Shanghai Ninth People's Hospital, Shanghai Jiaotong University Scho

The histopathologic features of SNMM are quite variable and immunohistochemical analysis is usually necessary for diagnosis. Mucosal melanomas lack ultraviolet signature, have low somatic mutational burden, and are reported to have more genomic instability manifested as structural variants, deletions, and amplifications.

P1/2, N=264, Recruiting, Perspective Therapeutics | Trial completion date: Jun 2027 --> Dec 2029 | Trial primary completion date: Jun 2025 --> Dec 2027

P3, N=1535, Recruiting, Regeneron Pharmaceuticals | Trial completion date: Aug 2032 --> Jun 2031 | Trial primary completion date: Mar 2026 --> Jun 2025

P1, N=70, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting | N=50 --> 70

Finally, we identify an immune-suppressive stromal signature in a subset of CMM characterised by the downregulation of key immune checkpoints and pathways. Together, these findings provide a solid foundation for understanding the role of CAS in canine melanoma, specific to cutaneous and mucosal subtypes.

These mutations were categorized based on the gene functions. The identification of these mutations provides critical insights that can pave the way for the development of novel therapeutic strategies for both canine and human OMM, offering hope for more effective treatments in the future.

HBM4003 0.3 mg/kg plus toripalimab 240 mg every 3 week demonstrated manageable safety in solid tumors and no new safety signal. Limited data demonstrated promising antitumor activity, especially in PD-1 treatment-naïve mucosal melanoma.

In assessing if a CM gene expression panel could aid in the risk stratification of patients with CJM, we found that the uveal melanoma-relevant gene, BAP1, may be important. Additional studies with larger sample sizes are needed to determine the relevance of this and other differentially expressed genes in CJM prognostication.

P2, N=56, Active, not recruiting, Istari Oncology, Inc. | Trial primary completion date: Jun 2024 --> Oct 2024

P1/2, N=264, Recruiting, Perspective Therapeutics | N=52 --> 264

Vulvar melanoma is the third tumor to have been reported to harbor TRIM33::CSDE1 fusion. Detecting fusions may have a clinically significant impact in patients with advanced mucosal melanoma who have failed front-line immunotherapy.

The results of our study suggest that neuroendocrine differentiation is not uncommon in oral and sinonasal melanomas. Knowing that malignant melanomas can show neuroendocrine differentiation will prevent diagnostic pitfalls.

The distinct genomic profiling in Japanese patients, including lower TMB, compared to Caucasians, is associated with poorer treatment outcomes. This result underscores the need for more effective therapeutic agents.

CASP8 alterations are the earliest driving events in oral field carcinogenesis, whereas additional somatic mutational, copy number and transcriptomic alterations ultimately lead to OSCC tumour formation and progression.

However, an elevated LDH is a reliable, independent negative prognostic marker. Inter-disciplinary management remains essential in order to develop optimal treatment strategies.

This study identifies eosinophils, macrophages, natural killer cells and plasma cells as favorable prognostic factors. Therefore, a CD8:CD4 ratio of more than 3 is correlated with a good response to PD-1 inhibitor therapy.

P=N/A, N=65, Completed, CHU de Reims | Unknown status --> Completed

P1/2, N=202, Recruiting, BeiGene | Trial completion date: Aug 2025 --> Sep 2026 | Trial primary completion date: Sep 2024 --> Apr 2026

P1, N=45, Recruiting, Centre hospitalier de l'Université de Montréal (CHUM) | Trial primary completion date: Apr 2024 --> Apr 2025

P1, N=43, Completed, Mayo Clinic | N=73 --> 43

P1/2, N=0, Withdrawn, Immunocore Ltd | N=113 --> 0 | Completed --> Withdrawn

P1, N=73, Completed, Mayo Clinic | Active, not recruiting --> Completed | Trial completion date: Jun 2025 --> Jul 2024

P1, N=20, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Nov 2025 --> Nov 2026 | Trial primary completion date: Nov 2024 --> Nov 2025

In contrast, PRKDC may reduce the sensitivity of melanoma patients to immunotherapy by promoting DNA repair in melanoma cells. These results emphasize the clinical value of multi-omics data and have the potential to improve the understanding of melanoma treatment.

