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DRUG CLASS:

CCR4 receptor antagonist

23d
Clinical significance of NOTCH1 and FBXW7 alterations in adult T-cell leukemia/lymphoma. (PubMed, Int J Hematol)
Thus, mogamulizumab-containing treatment was unable to overcome treatment refractoriness of ATLL with NOTCH1 alterations. Therefore, patients with NOTCH1 alterations are recommended for allogeneic-HSCT.
Journal
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NOTCH1 (Notch 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7)
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Poteligeo (mogamulizumab-kpkc)
29d
New P2 trial
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Poteligeo (mogamulizumab-kpkc)
2ms
Study of Mogamulizumab With DA-EPOCH in Patients With Aggressive T Cell Lymphoma (clinicaltrials.gov)
P2, N=36, Not yet recruiting, Yale University | Trial completion date: Aug 2027 --> Nov 2027 | Trial primary completion date: Aug 2026 --> Nov 2026
Trial completion date • Trial primary completion date
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doxorubicin hydrochloride • cyclophosphamide • etoposide IV • vincristine • prednisone • Poteligeo (mogamulizumab-kpkc)
2ms
Improved survival among elderly patients with aggressive adult T-cell leukemia/lymphoma: Impact of mogamulizumab-containing chemotherapy. (PubMed, Int J Hematol)
Univariate analysis identified comorbidity as a predictor of poor outcomes, but not intensity of MOG-containing treatment, suggesting a different mechanism of action than that of classical chemotherapy. Our study suggests that MOG-containing treatments are an option for elderly patients with ATL.
Journal
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CCR4 (C-C Motif Chemokine Receptor 4)
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Poteligeo (mogamulizumab-kpkc)
3ms
Mogamulizumab and Concomitant Hypofractionated Low-Dose Total Skin Electron Beam Therapy (2 × 4 Gy) in Cutaneous T-Cell Lymphoma: Proof of Principle, Report of Two Cases. (PubMed, Curr Oncol)
We propose that this combination may be a treatment option for patients with SS. Further research is needed to understand the efficacy and tolerability profile of this therapeutic combination and to determine if there is an additive effect of the combination on the response rates when compared with the monotherapy.
Journal
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CCR4 (C-C Motif Chemokine Receptor 4)
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Poteligeo (mogamulizumab-kpkc)
3ms
KEYNOTE-B83: FLX475 Combined with Pembrolizumab in Patients with Advanced or Metastatic Gastric Cancer (clinicaltrials.gov)
P2, N=20, Completed, Hanmi Pharmaceutical Company Limited | Trial completion date: Oct 2023 --> Aug 2024 | Trial primary completion date: Oct 2023 --> Aug 2024
Trial completion date • Trial primary completion date • Metastases
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Keytruda (pembrolizumab) • tivumecirnon (FLX475)
3ms
Small molecule CCR4 antagonists in cutaneous T-cell lymphoma. (PubMed, Cancer Res Commun)
Mogamulizumab, an FDA-approved anti-CCR4 antibody, has shown efficacy in treating MF/SS; however, its side effects have raised concerns, underscoring the need for more effective and less toxic CCR4-targeted therapies...Furthermore, only C021 inhibited tumor growth in CTCL xenograft mice in vivo. These findings suggest that Class I CCR4 antagonists such as C021 exerts more potent anti-tumor effects on CTCL cells in vitro and in vivo compared to Class II CCR4 antagonists like AZD2098, highlighting its potential for clinical application.
Journal • IO biomarker
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CCR4 (C-C Motif Chemokine Receptor 4) • CCL2 (Chemokine (C-C motif) ligand 2) • CCL22 (C-C Motif Chemokine Ligand 22)
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Poteligeo (mogamulizumab-kpkc)
3ms
Systemic treatments with monoclonal antibodies in mycosis fungoides and Sézary syndrome. (PubMed, Dermatol Reports)
In patients with CD30-expressing CTCL, Brentuximab Vedotin has demonstrated better response rates and progression-free survival (PFS); in advanced SS, mogamulizumab has significantly increased PFS. These findings emphasize the need to standardize prognostic factors and improve CTCL treatment.
