Ocular Melanoma

P2, N=40, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

Topical interferon alpha-2a is safe and effective for treating PAM with atypia and for PAM with atypia surrounding conjunctival melanoma that arises from PAM with atypia, with high response rates and little to no toxicity. Its similarity to IFN α-2b and safety profile make IFN α-2a a good alternative. Further large-scale, controlled studies are needed to validate these findings and their role in clinical practice.

p16INK4a loss involves genomic, epigenetic, and post-translational mechanisms. Restoring p16 function may reduce CJM aggressiveness.

Canonical NF-κB signaling is mechanistically related to UM cell survival, proliferation, and migration, as shown by pharmacologic inhibition like BAY11-7082, and niclosamide and genetic modulation like microRNA-9. NF-κB signaling, particularly the canonical branch, is required for UM malignancy, while noncanonical signaling is linked with high-risk features. Branch-specific genetic manipulations and clinically relevant models should be employed in future research to maximize therapeutic strategies.

Plasma analysis identified a pathogenic SPEN variant and human leukocyte antigen (HLA) genotype (HLA-A*02:17 and HLA-A*02:01 alleles), conferring therapeutic eligibility for tebentafusp, and molecular evidence supportive of metastatic uveal melanoma, enabling initiation of appropriate systemic therapy before additional tissue sampling...While the liquid biopsy and ablation of one of the lesions confirmed the diagnosis, the liquid biopsy was a key first step that provided a comprehensive diagnostic and prognostic picture without the need for an invasive procedure. This case highlights how integrating liquid biopsy into the diagnostic pathway for uveal melanoma can lead to earlier, more informed treatment decisions.

P=N/A, N=10, Not yet recruiting, Massachusetts General Hospital

P2, N=85, Active, not recruiting, iOnctura | Recruiting --> Active, not recruiting

P=N/A, N=100, Not yet recruiting, Aura Biosciences

Histopathology confirmed the diagnosis of teratoid medulloepithelioma in both cases and genetic testing found a germline DICER1 mutation in one of them. These cases highlight the importance of considering medulloepithelioma in the differential diagnosis of intraocular tumours and underscore the value of genetic evaluation for underlying DICER1 mutations.

P2, N=24, Recruiting, Aura Biosciences | Trial completion date: Feb 2027 --> Oct 2027 | Trial primary completion date: Mar 2026 --> Nov 2026

P1, N=17, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Dec 2025 --> Jun 2026

P1, N=12, Terminated, Mayo Clinic | Trial completion date: Jan 2027 --> Sep 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2027 --> Sep 2025; Lack of funding; lack of objective response