PB2112: 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

Background: Tafasitamab is an Fc-enhanced, humanized, anti-CD19 monoclonal antibody which, in combination with the immunomodulatory drug lenalidomide, has been granted accelerated FDA approval and EU conditional marketing authorization based on results from L-MIND (NCT02399085) for the treatment of relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) in adult patients ineligible for autologous stem cell transplant. Treatment schedule optimization aims to reduce the frequency of hospital visits and decrease treatment burden and healthcare utilization while maintaining clinical benefits. Aims: MINDway (NCT05222555) will investigate if administration of tafasitamab at levels higher than the approved 12 mg/kg dose at a reduced dosing frequency can maintain the benefit-risk relationship of tafasitamab + lenalidomide treatment for patients with R/R DLBCL. Methods: MINDway is an open-label, multicenter, Phase Ib/II study in patients aged 18‒80 years with histologically confirmed DLBCL and R/R status after at least one, but no more than three, prior systemic regimens, including CD20-targeted therapy. Patients previously treated with CD19-targeted therapy or with immunomodulatory imide drugs such as lenalidomide are excluded. The modified tafasitamab dosing regimen will be investigated in a stepwise design with two sequential dose-finding cohorts (planned n=6 each) followed by an expansion cohort (planned n=39; Figure). Lenalidomide 25 mg will be administered in all cohorts on Day (D) 1‒21 of each 28-D cycle for up to 12 cycles. After Cycle 12, patients will continue tafasitamab monotherapy at the assigned dosing regimen until progression. Following a review of the safety and pharmacokinetic data from Cohorts 1 and 2, patients will be enrolled in an expansion cohort to receive tafasitamab + lenalidomide at the tafasitamab dose of 24 mg/kg or 30 mg/kg for further evaluation. No intra-patient dose escalation from 24 mg/kg to 30 mg/kg is permitted. The primary endpoint is the incidence and severity of treatment-emergent adverse events; key secondary endpoints include tafasitamab serum concentrations after 3 and 12 treatment cycles and best objective response rate, duration of response, and progression-free survival by investigator assessment. All endpoints will be analyzed using descriptive statistics; no formal statistical tests will be performed. MINDway is currently enrolling, with a planned sample size of 51 patients. Results: Results for this study are not yet available: outcome data as described above will be presented in due course. Image:Summary/Conclusion: MINDway will optimize the tafasitamab dosing regimen to reduce the frequency of hospital/clinic visits for tafasitamab treated R/R DLBCL patients. Reducing the overall frequency of clinic visits by half is expected to reduce the patient burden and support long-term treatment compliance. Furthermore, given the severity of the disease, reduced hospital visits may result in less exposure to hospital infections in this already susceptible population.