A phase I dose-finding study of mogamulizumab in combination with brentuximab vedotin in previously treated mycosis fungoides and Sézary syndrome

Abstract Background: The prognosis for patients (pts) with advanced-stage Mycosis Fungoides (MF) and Sézary syndrome (SS) is poor and more effective and well-tolerated treatments are needed. Mogamulizumab (Moga) is an anti-CCR4 monoclonal antibody that has excellent efficacy in the blood compartment and is approved for pts with MF and SS after one prior systemic therapy. Brentuximab vedotin (BV) is a CD30-targeted antibody drug conjugate that is highly effective in skin and nodal compartments and is approved for pts with CD30-positive MF after one prior therapy. In this investigator-initiated trial (IIT), we explored the combination of BV and Moga in pts with relapsed/refractory (R/R) MF or SS (NCT05414500). Objectives: To determine safety, tolerability and recommended doses of BV and Moga given in combination for pts with R/R MF and SS (primary); to determine the efficacy of this combination (secondary). Study design: This is a single-center, phase 1, 3+3 dose de-escalation study of Moga and BV in R/R MF and SS. Moga is administered on C1D1 at 1 mg/kg weekly x 5 weeks, then every other week for twelve 28-day cycles. BV is administered on C1D2, then on day 1 every 28 days for 12 cycles. The starting dose of BV is 1.8 mg/kg and will be de-escalated to 1.2 mg/kg (level -1) or 1.0 mg/kg (level -2) if needed. The dose limiting toxicity (DLT) evaluation period is 29 days. This IIT is enrolling pts with R/R stage II-IV MF/SS with at least one prior line of systemic therapy with CD30 positivity in >1% tumor cells without prior Moga exposure. Pts with BV exposure more than 6 months prior to study start are allowed. Based on 3+3 design, 9-18 pts are planned. Results and Conclusions: Four pts (all with MF) have been enrolled as of August 5, 2025. Disease stage was IIA (1 pt), IIB (2 pts) and IIIB (1 pt); 3 of 4 pts have large cell transformation. All 4 pts have completed the DLT evaluation period and no protocol-defined DLTs have been observed. Treatment was well-tolerated and all adverse events were grade 1-2 in severity. Adverse events of special interests were infusion reactions (grade 2 in 1 pt, related to Moga), peripheral neuropathy (grade 1 in 1 pt and grade 2 in 1 pt, related to BV) and rash (grade 2 in 2 pts, related to Moga). The most common treatment-related adverse events, all occurring in 2/4 patients, were diarrhea, myalgia, peripheral neuropathy, and rash. Best global responses (Olsen et al. Journal of Clinical Oncology 2011) were partial response (2 pts) and stable disease (1 pt). Two pts completed 12 cycles of therapy whereas 1 pt did not complete all planned cycles due to progression after initial response. Enrollment is ongoing and additional pt data will be presented at the meeting. Acknowledgements: Drug support and trial funding for this study were provided by Pfizer and Kyowa Kirin, Inc.