Review • Journal
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TNFRSF8 (TNF Receptor Superfamily Member 8)
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TNFRSF8 expression
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Adcetris (brentuximab vedotin) • Poteligeo (mogamulizumab-kpkc)
3ms
Mogamulizumab and Brentuximab Vedotin in CTCL and Mycosis Fungoides (clinicaltrials.gov)
P1, N=10, Recruiting, University of Alabama at Birmingham | Trial completion date: Jun 2025 --> Jul 2026 | Trial primary completion date: Dec 2024 --> Apr 2026
Trial completion date • Trial primary completion date • Combination therapy
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TNFRSF8 (TNF Receptor Superfamily Member 8)
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TNFRSF8 positive
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Adcetris (brentuximab vedotin) • Poteligeo (mogamulizumab-kpkc)
4ms
Real World Observational Study of Poteligeo in Adult Patients With MF and SS (PROSPER) (clinicaltrials.gov)
P=N/A, N=73, Active, not recruiting, Kyowa Kirin Pharmaceutical Development Ltd | Recruiting --> Active, not recruiting
Enrollment closed • Real-world evidence • Real-world
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Poteligeo (mogamulizumab-kpkc)
4ms
Atypical Presentation of Invasive Aspergillosis during Treatment with Mogamulizumab. (PubMed, J Fungi (Basel))
Patient started voriconazole but, despite being in a stable condition, he suddenly died after two days. Paradoxically, worsening of the chronic pulmonary aspergillosis has been reported after nivolumab treatment, and immune reconstitution syndromes are usually seen during neutrophil recovery after intensive chemotherapy...We think that the immune restoration associated with Mogamulizumab (also supported by the concurrent clinical response of the skin lesions) could have been detrimental in this case, exacerbating a catastrophic immune response or alternatively masquerading the clinical progression of aspergillosis. Clinicians should be aware of immune reconstitution syndromes possibly leading to fatal outcomes in immunocompromised patients starting CCR-4 antagonists.
Journal
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CRP (C-reactive protein)
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Opdivo (nivolumab) • Poteligeo (mogamulizumab-kpkc)
4ms
Journal • IO biomarker
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CCR4 (C-C Motif Chemokine Receptor 4) • CCL2 (Chemokine (C-C motif) ligand 2) • CCL22 (C-C Motif Chemokine Ligand 22)
5ms
Urticarial mycosis fungoides: A distinctive presentation with blood involvement and a peculiar immunophenotype. (PubMed, J Cutan Pathol)
We present two cases of MF with clinical urticarial lesions and a striking blood involvement that responded to mogamulizumab treatment...Differential diagnoses included urticarial lymphomatoid drug reactions and other lymphomas, like T-cell prolymphocytic leukemia, atypical Sézary syndrome, or adult T-cell lymphocytic leukemia. A low suspicion threshold is necessary for the diagnosis of atypical presentations of MF.
Clinical • Observational data • Retrospective data • Journal
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IL2RA (Interleukin 2 receptor, alpha) • FOXP3 (Forkhead Box P3) • ISG20 (Interferon Stimulated Exonuclease Gene 20)
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Poteligeo (mogamulizumab-kpkc)
5ms
The CCL2-CCR4 axis promotes Regulatory T cell trafficking to canine glioma tissues. (PubMed, J Neurooncol)
Our study validates CCL2-CCR4 as a bi-directional Treg-glioma immunosuppressive and tumor-promoting axis in canine high-grade glioma.
