Glofitamab monotherapy in patients with heavily pretreated relapsed/refractory (R/R) mantle cell lymphoma (MCL): Updated analysis from a phase I/II study.
Authors: Tycel Jovelle Phillips, Carmelo Carlo-Stella, Franck Morschhauser, Emmanuel Bachy, Michael Crump, Marek Trneny, Nancy L. Bartlett, Jan Zaucha, Tomasz Wrobel, Fritz Offner, Audrey Filézac de L’Etang, James Relf, David J. Carlile, Ben Byrne, Estefania Mulvihill, Linda Lundberg, Michael Dickinson
Journal: Journal of Clinical Oncology (2024)

7008 Background: Glofitamab, a bispecific antibody with a novel 2:1 (CD20:CD3) format, engages and redirects T cells to eliminate malignant B cells. In a Phase I/II study (NCT03075696), fixed-duration glofitamab monotherapy showed high, durable complete responses (CR) and manageable safety in patients (pts) with heavily pretreated R/R MCL (Phillips et al. ASH 2022). We report updated efficacy and safety data for pts with R/R MCL. Methods: Pts received obinutuzumab pretreatment (Gpt; 1000mg or 2000mg) 7 days before their first glofitamab dose. Glofitamab step-up dosing was given on Cycle (C) 1 Day (D) 8 (2.5mg) and D15 (10mg), and target dose (16mg or 30mg) from C2D1 to C12 as a fixed-duration therapy. Efficacy endpoints were CR, overall response rate (ORR), duration of CR (DOCR), duration of response (DOR) and progression-free survival (PFS). Post-hoc PFS and overall survival (OS) landmark analyses were performed in pts with a CR at end of treatment (EOT). Results: As of Sept 4, 2023, 61 pts were enrolled; 60 received study treatment (1000mg Gpt, n=16; 2000mg Gpt, n=44). Median number of prior lines of therapy was 2 (range: 1–5); 73.3% were refractory to the last line of prior therapy. Median duration of glofitamab therapy was 7.4 months; median number of cycles was 12. Of the 31 pts (51.7%) who received prior Bruton’s tyrosine kinase inhibitor (BTKi) therapy, 29 (93.5%) were BTKi refractory; median number of prior lines of therapy was 3 (range: 1–5); 90.0% were refractory to the last line of prior therapy. At a median PFS follow-up of 17.2 months, ORR and CR rate were 85.0% and 78.3%, respectively. Median DOCR was 15.4 months; the majority of CRs (28/47; 59.6%) were ongoing at data cut-off. Of 19 pts with a CR, 9 had disease progression and 10 died (fatal adverse event [AE], n=8; COVID, n=7; septic shock, n=1). Estimated 12-month DOCR and DOR rates were 71.0% and 66.6%, respectively. Median PFS was 16.8 months. Landmark analyses indicated that most pts with a CR at EOT were alive and progression free 15 months post-EOT (OS rate, 72.7%; PFS rate, 59.2%). Observed efficacy data were consistent across both Gpt cohorts. In post-BTKi pts after a median PFS follow-up of 26.1 months, ORR and CR rate were 74.2% and 71.0%, respectively. Median DOCR was 12.6 months; median PFS was 8.6 months. No new safety signals were observed. Cytokine release syndrome (CRS) remained the most common AE (42/60, 70.0%; Grade 1/2, 58.3%) and was lower in the 2000mg (63.6%) vs the 1000mg (87.5%) Gpt cohort. Glofitamab monotherapy (2000mg Gpt) is currently under investigation in the Phase III GLOBRYTE study (NCT06084936). Conclusions: Fixed-duration glofitamab continues to demonstrate compelling response rates that are maintained beyond EOT, with long-term durability observed in heavily pretreated pts with R/R MCL, including pts with prior BTKi therapy. The safety profile was manageable and CRS mainly low grade. Clinical trial information: NCT03075696 .