Merkel Cell Carcinoma

P1/2, N=110, Recruiting, Sotio Biotech Inc. | Trial completion date: Dec 2041 --> Dec 2042 | Trial primary completion date: Apr 2026 --> Oct 2027

P2, N=40, Recruiting, ImmunityBio, Inc. | Active, not recruiting --> Recruiting | N=147 --> 40

P1, N=18, Recruiting, University of Southern California | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2025 --> Jan 2026

P2, N=120, Recruiting, Melanoma and Skin Cancer Trials Limited | Trial completion date: Apr 2028 --> Apr 2030

The epitope of retifanlimab partially overlaps with the ligand binding site, and its binding induced unique conformations of the flexible loops within PD-1, including BC, C'D, and FG loops, thereby optimizing interactions with the antibody. A thorough analysis of its interaction with PD-1 and other FDA-approved anti-PD-1 antibodies may provide valuable insights into the rational design of enhanced therapies to regulate immune responses in cancer treatment.

In addition, analysis of the effect of Sm t-Ag on the growth promoting pathways including those active in the PI3K/Akt/mTOR axis showed substantially higher levels of the phosphorylated-Akt, -Gsk3-β and -S6K1 in Sm t-Ag-positive cells. Collectively, our results demonstrate that Sm t-Ag promotes cell cycle progression by activating the growth promoting pathways through which it may contribute to LT-Ag-mediated cell transformation.

Overall, LAG-3 is expressed in MCC infiltrates and is prognostic in pre-immunotherapy MCC, suggesting a potential role for LAG-3 inhibition in MCC. Additionally, CD8 and γδ-T cells may play a critical role in the response to MCC, and γδ-T cell density may represent a novel biomarker in MCC.

P1/2, N=19, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=12 --> 19

P2, N=77, Terminated, Regeneron Pharmaceuticals | Active, not recruiting --> Terminated; Sponsor Decision related to study drug supply

P2, N=26, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting

P1, N=182, Active, not recruiting, Incyte Corporation | Trial completion date: Oct 2025 --> Dec 2024 | Trial primary completion date: Jul 2025 --> Aug 2024

P1/2, N=7, Terminated, Fred Hutchinson Cancer Center | Trial completion date: Jan 2025 --> Jan 2024 | Active, not recruiting --> Terminated; Terminated due to insufficient funding

However, the combined use of β-catenin with CDX2 markers may assist in not only confirming the pilomatrical nature of the proliferation but also in differentiating benign from malignant cases when there is a significant presence of CDX2 staining. Despite these findings, the diagnosis should continue to primarily depend on a thorough histopathologic examination.

Our results offer crucial reference value for clinical diagnostic assistance.

Three months later, imaging suggested a liver mass consistent with liver cancer. Lab tests showed elevated hepatitis B surface antigen (>130 IU/ml) and alpha-fetoprotein (24.54 IU/ml), and the imaging features resembled hepatocellular carcinoma (HCC).Finally,it was diagnosed as liver metastasis of Merkel cell carcinoma by pathology.

P=N/A, N=20, Recruiting, University of Wisconsin, Madison | Not yet recruiting --> Recruiting

A rearrangement in the tumor suppressor gene SUFU was identified, a likely driver and potential target of the Hedgehog signaling pathway. Meanwhile, the second case exhibited a less aggressive behavior, harbored UV-signature mutations, and a high mutational burden including mutations in TP53 and RB1.

P1, N=12, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Sep 2025

P2, N=9, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Sep 2025

P1, N=105, Terminated, Incyte Corporation | Trial completion date: Jun 2026 --> Aug 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2026 --> Aug 2024; A business decision was made to discontinue further enrollment. There were no safety concerns that contributed to this decision.

This study is the first to report and characterize NETs in NMSC. Thus, it gives an incentive for further research in this relevant yet understudied topic.

P2, N=107, Completed, Incyte Corporation | Active, not recruiting --> Completed

Our results suggest that STING agonists may be able to work indirectly in MCC via signaling through immune and stromal cells in the TME, and may not necessarily need STING expression in the cancer cells. This approach may be particularly effective in tumors that are already infiltrated by inflammatory cells in the TME but are evading immune detection via HLA-I downregulation.