Journal • IO biomarker
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CCR4 (C-C Motif Chemokine Receptor 4) • CD4 (CD4 Molecule) • CCL2 (Chemokine (C-C motif) ligand 2) • FOXP3 (Forkhead Box P3)
5ms
Phase 2 Study to Evaluate RPT193 in Adults With Moderate to Severe T2-high Asthma (clinicaltrials.gov)
P2, N=38, Terminated, RAPT Therapeutics, Inc. | N=100 --> 38 | Trial completion date: Aug 2025 --> Jun 2024 | Suspended --> Terminated | Trial primary completion date: Jun 2025 --> Jun 2024; Study on clinical hold by FDA
Enrollment change • Trial completion date • Trial termination • Trial primary completion date
5ms
Real-life efficacy of immunotherapy for Sézary syndrome: a multicenter observational cohort study. (PubMed, EClinicalMedicine)
Treatment with mogamulizumab was significantly and independently associated with decreased mortality in Sézary syndrome. French Society of Dermatology, Swiss National Science Foundation (IZLIZ3_200253/1) and SKINTEGRITY.CH collaborative research program.
Clinical • Observational data • Journal
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CCR4 (C-C Motif Chemokine Receptor 4)
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Poteligeo (mogamulizumab-kpkc)
5ms
Mogamulizumab and Extracorporeal Photopheresis for the Treatment of Sezary Syndrome or Mycosis Fungoides (clinicaltrials.gov)
P1/2, N=5, Terminated, Emory University | Phase classification: P1b/2 --> P1/2 | N=32 --> 5 | Trial completion date: Apr 2025 --> Oct 2023 | Recruiting --> Terminated | Trial primary completion date: Apr 2025 --> Oct 2023; Lack of funding
Phase classification • Enrollment change • Trial completion date • Trial termination • Trial primary completion date
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Poteligeo (mogamulizumab-kpkc)
5ms
C-X-C motif chemokine ligand 12-C-X-C chemokine receptor type 4 signaling axis in cancer and the development of chemotherapeutic molecules. (PubMed, Tzu Chi Med J)
This review also provides an introduction to protein structures of CXCL12 and CXCR4 and the application of computer simulation and analysis in understanding CXCR4 activation and antagonist binding. Furthermore, examples of strategies and current progress in CXCL12-CXCR4 axis-targeted development of therapeutic anticancer inhibitors are discussed.
Review • Journal
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CXCR4 (Chemokine (C-X-C motif) receptor 4) • CXCL12 (C-X-C Motif Chemokine Ligand 12)
5ms
Immune-related adverse events associated with Mogamulizumab: a comprehensive review of the literature. (PubMed, Expert Rev Anticancer Ther)
Mogamulizumab's ability to augment the host immune response through Treg depletion adds to its efficacy but has wide-ranging implications for autoimmunity across multiple organ systems, similar to immune checkpoint inhibitor therapy. Occurrence of irAEs may be associated with improved overall clinical response, although long-term follow-up studies are needed.
Review • Journal • Adverse events
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CCR4 (C-C Motif Chemokine Receptor 4)
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Poteligeo (mogamulizumab-kpkc)
5ms
Mogamulizumab + Low-Dose Total Skin Electron Beam Tx in Mycosis Fungoides & Sézary Syndrome (clinicaltrials.gov)
P2, N=30, Recruiting, Stanford University | Trial completion date: Aug 2024 --> Dec 2026 | Trial primary completion date: Feb 2024 --> Dec 2026
Trial completion date • Trial primary completion date
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Poteligeo (mogamulizumab-kpkc)
6ms
The CCL2-CCR4 Axis Promotes Regulatory T Cell Trafficking to Canine Glioma Tissues. (PubMed, Res Sq)
CCL2 mRNA was expressed in all glioma cell lines and expression increased when exposed to Tregs but not to CD4 + helper T-cells. Conclusion Our study validates CCL2-CCR4 as a bi-directional Treg-glioma immunosuppressive and tumor-promoting axis in canine high-grade glioma.