P2, N=70, Active, not recruiting, ImaginAb, Inc. | Recruiting --> Active, not recruiting

The most common genetic abnormalities detected in this study occurred in the TERT promoter (TERTp) (n = 5), a finding that has been reported to be associated with aggressive disease. Our data shows that while HPV+ melanoma is rare, identifying this disease entity could help guide therapy given the demonstrated genomic alterations.

Although the clinicians emphasised the necessity of systemic chemotherapy and immunotherapy with the patient and his family, the patient did not receive any adjuvant therapy and died 36 months after surgery. Primary malignant melanoma of GEJ should be considered in a differential diagnosis for gastrointestinal malignancies, especially after excluding the source of metastasis through a systemic examination.

We identified high densities of TIM-3+ and TIGIT+ TILs as strong negative prognostic biomarkers in SNMM. This suggests that TIM-3 and TIGIT contribute to immunosuppression in SNMM and provides a rationale for novel treatment strategies based on this next generation of immune checkpoint inhibitors. Prospective studies with larger case numbers are warranted to confirm our findings and their implications for immunotherapy.

While known prognostic factors such as TERT promoter mutations and TMB were equally distributed among patients who received either anti-CTLA4 plus anti-PD1 combination therapy or anti-PD1 monotherapy as first line therapy, we did not find a prolonged mPFS or mOS in either of those. For both therapy concepts, mPFS and mOS were considerably shorter than reported for melanomas with known oncogene mutations.

P2, N=54, Recruiting, University Health Network, Toronto | Initiation date: May 2024 --> Jul 2024

P1; Trial completion date: Apr 2024 --> Mar 2025 | Trial primary completion date: Sep 2023 --> Mar 2025

P=N/A, N=14, Active, not recruiting, Centre Francois Baclesse | Recruiting --> Active, not recruiting | N=50 --> 14 | Trial completion date: Nov 2028 --> May 2027 | Trial primary completion date: Nov 2028 --> May 2027

P=N/A, N=17, Completed, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine; Shanghai Ninth People's Hospital, Shanghai Jiaotong University Scho | Recruiting --> Completed

Other alterations, including MYC and CRKL amplifications, were unique to A/M melanomas and susceptible to indirect targeting using the BRD4 inhibitor JQ1 or Src/ABL inhibitor dasatinib, respectively. We further identified new, actionable A/M-specific alterations, including an inactivating NF2 fusion in a mucosal melanoma responsive to dasatinib in vivo. Our study highlights new molecular differences between cutaneous and A/M melanomas, and across different anatomic sites within A/M, which may change clinical testing and treatment paradigms for these rare melanomas.

Desmoplastic melanoma, a high-risk cutaneous melanoma, is associated with high locoregional recurrence rates and mutational burden, suggesting this melanoma may have enhanced response to immunotherapy. While these variants of melanoma represent distinct disease entities, this review highlights the clinicopathologic characteristics and treatment recommendations for each of these rare melanomas and highlights the utility of modern therapies for each of them.

This technique offers a minimally invasive means to obtain cell samples, particularly beneficial for patients that are ineligible for surgical procedures, and enables the establishment of in vitro models crucial for comparative studies in mucosal melanoma oncology. To the best of our knowledge, this is the first work establishing neoplastic primary cell cultures via fine-needle aspiration in dogs.

Axitinib with anti-PD-1 therapy has modest clinical activity in heavily pretreated patients with mucosal melanoma outside of Asia, including some with long-term benefits. This data supports the worldwide clinical trials evaluating this combination and the role of incorporating vascular endothelial growth factor-based therapy in the therapeutic paradigm for patients with mucosal melanoma.

P2, N=180, Recruiting, Mural Oncology, Inc | Trial completion date: Sep 2025 --> Sep 2026 | Trial primary completion date: Mar 2024 --> Jun 2025

P1/2, N=30, Recruiting, University of Colorado, Denver | Trial primary completion date: Jul 2024 --> Jul 2025

P2, N=0, Withdrawn, Melanoma Institute Australia | N=44 --> 0 | Not yet recruiting --> Withdrawn