ABCL-052 MINDway: A Phase Ib/II Dose Optimization Study to Assess Safety and Pharmacokinetics of Tafasitamab + Lenalidomide in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Abstract

The chemo-free immunotherapy tafasitamab + lenalidomide has been granted FDA accelerated approval and EU conditional marketing authorization for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) treatment in autologous stem cell transplant-ineligible adults. Treatment schedule optimization aims to reduce the frequency of hospital visits and decrease treatment burden and healthcare utilization. MINDway (NCT05222555) will investigate if tafasitamab administration at levels higher than the approved 12 mg/kg dose at a reduced dosing frequency maintains the benefit-risk relationship of tafasitamab + lenalidomide for patients with R/R DLBCL. To assess an optimized tafasitamab treatment schedule in patients with R/R DLBCL. Open-label, multicenter, Phase Ib/II study. Currently enrolling; the planned sample size is 51 patients. Eligible patients are aged 18-80 years with histologically confirmed R/R DLBCL and 1-3 prior systemic regimens, including CD20-targeted therapy. Patients previously treated with CD19-targeted therapy or immunomodulatory imide drugs, such as lenalidomide, are excluded. The modified dosing regimen will be investigated in a stepwise design: two sequential dose-finding cohorts (planned n=6 each) followed by an expansion cohort (planned n=39). Lenalidomide 25 mg will be administered in all cohorts on Days 1-21 of each 28-day cycle for up to 12 cycles. After Cycle 12, patients will continue tafasitamab monotherapy at the assigned dosing regimen until progression. After reviewing safety and pharmacokinetic data from Cohorts 1 and 2, patients will be enrolled in an expansion cohort to receive tafasitamab + lenalidomide (tafasitamab dose: 24 or 30 mg/kg) for further evaluation. No intra-patient dose escalation from 24 to 30 mg/kg is permitted. The primary endpoints are the incidence and severity of treatment-emergent adverse events. Key secondary endpoints are tafasitamab serum concentration after 3 and 12 cycles, best objective response rate, duration of response, and progression-free survival. Not yet available. MINDway will evaluate an optimized tafasitamab dosing regimen to reduce the frequency of hospital/clinic visits for tafasitamab-treated patients with R/R DLBCL. Reducing the frequency of visits by half is expected to reduce patient burden and support long-term treatment compliance. Fewer visits may result in less exposure to hospital infections in this already susceptible population. MorphoSys AG.