MCL-339 GLOBRYTE: A Phase III, Open-label Multicenter, Randomized Trial Evaluating Glofitamab Monotherapy in Patients with Relapsed or Refractory Mantle Cell Lymphoma

• Published in: Clinical lymphoma, myeloma and leukemia myeloma and leukemia, 2024-09, Vol.24, p.S515-S515
• Main Authors: Phillips, Tycel, Matasar, Matthew, Eyre, Toby A., Giné, Eva, Filézac de L'Etang, Audrey, Byrne, Ben, Lundberg, Linda, Padovani, Alejandra, Boetsch, Christophe, Bottos, Alessia, Qayum, Naseer
• Format: Article
• Language: English
• Subjects: adverse events; bispecific antibody therapy; clinical trials; mantle cell lymphoma; MCL; non-Hodgkin lymphoma; phase 3
• ISSN: 2152-2650
• DOI: 10.1016/S2152-2650(24)01599-4

Curative treatments are lacking for patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL), particularly for patients progressing on Bruton's tyrosine kinase inhibitors (BTKis). Glofitamab is a CD20xCD3 T-cell-engaging bispecific antibody. Previously, glofitamab monotherapy with step-up dosing (SUD) and obinutuzumab pretreatment (Gpt; 1000/2000mg) showed durable complete response (CR) rates (73.0%) and manageable, predominantly low-grade cytokine release syndrome in heavily pretreated patients with R/R MCL (Phillips et al. ASH 2022). GLOBRYTE (GO43878; NCT06084936) is a phase 3, open-label, multicenter, randomized controlled trial evaluating the efficacy and safety of glofitamab monotherapy in patients with R/R MCL. Inclusion criteria: histologically confirmed R/R MCL; ≥1 prior line of therapy (LOT, including BTKis); and an Eastern Cooperative Oncology Group performance status of 0–2. Exclusion criteria: leukemic, non-nodal MCL; prior chimeric antigen receptor T-cell therapy or CD20xCD3 bispecific antibodies; current/prior primary or secondary central nervous system (CNS) lymphoma; and current/prior CNS disease. Eligible patients will be randomized 1:1 to glofitamab or investigator's choice of rituximab+bendamustine or rituximab+lenalidomide stratified by LOT (1 vs ≥2) and response to last therapy (relapsed vs refractory). Patients will receive intravenous Gpt (2000mg) on Day (D)1 of Cycle (C)1, followed by intravenous glofitamab SUD on C1D8 (2.5mg) and C1D15 (10mg) and the target dose (30mg) on D1 of C2–12. Patients randomized to investigator's choice will receive 375mg/m2 intravenous rituximab on D1 of C1–6 plus either 90mg/m2 intravenous bendamustine (D1–2 of C1–6) or 20mg/day oral lenalidomide (D1–21 until progressive disease). Crossover to glofitamab is permitted at disease progression. All patients must provide informed consent. Primary endpoint: independent review committee (IRC)-assessed progression-free survival (PFS). Secondary endpoints: overall survival; IRC- and investigator-assessed CR rate, objective response rate, duration of response, and duration of CR; investigator-assessed PFS; safety; quality of life; pharmacokinetics; and immunogenicity. Hazard ratios (stratified by LOT and response to last therapy) will be calculated for PFS and overall survival, and odds ratios for the CR rate and overall response rate. Treatment arms will be compared using a 2-sided, 0.05-level stratified log-rank test. Prognostic biomarkers will be exp