Poteligeo (mogamulizumab-kpkc)

P2, N=36, Not yet recruiting, Yale University | Trial completion date: Aug 2027 --> Nov 2027 | Trial primary completion date: Aug 2026 --> Nov 2026

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.

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.

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.

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.

P1, N=10, Recruiting, University of Alabama at Birmingham | Trial completion date: Jun 2025 --> Jul 2026 | Trial primary completion date: Dec 2024 --> Apr 2026

P=N/A, N=73, Active, not recruiting, Kyowa Kirin Pharmaceutical Development Ltd | Recruiting --> Active, not recruiting

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.

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.

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.

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

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.

P2, N=30, Recruiting, Stanford University | Trial completion date: Aug 2024 --> Dec 2026 | Trial primary completion date: Feb 2024 --> Dec 2026

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

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.

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

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.

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.

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.

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.

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.

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.

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.

P2, N=36, Not yet recruiting, Yale University | Initiation date: Jan 2024 --> Jun 2024

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).

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.

No abstract available

P2, N=34, Recruiting, City of Hope Medical Center | Trial completion date: Nov 2023 --> May 2025 | Trial primary completion date: Nov 2023 --> May 2025

P=N/A, N=150, Recruiting, Kyowa Kirin, Inc. | N=50 --> 150 | Trial completion date: Feb 2024 --> Feb 2030 | Trial primary completion date: Feb 2024 --> Feb 2030

P1/2, N=88, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting

P1, N=20, Recruiting, H. Lee Moffitt Cancer Center and Research Institute

P2, N=30, Recruiting, Stanford University

P1/2, N=88, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025

P2, N=36, Not yet recruiting, Sethi | Initiation date: Oct 2023 --> Jan 2024

P1/2, N=88, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting | Phase classification: P1b/2 --> P1/2

This is because, although an anti-CCR4 mAb, mogamulizumab, has been approved in Japan to treat ATLL, this therapy failed in a Phase 2 trial among patients outside of Japan. CCL22 but not CCL17 induced strong chemotaxis behavior in NA-ATLL cell lines, which was potently inhibited by a small molecule CCR4 antagonist, CCR4-351. Since extramedullary presentation is frequently seen in NA-ATLL and central nervous system involvement is an adverse prognostic feature, inhibiting chemotaxis with a CCR4 antagonist such as FLX475 may be an effective therapeutic approach.

Our current study showed that the risk of HBVR was 4. 3% (1 of 23) among HBsAg-positive patients with antiviral prophylaxis and 4. 6% (11 of 238) among resolved HBV-infected patients without antiviral prophylaxis following Moga-containing chemotherapy.

Moreover, anti-PD1 (nivolumab), anti-PDL1 (pembrolizumab, atezolizumab), anti-CD52 (alemtuzumab), anti-KIR3DL2-CD158k (lacutamab), and anti-CD70 (cusatuzumab) have been tested or are under investigations in phase II trials. In recent years, targeted (biological) therapies have become available also for primary cutaneous T-cell lymphomas (PCTCLs) including anti-CD30 (brentuximab vedotin) in mycosis fungoides, primary cutaneous anaplastic large T-cell lymphoma, lymphomatoid papulosis; anti-CCR4 (mogamulizumab) in Sezary syndrome; anti-CD123 (tagraxofusp) in blastic plasmocytoid cell neoplasm. The expression of these epitopes on neoplastic cells in skin biopsies or blood samples plays a central role in the management of PCTCL patients. This narrative review aims to provide readers with an update on the latest advances in the newest therapeutic options for PCTCLs.

Among the more successful strategies are the use of consolidative autologous stem cell transplant, the augmentation of CHOP with etoposide (CHOEP), and the use of brentuximab vedotin in CD30-positive PTCL. For patients with acute T-cell leukemia/lymphoma, the use of mogamulizumab-based therapy in the frontline setting may lead to advances in care. The true impact of these new-era therapies will only be elucidated as clinical practices incorporate the rapidly changing evidence.

Treatment is still ongoing for one of them, while the other one relapsed after 10 cycles and was subsequently treated with Alemtuzumab and then with Pembrolizumab. Regarding MF patients, 2 of them are still under treatment, while the other 2 had a disease progression after the 2nd and 3rd cycle, and respectively received RT palliation and Brentuximab...In our small but with a quite long follow-up case series, we confirm the hypothesis that patients with SS may achieve a longer response than MF ones, since mogamulizumab was employed for a mean number of 14 cycles in SS against 4 cycles in MF. In conclusion, mogamulizumab represents a valuable therapy for advanced SS/MF as it can produce prolonged responses in pluryrefractory patients.

P2, N=23, Recruiting, University of Michigan Rogel Cancer Center | Not yet recruiting --> Recruiting

Sponsored by Kyowa Kirin