P1/2, N=54, Not yet recruiting, M.D. Anderson Cancer Center

P1/2, N=727, Recruiting, Immunocore Ltd | N=170 --> 727 | Trial completion date: Feb 2026 --> Jun 2026 | Trial primary completion date: Feb 2024 --> Jun 2026

PRAME is a useful marker for the diagnosis of melanoma in cytology material, but it is less sensitive than SOX10. PRAME is also expressed in other nonmelanocytic tumors which limits its specificity.

P1, N=45, Active, not recruiting, CRISPR Therapeutics AG | Recruiting --> Active, not recruiting

P3, N=680, Recruiting, Immunocore Ltd | Not yet recruiting --> Recruiting

GEP agreed with the final diagnosis in 88% of cases with a sensitivity of 65%, 97% specificity, and positively predicted melanoma in 91.7% of cases. Because the results of this study align with past publications evaluating the performance metrics of PRAME IHC, showing it to be as sensitive as and more cost effective than all other ancillary molecular tests, we propose the use of PRAME IHC as the optimal first-line diagnostic tool for ambiguous melanocytic proliferations.

P1/2, N=22, Active, not recruiting, NexImmune Inc. | Recruiting --> Active, not recruiting | Trial completion date: Mar 2023 --> Mar 2025 | Trial primary completion date: Oct 2022 --> Oct 2024

Therefore, PRAME expression may serve as a useful marker for CIS of the urinary tract. Furthermore, PRAME may be a candidate for the novel therapeutic target for standard treatment-refractory CIS patients.

Our results further support PRAME overexpression in gynecologic cancers, including CS with similar expression levels in epithelial and mesenchymal components. PRAME might have a role in epithelial-mesenchymal transition in this group of cancers.

P3, N=680, Not yet recruiting, Immunocore Ltd

P1/2, N=4, Terminated, Bellicum Pharmaceuticals | N=28 --> 4 | Unknown status --> Terminated; company decision

No abstract available

No abstract available

No abstract available

Oral azacytidine may be used as maintenance treatment in AML in first remission, but can be associated with substantial side effects, and less toxic strategies should be explored. OS at five years was 75% (95% CI: 50-89), with 70% of patients ≥60 years of age being long-term survivors. Maintenance therapy with this DC vaccine was well tolerated in AML patients in CR1 and was accompanied by encouraging 5-year long-term survival.

P1, N=44, Recruiting, Baylor College of Medicine | Trial primary completion date: Apr 2023 --> Apr 2024

P1, N=11, Terminated, Mana Therapeutics | N=27 --> 11 | Active, not recruiting --> Terminated; Product manufacturing

No abstract available

P1, N=107, Active, not recruiting, CRISPR Therapeutics AG | Recruiting --> Active, not recruiting

Early results indicate that the antigen-specific NEXI-001 T cells have the potential to enhance GvL effects and is tolerated with easily manageable side effects. Greater clinical activity has been observed with increased doses of the NEXI-001 T cells. The trial remains ongoing, and the data support an Expansion Cohort of the study that will allow for a more complete assessment of clinical activity.

Among tumors with retained BAP1 staining, PRAME positivity was associated with shorter MFS and DSS (P = .001 and P = .021, respectively). In summary, a combination of BAP1 and PRAME IHC can be used for risk stratification of UMs.

This means a better differential diagnosis, a reliable early diagnosis and a proper clinical/surgical management of the oncological lesions. In conclusion, PRAME can be a valid qualitative marker for differential diagnosis, not only in cutaneous melanomas, but also in malignant melanoma of the entire head and neck area.

Moreover, PRAME played the role at least partially by activating PI3K/AKT/mTOR pathways. The above findings elucidate that PRAME may be a valuable oncogene target, contributing to the diagnosis and therapy of LSCC.

Our study supports the ancillary value of PRAME for diagnosing ALMIS and SMIS with high sensitivity and specificity.

These results suggest the PLA performs as expected in FP IV-VI and that melanin content does not influence assay performance, or the ability of the test to generate a result. Self-collection of samples appears similar to clinician collected samples with respect to pre-test quality assessment.

