Uveal Melanoma

P2, N=7, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Jan 2027 --> Dec 2025

P1, N=16, Active, not recruiting, Modulation Therapeutics, Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Mar 2026 --> Mar 2027

Genetic or pharmacological targeting of S100A6-FGFR3 signaling effectively suppressed BAP1-deficient UM metastasis in preclinical models, highlighting the therapeutic potential of targeting this signaling pathway. Overall, our findings establish S100A6 as a critical mediator of hepatic metastasis in BAP1-deficient UM through FGFR3-dependent tumor microenvironment activation, revealing its therapeutic potential.

P1, N=75, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting | Trial completion date: Dec 2025 --> Jun 2027 | Trial primary completion date: Dec 2025 --> Jun 2027

P1, N=17, Completed, H. Lee Moffitt Cancer Center and Research Institute | Active, not recruiting --> Completed

Combined inhibition of LSD1 and PARP1, using SP2509/SP2577 and olaparib, respectively, synergistically hinders NER, induces apoptosis, reduces tumor burden, and prolongs the survival of multiple BAP1-deficient pancancer in vitro models and in vivo xenografts. In conclusion, our results provide a deubiquitination landscape of BAP1; elucidate the mechanisms of action of BAP1, LSD1, and PARP1 in pancancers; and describe a promising combination therapeutic strategy applicable across multiple cancers with BAP1 mutations.

P1, N=210, Active, not recruiting, iOnctura | Trial completion date: Mar 2025 --> Mar 2027

This work establishes cuproptosis induction via NP@Fla-Cu as a transformative strategy against UM, effectively addressing challenges in tumor selectivity and off-target toxicity. The dual functionality of flavopiridol as a copper ionophore and mitophagy activator provides a promising combinatorial approach to overcome therapy resistance in immunosuppressive malignancies.

We differentiated human pluripotent stem cells into the neuronal lineage and depleted BAP1 via doxycycline inducible shRNA...Bulk RNA seq analysis showed that neuronal progenitor and neural crest specific transcripts were reduced while surface ectoderm transcripts were higher in BAP1 depleted cells. Thus, our results clearly demonstrate that BAP1 is required for human neuronal progenitor cell formation, since it regulates neuronal and EMT genes.

P=N/A, N=50, Recruiting, Centre Jean Perrin | Active, not recruiting --> Recruiting | Trial completion date: Oct 2027 --> Apr 2028 | Trial primary completion date: Oct 2026 --> Apr 2028

TILs can be manufactured using the CliniMACS Prodigy. Administration of TIL via HAI was safe and feasible in patients with liver-dominant metastatic uveal melanoma. The used regimen appears insufficient to achieve durable clinical efficacy and implies a need for further testing to obtain conclusive results.

Analysis of microRNA expression levels in the blood plasma of CM patients can be used to assess the effectiveness of brachytherapy and to monitor patients within the framework of lifelong follow-up.