The findings underscore the need for comprehensive diagnostic evaluation when encountering complex or atypical skin lesions. This report emphasizes the rarity of subcutaneous MCC coexisting with BD and underscores the importance of comprehensive diagnostic assessment in unusual cases. Further research is warranted to better understand the underlying mechanisms and to guide optimal management strategies for such rare and challenging presentations.

PD1-L expression, MCC polyomavirus (MCPyV) positivity, and an impaired neutrophil-to-lypmhocyte ratio (NLR) could not be associated with responses to the therapy. Avelumab is an effective and safe drug for the management of advanced MCC, and its effectiveness appears to be impacted by the number and location of metastases.

Using single cell sequencing approaches and computational analyses of MCC and CLL from a patient where both cancers were present in the same lymph node, we found that production of macrophage migration inhibitory factor (MIF) by MCC could promote the persistence of CLL through stimulation of CD74 and CXCR4. These results may explain why blood cell counts rapidly normalized after treatment for MCC and were maintained at normal levels despite the absence of treatment for CLL.

POU4F3 immunostain was performed on 29 sentinel lymph nodes and strong POU4F3 nuclear expression facilitated ease of metastasis detection, even single tumor cells. Our study built on prior works shows that POU4F3 to be a sensitive and specific clinical marker of MCC.

This study demonstrates that neuroendocrine neoplasms, such as MCC and SCLC can express strong aberrant BCOR. This might represent a diagnostic challenge or pitfall, in particular when MCC is clinically mistaken as a soft tissue or a bone sarcoma.

P=N/A, N=20, Not yet recruiting, University of Wisconsin, Madison

P1, N=23, Completed, TuHURA Biosciences, Inc. | Active, not recruiting --> Completed

P1, N=60, Recruiting, KaliVir Immunotherapeutics | Not yet recruiting --> Recruiting

P1, N=200, Active, not recruiting, SOTIO Biotech AG | Trial primary completion date: Aug 2024 --> Dec 2024

P=N/A, N=54, Terminated, Washington University School of Medicine | N=125 --> 54 | Recruiting --> Terminated; Subject recruitment was limited severely by the 2020-2023 COVID-19 pandemic, which led this study to be closed.

Differential diagnoses of BPDCN include myeloid sarcoma, myelomonocytic leukemia, mature plasmacytoid dendritic cell proliferation (MPDCP) and Merkel cell carcinoma. Pathologists ought to be familiar with this WHO entity for early disease diagnosis, because of disease rarity and diagnosis difficulties.

P1, N=22, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting | N=32 --> 22

Our case provides further evidence supporting the hypothesis of a significant association between immunosuppression and MCC pathogenesis.

We provide detailed protocols for investigators to incorporate these mIF panels into their investigations of human and murine MCC. We also provide fundamental guidance for mIF assay development that will be broadly useful for investigators who are considering modifying the panels presented here, or developing their own mIF panels.

P2, N=26, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Feb 2025 --> May 2026

P1/2, N=16, Recruiting, National Cancer Institute (NCI) | Phase classification: P2 --> P1/2

Current guidelines recommend surveillance for up to 3 years post-treatment, but factors, such as patient demographics and tumor characteristics, may warrant extended monitoring periods. Emerging biomarkers, such as Merkel cell polyomavirus status and circulating tumor DNA, show promise in predicting and monitoring recurrences, but their utility in late recurrence detection requires further investigation.

P2, N=147, Active, not recruiting, ImmunityBio, Inc. | Phase classification: P2b --> P2 | Trial completion date: Dec 2024 --> Dec 2030 | Trial primary completion date: May 2024 --> Aug 2029

Furthermore, polyomavirus ALTOs downregulate their respective viral early transcription in an NF-κB- and NTAR-dependent manner. Our findings suggest that ALTOs evolved to suppress viral replication and promote viral latency and that MCPyV ALTO must be silenced for MCC to develop.