Journal • IO biomarker
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CCR4 (C-C Motif Chemokine Receptor 4) • IL2RA (Interleukin 2 receptor, alpha) • CD4 (CD4 Molecule) • CCL2 (Chemokine (C-C motif) ligand 2) • FOXP3 (Forkhead Box P3)
6ms
Enhancing hepatocellular carcinoma management: prognostic value of integrated CCL17, CCR4, CD73, and HHLA2 expression analysis. (PubMed, J Cancer Res Clin Oncol)
This comprehensive evaluation of CCR4, CCL17, and associated markers introduces a nuanced understanding of the HCC immunological milieu, proposing CCR4 + CD73 + stromal cells as critical to HCC pathogenesis and patient stratification.
Retrospective data • Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • CD73 (5'-Nucleotidase Ecto) • CCR4 (C-C Motif Chemokine Receptor 4) • HHLA2 (HERV-H LTR-Associating 2)
6ms
Real World Observational Study of Poteligeo in Adult Patients With MF and SS (PROSPER) (clinicaltrials.gov)
P=N/A, N=80, Recruiting, Kyowa Kirin Pharmaceutical Development Ltd | Trial completion date: Sep 2024 --> Aug 2025 | Trial primary completion date: Sep 2024 --> Aug 2025
Trial completion date • Trial primary completion date • Real-world evidence • Real-world
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Poteligeo (mogamulizumab-kpkc)
6ms
An Efficacy and Safety Study of RPT193 in Adults With Atopic Dermatitis (clinicaltrials.gov)
P2, N=229, Terminated, RAPT Therapeutics, Inc. | Trial completion date: Sep 2024 --> May 2024 | Suspended --> Terminated; Study on clinical hold by FDA
Trial completion date • Trial termination
6ms
Safety and effectiveness of mogamulizumab in relapsed or refractory CC chemokine receptor 4-positive peripheral T-cell lymphoma and relapsed or refractory cutaneous T-cell lymphoma: A post-marketing surveillance in Japan. (PubMed, Hematol Oncol)
The safety and effectiveness of mogamulizumab for PTCL and CTCL in the real world were comparable with the data reported in previous clinical trials. Clinical Trial Registration.
P4 data • Journal
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CCR4 (C-C Motif Chemokine Receptor 4)
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Poteligeo (mogamulizumab-kpkc)
7ms
Testing the Addition of an Anti-cancer Drug, Hu5F9-G4 (Magrolimab), to the Usual Chemotherapy Treatment (Mogamulizumab) in T-Cell (a Type of Immune Cell) Lymphoma That Has Returned After Treatment or Does Not Respond to Treatment (clinicaltrials.gov)
P1/2, N=88, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Jun 2025 | Trial primary completion date: Dec 2025 --> Jun 2025
Trial completion date • Trial primary completion date • Combination therapy • Immune cell
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Poteligeo (mogamulizumab-kpkc) • magrolimab (ONO-7913)
7ms
Flow cytometric profiles with CD7 and CADM1 in CD4+ T cells are promising indicator for prognosis of aggressive ATL. (PubMed, Blood Adv)
Even after mogamulizumab administration, which shows potent effects for peripheral blood lesions, the N fraction was still a useful indicator for prognostic estimation. In summary, this report shows that CADM1 versus CD7 plots in CD4+ T cells are useful indicators of the clinical course and prognosis of aggressive ATL. Therefore, this CADM1 and CD7 profile is suggested to be a useful prognostic indicator consistently from HTLV-1 carriers to aggressive ATL.
Journal
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CD4 (CD4 Molecule) • CD7 (CD7 Molecule)
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Poteligeo (mogamulizumab-kpkc)
7ms
A Narrative Review of the State of the Art of CCR4-Based Therapies in Cutaneous T-Cell Lymphomas: Focus on Mogamulizumab and Future Treatments. (PubMed, Antibodies (Basel))
Continued research aims to optimise treatments, enhance outcomes, and transform CTCL management. This review aims to elucidate the biological rationale and the several agents under various stages of development and clinical evaluation with the actual known data.
