Poteligeo (mogamulizumab-kpkc)

Recent years have seen a shift away from chemotherapy with the approval of targeted therapies like mogamulizumab, brentuximab vedotin, and denileukin diftitox-cxdl. Though these novel agents have improved outcomes for patients with advanced-stage CTCL, most patients will continue to experience relapses. Emerging agents, including lacutamab, resminostat, and immune checkpoint inhibitors and biomarkers including CD5, CD70, and CD47/Sirpα represent the next frontier in maintaining durable remissions and improving quality of life (QoL) for these patients.

P2, N=386, Not yet recruiting, Virogen Biotechnology Inc.

In this article, we discuss the clinical and histopathologic findings of cutaneous adverse reactions to newer medications, including those recently approved to treat inflammatory skin diseases, such as dupilumab for atopic dermatitis and IL-12/-23 and IL-23 specific inhibitors for psoriasis, as well as those with oncologic indications, including immune checkpoint inhibitors, mogamulizumab, and enfortumab vedotin.

Tivumecirnon (FLX475) and Zelnecirnon (RPT193), two clinical-stage investigational drugs, bind to the orthosteric site of CCR4, blocking the chemokine recognition site 1. In contrast, AZD2098 and GSK2239633A occupy an allosteric site near the TM7-H8 turn, presumably interfering with G-protein coupling. Further analyses reveal that the therapeutic antibody mogamulizumab binds to the N-terminal region of CCR4 without competing with CCL17, suggesting that its antagonistic effect is mediated exclusively through antibody-dependent cellular cytotoxicity. Together, these structural insights elucidate distinct modes of CCR4 inhibition and provide a framework for the rational design of next-generation therapeutics targeting chemokine receptors.

This is the first documented case of BKPyV-associated PML in a Mogamulizumab-treated patient. These findings highlight intra-host heterogeneity at the protein level, possibly reflecting compartment-specific viral evolution, and underscore the need for vigilant BKPyV and JCPyV monitoring during Mogamulizumab treatment.

The observed median overall survival (OS) was 11.5 months, with 1 reported death due to septic shock in a patient who underwent salvage allo-HSCT after mogamulizumab failure. The results of this study reaffirm the efficacy of Mogamulizumab therapy for patients with Mycosis Fungoides and Sézary Syndrome in a real-world setting, which involves treatment decisions that must often consider patient heterogeneity, comorbidities, and prior lines of therapy.

Therapeutically, agents targeting chemokine pathways, most notably the CCR4 monoclonal antibody Mogamulizumab, have demonstrated clinical efficacy, while emerging inhibitors of CCR6, CCR5, and CXCR4 offer promising avenues for intervention. We further highlight how recent single-cell and other high-dimensional omics studies refine cell-type-specific chemokine sources and receptor expression, enabling more precise mapping of chemokine-driven intercellular communication programs in CTCL TME remodeling and better prioritization of therapeutic targets and biomarkers.

P2, N=23, Recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Dec 2026 --> Apr 2027 | Trial primary completion date: Dec 2025 --> Apr 2026

The patient achieved a partial response with methotrexate but discontinued after ~12 months due to elevated transaminases. Following treatment with bexarotene then gemcitabine, CHOP chemotherapy was initiated in December 2019, but, after a period of partial skin response, the patient relapsed with progression of skin lesions...Disease progression in the skin occurred in December 2020; mogamulizumab was continued, and the patient achieved remission with the addition of etoposide and prednisone in August 2021...In October 2022, the patient was diagnosed with large cell CD30+ transformation, and the therapeutic approach was changed to extracorporeal photopheresis, brentuximab vedotin, and topical steroids. The patient died in February 2023 due to sepsis. Our experience adds to the limited evidence that mogamulizumab may be continued in combination with etoposide following disease progression in patients with MF with blood involvement; however, more research is needed on the efficacy and safety of this approach.

P=N/A, N=100, Completed, Fondazione Italiana Linfomi - ETS | Recruiting --> Completed | N=150 --> 100

XL-11 mediates potent antitumor immunity in advanced HER2+ tumors while avoiding reducing Tregs throughout the body. XL-11 also acts synergistically with anti-PD-1 therapy, and exhibits favorable stability and PK supporting clinical translation. This work advances Treg-targeted therapies in HER2+ tumors and overcomes the therapeutic limitations of mogamulizumab.

P1, N=20, Suspended, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Suspended