The results indicate that PRAMEY may play a role in anti-polyspermy defense. This study thus provides the initial evidence for the involvement of the PRAME protein family in sperm function and fertilization.

P1/2, N=9, Terminated, Medigene AG | N=92 --> 9 | Trial completion date: Apr 2024 --> Jul 2022 | Recruiting --> Terminated | Trial primary completion date: Aug 2020 --> Jun 2022; The clinical trial is terminated after the completion of phase I without moving to Phase II.

Treatment was conducted with MDG1011 after lymphodepletion with fludarabine (25 mg/m² x 3d) and cyclophosphamide (300 mg/m² x 3d) in patients with HLA-A*02:01- and PRAME-positive r/r disease...Grade 1 cytokine release syndrome (CRS) occurred in 1 patient at DL2, grade 2 CRS in 1 patient at DL3 that was manageable with tocilizumab... In heavily pre-treated patients with advanced myeloid and lymphoid neoplasms, treatment with MDG1011 was generally safe and well tolerated up to 5x106 PRAME-specific TCR-T cells/kg. Clinical observations were corroborated by persistence of MDG1011 cells in PB and reductions in PRAME mRNA levels in PB and/or BM.

We also describe artificial adjuvant vector cells (aAVCs) and BRD9 inhibitors, two additional potential targets for treatment of advanced synovial sarcoma. This review demonstrates the progress that has been made in treatment of synovial sarcoma and highlights the future study and qualification needed to implement these technologies as standard of care.

Conclusion We show that expression of PRAME is common in sinonasal MM, making PRAME a useful ancillary diagnostic tool and a potential therapeutic target in sinonasal MM. The demonstrated occurrence of extensive presence of PRAME-positive melanocytes in the surrounding mucosa of sinonasal MM, might explain the multifocal nature of melanoma in the (sinonasal) mucosa, and would be an extra argument for a PRAME targeting treatment in preventing local disease recurrence.

SOX10 is a more specific and sensitive marker for melanocytes when assessing for LM on excision margins compared with Melan A. The addition of PRAME can be useful to confirm or exclude the diagnosis in challenging cases.

We show that expression of PRAME is common in sinonasal MM, making PRAME a useful ancillary diagnostic tool and a potential therapeutic target in sinonasal MM. The demonstrated occurrence of extensive presence of PRAME-positive melanocytes in the surrounding mucosa of sinonasal MM might explain the multifocal nature of melanoma in the (sinonasal) mucosa, and would be an extra argument for a PRAME targeting treatment in preventing local disease recurrence.

In this limited study, PRAME is expressed in 100% of PEComas demonstrating its utility as an additional IHC marker of melanocytic expression in this difficult tumor type. While PRAME expression was similar to HMB45 in most cases, it was stronger and more diffuse in two cases (33.3%). Additional testing to determine the expression of PRAME in tumors in the differential diagnosis with PEComas is underway.

PRAME is a promising target for the treatment of uterine and pelvic CS The protein expression levels are similar in carcinomatous and sarcomatous components of CS supporting single cell origin There is no PRAME expression difference between high-grade and low-grade carcinomas in this small cohort. Uterine LMS has overall low-PRAME protein expression levels. PRAME protein overexpression seems to be not associated with MLH-1 methylation status.

Although there was almost 100% correlation between PRAME IHC and GEP results, and good correlation with BAP1 IHC expression, the focal immunostaining pattern observed in this cohort of enucleation specimens suggests that PRAME IHC may have utility only for evaluation of large specimens, with limited utility in small fine needle aspiration biopsies.

BAP1 and PRAME appear to play an independent role in progression of UM. In subset of UM patients with tumoral BAP1 expression, PRAME immunoreactivity (H-score >=30) indicates poorer survival. Dual BAP1 and PRAME immunohistochemical evaluation is a promising prognostic panel.

This study indicates the potential of combining (immuno)therapy with HDACi to enhance both T cell-driven and NKcell-driven immune responses in patients with HR-NBL.

PRAME immunohistochemistry also discriminated SAMPUS-FM from SAMPUS-FB with a sensitivity and specificity of 90.0% and 76.5%, respectively. In conclusion, PRAME immunohistochemistry can be used effectively to distinguish between various spectra of acral melanocytic neoplasms.