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.

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

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.

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.

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.

P2, N=100, Suspended, RAPT Therapeutics, Inc. | Recruiting --> Suspended

P2, N=268, Suspended, RAPT Therapeutics, Inc. | Recruiting --> Suspended

No abstract available

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.

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

The TBX21 subtype was more prevalent than the GATA3 subtype in AITL. The GATA3 subtype was associated with poor prognosis in patients with non-AITL and PTCL-NOS.

The recruitment of CCR4 + Tregs to the postirradiated TME increases the metastatic potential of tumor cells through increased interactions with M2-type TAMs. A significant reduction in post-RT lung metastases in ectopic mouse models was achieved by disrupting the recruitment of both CCR4 + Tregs and CCR2 + myeloid cells, which are TAM precursors.

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

P2, N=100, Recruiting, RAPT Therapeutics, Inc.

P2, N=268, Recruiting, RAPT Therapeutics, Inc.

P2, N=20, Completed, Hanmi Pharmaceutical Company Limited | Recruiting --> Completed | N=90 --> 20 | Trial completion date: Dec 2025 --> Oct 2023 | Trial primary completion date: Nov 2025 --> Oct 2023

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.

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.

P1, N=7, Completed, RAPT Therapeutics, Inc. | Recruiting --> Completed

P1, N=7, Recruiting, RAPT Therapeutics, Inc. | Not yet recruiting --> Recruiting

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.

No abstract available

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

Sponsored by Kyowa Kirin

Hematological responses to mogamulizumab in four refractory lymphocytic HES patients. OCS: oral corticosteroids; pINF-α: pegylated interferon alpha; MEPO: mepolizumab; MOGA: mogamulizumab.

The MAVORIC phase 3 study (NCT01728805) evaluated the efficacy of mogamulizumab compared with vorinostat in patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) – the most common subtypes of cutaneous T-cell lymphoma (CTCL). In participants with advanced MF/SS, HRQL was most impacted by symptoms with the impact varying by patient characteristics rather than disease stage. Assessing patients' individual disease concerns may inform treatment goals and therapeutic choice.

Additionally, the activity of the anti-CC chemokine receptor 4 antibody, mogamulizumab, depends on immune function, including antibody-dependent cytotoxicity. In this comprehensive review, we summarize the immunopathogenesis of HTLV-1 infection in ATL and discuss the clinical findings that should be considered when developing treatment strategies for ATL.

Conclusions FLX475, an oral CCR4 antagonist, has previously demonstrated clear monotherapy and encouraging combination activity with pembrolizumab. 2 3 In this completed Phase 2 cohort of subjects with CPI-naïve NSCLC, FLX475 in combination with pembrolizumab was shown to be well tolerated and has demonstrated encouraging clinical activity compared to pembrolizumab monotherapy in PD-L1+ NSCLC (based on historical results) – in both subjects with low (TPS 1-49%) and those with high (TPS ≥50%) PD-L1 expression – supporting the continued development of this combination therapy for NSCLC.

Not available.

Outcomes: The analysis indicated significant improvement in OS for mogamulizumab treatment compared with UK clinical practice (hazard ratio: 0.36, 95% CI: 0.24, 0.53). Results suggest an OS advantage for patients with advanced MF/SS treated with mogamulizumab in MAVORIC trial compared with UK clinical practice.

A durable clinical response was noted in some patients, and high lymphocyte levels before treatment initiation may be a biomarker for the efficacy of KW-0761. The synergistic effect of KW-0761 for depleting Tregs and other immunotherapies is expected in the future.