Glofitamab monotherapy retreatment in patients with heavily pre-treated relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL): Results from a phase I/II study.

7020 Background: Fixed-duration glofitamab, a CD20xCD3 T-cell engaging bispecific antibody with a novel 2:1 configuration, has demonstrated efficacy and manageable safety in a Phase I/II study (NCT03075696) in heavily pre-treated patients (pts) with R/R NHL (Dickinson. N Engl J Med 2022). We report efficacy and safety data for pts with R/R NHL retreated with glofitamab monotherapy after response to initial glofitamab treatment. Methods: Pts who completed initial treatment and achieved complete response (CR), partial response (PR), or stable disease were eligible for retreatment after documented progression. Initial treatment included obinutuzumab pre-treatment (Gpt) 7 days before the first glofitamab dose, then glofitamab intravenously at either a fixed dose of 0.015–25mg (14- or 21-day cycles) or step-up dosing (2.5mg, then 10mg in Cycle C 1, followed by a target dose of 16 or 30mg C2 onward, 21- day cycles) for up to 12 cycles. Retreatment was administered at the escalation dose received or at the highest glofitamab dose cleared in the study at time of retreatment, with Gpt 7 days before the first glofitamab dose. As with initial treatment, retreatment was permitted for 12 cycles or until progression or unacceptable toxicity, whichever occurred first. Results: As of Sept 4, 2023, 13 pts (diffuse large B-cell lymphoma DLBCL, n=4; follicular lymphoma FL, n=4; mantle cell lymphoma MCL, n=2; transformed FL trFL, n=2; high grade B-cell lymphoma, n=1) had received glofitamab retreatment (retreatment dose: 10mg, n=1; 10/16mg, n=1; 2.5/10/30mg, n=11). Median age was 63.0 years (range: 44–81). With initial treatment, 9 pts had CR and 4 pts had PR (best response by investigator). Median time from end of initial treatment to initiation of retreatment was 13.0 months (range: 4.1–27.4). Median number of retreatment cycles received was 5 (range: 2–12). During retreatment, 9 pts (69.2%) responded: CR, 38.5% (FL, n=2; trFL, n=1; MCL, n=2); PR, 30.8% (FL, n=1; trFL, n=1; DLBCL, n=2). Of the 5 pts with CR at retreatment, 3 pts had CR and 2 pts had PR with initial treatment. Of the 4 pts with PR at retreatment, 3 pts had CR and 1 pt had PR with initial treatment. Median retreatment follow-up time was 25.9 months and 5 pts had responses ongoing at data cut-off (FL, n=2; MCL, n=2; trFL, n=1). The safety profile for glofitamab retreatment was consistent with prior reports of glofitamab monotherapy in R/R NHL (Hutchings. J Clin Oncol 2021). Cytokine release syndrome occurred in 7 pts (53.8%; all Grade 1/2). Exploratory data on B-cell pharmacodynamics, CD20 expression, and T-cell status before retreatment will be presented. Conclusions: Glofitamab monotherapy retreatment was efficacious in heavily pre-treated pts with R/R NHL who responded to initial glofitamab treatment before subsequent progression. The safety profile was consistent with that of initial treatment. Clinical trial information: NCT03075696 .