ABCL-023 frontMIND: A Phase III, Randomized, Double-Blind Study of Tafasitamab + Lenalidomide + R-CHOP Versus R-CHOP Alone for Newly Diagnosed High-Intermediate and High-Risk Diffuse Large B-Cell Lymphoma

Context: The chemo-free immunotherapy tafasitamab + lenalidomide (LEN), has received accelerated approval in the United States (2020) and conditional marketing authorization in Europe and Canada (2021) for treatment of relapsed/refractory diffuse large cell lymphoma (DLBCL), in patients ineligible for autologous stem cell transplant. The primary analysis of First-MIND (NCT04134936) demonstrated that adding tafasitamab + LEN does not impair dosing and scheduling of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), and toxicities were similar to those expected with R-CHOP alone (ASH 2021; #3556). Objective: frontMIND (NCT04824092) will investigate the efficacy and safety of R-CHOP + tafasitamab + LEN versus R-CHOP alone in previously untreated patients with high-intermediate and high-risk DLBCL. Design: A Phase III, multicenter, randomized, double-blind, placebo-controlled study. Setting: Approximately 350 centers from the Americas, Europe, and the Asia-Pacific region. Patients: Eligible patients (n=880) will be aged 18–80 years with previously untreated local biopsy-proven, CD20-positive DLBCL, International Prognostic Index (IPI) score 3–5 (age-adjusted IPI 2–3 if ≤60 years), and ECOG performance score 0–2. Patients with transformed lymphoma are excluded. Interventions: Patients will be randomized 1:1 to receive six 21-day cycles of either R-CHOP + tafasitamab (12 mg/kg intravenously, Days 1, 8, and 15) + LEN (25 mg orally, Days 1–10) or R-CHOP + tafasitamab + LEN placebos. Main Outcome Measures: The primary endpoint is investigator-assessed progression-free survival; secondary endpoints include event-free survival, overall survival, and safety. Minimal residual disease parameters will also be investigated. Results: Results for this study are not yet available. Conclusions: There remains a high unmet need to improve treatment options for newly diagnosed patients with high-intermediate and high-risk DLBCL. The combination of tafasitamab + LEN + R-CHOP may have synergistic potential. Preliminary data from the First-MIND study suggest that tafasitamab ± LEN + R-CHOP may be tolerable in patients with treatment-naïve DLBCL. frontMIND will provide further evaluation of clinical benefits and safety in patients with newly diagnosed high-intermediate and high-risk DLBCL. The study is funded by MorphoSys AG and conducted with the scientific support of members of the Fondazione Italiana Linfomi and the German Lymphoma Alliance.