Review • Journal • IO biomarker
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CCR4 (C-C Motif Chemokine Receptor 4)
|
Poteligeo (mogamulizumab-kpkc)
7ms
Side effects of dermato-oncologic therapies (PubMed, Dermatologie (Heidelb))
Side effects can manifest themselves in all organ systems. Chronic side effects and long-term harm are possible, especially with ICIs, and require close therapy monitoring and patient education. Knowledge of the side effects and the temporal, sometimes delayed course of their occurrence are essential for diagnosis and prompt initiation of therapy.
Review • Journal • Adverse events
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CCR4 (C-C Motif Chemokine Receptor 4)
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imatinib • Poteligeo (mogamulizumab-kpkc) • Kimmtrak (tebentafusp-tebn)
7ms
Drug-related exanthema under immunotherapy and targeted oncological therapy (PubMed, Dermatologie (Heidelb))
Cutaneous side effects are common across all drug classes and cover a broad spectrum. While some adverse events are specific to one drug class, many exanthemas can occur with both oncological immunotherapies and various targeted therapies. A reliable diagnosis, dose adjustment or discontinuation of the offending agent in consultation with the treating oncologists and appropriate symptomatic therapy are important for correct management. In the case of severe, life-threatening drug reactions, however, permanent discontinuation of the drug is essential.
Review • Journal
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EGFR (Epidermal growth factor receptor) • CCR4 (C-C Motif Chemokine Receptor 4)
|
Poteligeo (mogamulizumab-kpkc)
7ms
Fatal acute graft-versus-host disease in Sézary Syndrome treated with Mogamulizumab and hematopoietic cell transplantation. (PubMed, Curr Res Transl Med)
The patient developed severe gastrointestinal acute GvHD, which was treated with steroids and infliximab. Further research is required to fully understand the interaction between mogamulizumab and allo-HCT and to determine whether it is an optimal approach as a bridge to transplant therapy. This paradigmatic case suggests the need of personalizing transplant strategies by selecting appropriate conditioning therapy and GvHD prophylaxis to minimize potential toxicity.
Journal
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CCR4 (C-C Motif Chemokine Receptor 4)
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Poteligeo (mogamulizumab-kpkc)
9ms
KEYNOTE-877: Dose Escalation and Expansion Study of FLX475 Monotherapy and in Combination With Pembrolizumab (clinicaltrials.gov)
P1/2, N=323, Active, not recruiting, RAPT Therapeutics, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Jan 2025 | Trial primary completion date: Jul 2023 --> Sep 2024
Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy • Metastases
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Keytruda (pembrolizumab) • tivumecirnon (FLX475)
9ms
Allogeneic hematopoietic stem cell transplantation after mogamulizumab in T-cell lymphoma patients: a retrospective analysis. (PubMed, Int J Hematol)
Fourteen patients with known GVHD underwent transplantation between 50 and 365 days after their last dose of mogamulizumab, while 2 underwent transplantation within 50 days after treatment. Based on this limited evidence, GVHD was not associated with the time interval from last mogamulizumab dose to transplantation.
Retrospective data • Journal
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CCR4 (C-C Motif Chemokine Receptor 4)
|
Poteligeo (mogamulizumab-kpkc)
9ms
Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis. (PubMed, Nat Commun)
Furthermore, CNOT3 associates with the protein network largely consisting of ribosomal proteins and translation elongation factors in leukemia cells. Overall, our work elicits the direct requirement for translation efficiency in tumorigenesis and propose targeting the post-transcriptional circuitry via CNOT3 as a therapeutic vulnerability in AML.
