Mucosal Melanoma

This study clarified the genetic differences between OMM and NMM, and the first to report the frequent occurrence of RICTOR amplification in OMM. This analysis offers insights into the development of personalized therapeutics for OMM.

P2, N=80, Recruiting, ImaginAb, Inc. | Phase classification: P2b --> P2 | Trial completion date: Dec 2025 --> Jul 2025 | Trial primary completion date: Dec 2024 --> Jul 2025

P=N/A, N=80, Recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2026 --> Jul 2029 | Trial primary completion date: Dec 2026 --> Jul 2029

Finally, tumor escalation pathways proved consistent with immune evasion, with immune-related pathways becoming significantly downregulated. To our knowledge, it is previously unreported that these critical milestones needed for KIT-driven melanoma tumor formation have been studied at the molecular level using isogenically matched and phenotypically defined cells.

P2, N=72, Active, not recruiting, National Cancer Institute (NCI)

P2, N=56, Active, not recruiting, Istari Oncology, Inc. | Trial completion date: Oct 2023 --> Oct 2024 | Trial primary completion date: Oct 2023 --> Jun 2024

P2, N=14, Terminated, Georgetown University | Unknown status --> Terminated; Lack of Enrollment

P2, N=92, Recruiting, Providence Health & Services | Not yet recruiting --> Recruiting

P1, N=30, Recruiting, Dana-Farber Cancer Institute | N=20 --> 30

Ethnicity and melanoma subtype are associated with survival and recurrence pattern in melanoma patients treated with adjuvant anti-PD-1. Toxicity profile differs by ethnicity and may require a precision toxicity surveillance strategy.

P2, N=54, Recruiting, University Health Network, Toronto

This divergence in mutational patterns may partially account for the relatively poorer prognosis, particularly to immune checkpoint inhibitors. This review explores various aspects of acral and mucosal melanoma, including their clinical presentation, pathologic features, mutational profiles, current therapeutic approaches, outcomes associated with systemic therapy, and potential strategies to address resistance to existing treatments.

Resistance to combo nivolumab-ipilimumab demands the application of novel approaches to go with ICIs in melanoma immunotherapy. Immunogenic agents, alternative immune checkpoints, vaccination, oncolytic viruses, extracellular vesicles (EVs) and fecal microbiome transplantation (FMT) are novel strategies in patients developing ICI resistance.

P2, N=99, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

P2, N=31, Active, not recruiting, Yana Najjar | Recruiting --> Active, not recruiting | Trial completion date: Jul 2026 --> Feb 2029

P1/2, N=32, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Apr 2024 --> Apr 2025 | Trial primary completion date: Apr 2024 --> Apr 2025

P1/2, N=115, Recruiting, Medicenna Therapeutics, Inc. | Trial primary completion date: Sep 2024 --> Jun 2026

P1, N=25, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Jan 2024 --> Aug 2024

P2, N=44, Not yet recruiting, Melanoma Institute Australia | Trial completion date: Oct 2030 --> May 2036 | Trial primary completion date: Dec 2025 --> May 2026

P1/2, N=224, Recruiting, Ascentage Pharma Group Inc. | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=94, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Aug 2023 --> Dec 2024 | Trial primary completion date: Mar 2022 --> Sep 2023

P2/3, N=1925, Recruiting, Regeneron Pharmaceuticals | Phase classification: P3 --> P2/3 | Trial completion date: Apr 2031 --> Aug 2032

Emerging immunotherapies, including T-cell-based therapies and vaccines targeting PRAME, are being investigated to exploit its cancer-specific expression. Ongoing research into the molecular role and mechanism of action of PRAME in skin cancer continues to open new avenues in both diagnostics and therapeutics, with the potential to transform the management of melanoma and related skin cancers.

Ipilimumab plus nivolumab has achieved the best median overall survival, exceeding 70 months. However, the introduction of new ICIs, like relatlimab, has added complexity to first-line therapy decisions...We also provide the latest insights into the treatment of rare melanoma subtypes, such as uveal melanoma, where tebentafusp has shown promising improvements in overall survival for metastatic uveal melanoma patients. This review provides invaluable insights for clinicians, enabling informed treatment choices and deepening our understanding of the multifaceted challenges associated with advanced melanoma management.

The findings from this study could contribute to the development of new diagnosis and treatment strategies for this rare and aggressive cancer. Future research directions may include investigating other possible pathways involved in melanoma progression.

Performing radiotherapy may have a protective effect on OS for head and neck MM. New treatment strategies are urgently needed to improve the outcome in this disease.

P2, N=42, Active, not recruiting, Highlight Therapeutics | Trial completion date: Dec 2023 --> Aug 2024

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

P2, N=92, Not yet recruiting, Providence Health & Services | Trial completion date: Dec 2030 --> Feb 2030 | Trial primary completion date: Dec 2028 --> Feb 2028

P1/2, N=113, Completed, Immunocore Ltd | Phase classification: P1b/2 --> P1/2

P2; N=15 --> 0 | Recruiting --> Withdrawn

Although limited by sample size and follow-up, these findings highlight the potential of the combination of ziv-aflibercept antiangiogenic therapy with pembrolizumab in patients with advanced melanoma resistant to anti-PD-1 treatment and the need for further research to improve outcomes in anti-PD-1-resistant melanoma.

Overall, these novel and unique cellular systems represent relevant experimental tools for a better understanding of the biology of these neoplasms and, as an extension, to MM from other sites.

Cases with BRAF or c-KIT mutations may be considered for targeted therapies. Unfortunately, MM prognosis remains unfavorable, with a less than 50% survival rate at 2 years.

P2, N=31, Recruiting, Yana Najjar | Trial completion date: Dec 2025 --> Jul 2026 | Trial primary completion date: Sep 2023 --> Apr 2024

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

P2, N=44, Not yet recruiting, Melanoma Institute Australia

P2, N=92, Not yet recruiting, Providence Health & Services

Therefore, this review seeks to address this deficiency by offering a novel and thorough analysis of the current status, potential resistance mechanisms, and future prospects of applying ICIs specifically to oral malignant melanoma. Clarifying and thoroughly understanding these mechanisms will facilitate the advancement of effective therapeutic approaches and enhance the prospects for patients suffering from oral mucosal melanoma.

Conclusion  This constitutes one of the few reports on comprehensive analysis of molecular alterations underlying melanomas in Indian patients. A larger sample size, with more extensive molecular markers, would yield additional information on the disease manifestation.

P2, N=99, Suspended, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P3, N=1345, Active, not recruiting, National Cancer Institute (NCI)