Background: Mogamulizumab is approved to treat relapsed/refractory mycosis fungoides/Sézary syndrome (MF/SS). In the phase 3 MAVORIC study (N=372), mogamulizumab, given 1mg/kg weekly in cycle (C) 1 and then biweekly (Q2W), demonstrated superior efficacy vs vorinostat and a manageable safety profile. Objectives: We present preliminary results (data-cut Nov 2023) from an ongoing phase 2 study of mogamulizumab administered using a 2mg/kg Q4W dosing schedule (NCT04745234) in patients with relapsed/refractory MF/SS after ≥1 systemic therapy. Methods: Primary objective was safety/tolerability. Secondary objectives included: pharmacokinetics/pharmacodynamics, overall response rate (ORR: complete/partial response [CR/PR] lasting ≥4 weeks), compartmental response, and time-to-response (TTR). Descriptive statistics were used. Results: 34 patients were enrolled (median age: 64.0 years; 64.7% male): 17.6% had SS, 82.4% MF (stage IB–IIA: 23.5%; IIB–IIIB: 58.8%; IVA–IVB: 17.6%). Median follow-up was 8.61 months. Treatment-emergent adverse events (AEs) occurred in 97.1% (33/34) of patients; 26.5% had serious AEs. In patients who completed C1 and received ≥1 dose at 2mg/kg (n=32), ORR was 37.5% (12/32; 1 CR): 66.7% (4/6; 1 CR) in SS; 30.8% (8/26) in MF. Compartmental response was 40.6% (13/32; 1 CR) in skin; 20.0% (2/10; 0 CR) in lymph nodes; 100% (9/9; 8 CR) in blood; 0% (0/1) in viscera. Median TTR was 1.82 months (range: 1.0–3.8). Pharmacokinetics/pharmacodynamics results showed increasing mogamulizumab concentrations with repeated doses, reaching steady state by C3 (C3–7, day 1 range: 17,972.8–21,046.0 ng/mL) and depletion of circulating CD7– and CD26– malignant T–cells. Conclusions: Preliminary results showed a promising safety profile and response rates of 2mg/kg Q4W mogamulizumab.