Journal • IO biomarker
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CCR4 (C-C Motif Chemokine Receptor 4) • CNOT3 (CCR4-NOT Transcription Complex Subunit 3)
9ms
Unleashed monocytic engagement in Sézary syndrome during the combination of anti-CCR4 antibody with type I interferon. (PubMed, Blood Adv)
Importantly, residual CD4+ T cells following Sézary cell ablation lacked any immunologic shifts. These findings collectively unveil an auxiliary role for augmenting monocytic activity during mogamulizumab therapy in the treatment of SS and underscore the importance of targeted combination therapy in this disease.
Journal
|
CCR4 (C-C Motif Chemokine Receptor 4) • CD4 (CD4 Molecule)
|
Poteligeo (mogamulizumab-kpkc)
9ms
Study of Mogamulizumab With DA-EPOCH in Patients With Aggressive T Cell Lymphoma (clinicaltrials.gov)
P2, N=36, Not yet recruiting, Yale University | Initiation date: Jan 2024 --> Jun 2024
Trial initiation date
|
doxorubicin hydrochloride • cyclophosphamide • etoposide IV • vincristine • prednisone • Poteligeo (mogamulizumab-kpkc)
10ms
Multicenter, randomized, double-blind, placebo-controlled phase 3 study of mogamulizumab with open-label extension study in a minimum number of patients with human T-cell leukemia virus type-1-associated myelopathy. (PubMed, J Neurol)
Although a higher incidence of rash (69.2%) was reported, the safety profile was similar compared with a previous phase 1/2a study. We found no significant difference in clinical benefit; however, mogamulizumab may provide long-term clinical benefit by preventing disease progression, as CSF neopterin/CXCL10 levels are associated with long-term prognosis in HAM/TSP.Clinical Trial Registration Number: NCT03191526 (registered date: 6-June-2017).
Clinical • P3 data • Journal
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CXCL10 (Chemokine (C-X-C motif) ligand 10)
|
Poteligeo (mogamulizumab-kpkc)
10ms
Clinical and Real-World Effectiveness of Mogamulizumab: A Narrative Review. (PubMed, Int J Mol Sci)
While combination with immunostimulatory agents like interferon alpha and interleukin 12 has shown promising results, caution is urged when combining with PD1 inhibitors due to the heightened risk of immune-mediated AEs. The introduction of MOG as a systemic treatment implies a significant advancement in managing these diseases, supported by its favorable safety profile and complementary mechanisms.
Review • Journal • Real-world evidence • Real-world effectiveness • Real-world
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CCR4 (C-C Motif Chemokine Receptor 4)
|
Poteligeo (mogamulizumab-kpkc)
10ms
Phase 2 Study to Evaluate RPT193 in Adults With Moderate to Severe T2-high Asthma (clinicaltrials.gov)
P2, N=100, Suspended, RAPT Therapeutics, Inc. | Recruiting --> Suspended
Trial suspension
10ms
An Efficacy and Safety Study of RPT193 in Adults With Atopic Dermatitis (clinicaltrials.gov)
P2, N=268, Suspended, RAPT Therapeutics, Inc. | Recruiting --> Suspended
Trial suspension
10ms
Journal
|
CCR4 (C-C Motif Chemokine Receptor 4)
|
CCR4 positive
|
Poteligeo (mogamulizumab-kpkc)
10ms
Toxicology, pharmacokinetics, and immunogenicity studies of CCR4-IL2 bispecific immunotoxin in rats and minipigs. (PubMed, Eur J Pharmacol)
Recently, we have compared the in vivo efficacy of CCR4-IL2-IT versus Brentuximab (FDA approved leading drug in CTCL market) in the same immunodeficient mouse CTCL model...The depletion of CCR4+ cell and CD25+ cell (two target cell populations of CCR4-IL2-IT) was observed in minipigs. The excellent safety profile promoted us to further develop CCR4-IL2-IT towards clinical trials.
PK/PD data • Preclinical • Journal
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CCR4 (C-C Motif Chemokine Receptor 4) • IL2RA (Interleukin 2 receptor, alpha) • IL2 (Interleukin 2)
|
Adcetris (brentuximab vedotin)