Glofitamab plus gemcitabine and oxaliplatin (Glofit-GemOx) in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): 2-year (yr) follow-up of STARGLO.

7015 Background: Glofitamab, a CD20:CD3 bispecific antibody, has shown durable responses as fixed duration monotherapy in R/R DLBCL after ≥2 prior lines of therapy (LOT; Dickinson et al. NEJM 2022). When combined with GemOx, glofitamab has shown overall survival (OS) and progression-free survival (PFS) benefits in autologous stem cell transplant (ASCT)-ineligible R/R DLBCL (Abramson et al. Lancet 2024). We present updated efficacy and safety of Glofit-GemOx vs rituximab (R)-GemOx in pts with R/R DLBCL after ≥1 LOT from the Phase 3 STARGLO trial (NCT04408638), including landmark analyses of pts in complete remission (CR). Methods: Pts were randomized 2:1 to Glofit-GemOx (8 cycles plus 4 cycles glofitamab monotherapy) or R-GemOx (8 cycles) and stratified by no. of prior LOT (1 vs ≥2) and refractoriness to last therapy. After obinutuzumab pretreatment, glofitamab was given in Cycle (C) 1 as weekly step-up doses (2.5/10mg) then 30mg target dose every 21 days from C2 Day 1. Pts with only 1 prior LOT must have been ASCT-ineligible. Primary endpoint was OS. Secondary endpoints included independent review committee (IRC)-assessed PFS and CR rate. A landmark analysis of pts in CR at end of treatment (EOT) was performed. Results: Of 274 pts (Glofit-GemOx, n=183; R-GemOx, n=91), 172 (62.8%) had 1 prior LOT, 102 (37.2%) had ≥2 prior LOT, 153 (55.8%) were primary refractory, and 166 (60.6%) were refractory to last therapy. Baseline characteristics were unchanged and balanced across arms. With 2 yrs follow-up (data cut off: June 17, 2024; median follow-up: 24.7 months [mo]), Glofit-GemOx continued to confer superior OS benefits (median: not evaluable [NE] vs 13.5 mo; HR 0.60, 95% CI: 0.42–0.85), median IRC-assessed PFS (13.8 vs 3.6 mo; HR 0.41, 95% CI: 0.29–0.58), and CR rate (58.5 vs 25.3%) vs R-GemOx. For Glofit-GemOx-treated pts in CR (n=107), median duration of CR was not reached (95% CI: 27.2–NE; median CR follow-up, 18.2 mo [range: 15.2–19.3]). In pts with a CR at EOT (n=82), the OS and PFS rates 1 yr after EOT were 89.3% and 82.4%, respectively. The Glofit-GemOx safety profile was unchanged. Cytokine release syndrome (CRS) was the most common adverse event in glofitamab-exposed pts (Grade [Gr] 1, 32.0%; Gr 2, 10.5%; Gr 3, 2.3%). Events consistent with immune effector cell-associated neurotoxicity syndrome occurred in 4 pts (all concurrent with CRS; most Gr 1–2 [n=3]). Exploratory biomarker and immune recovery data will be presented. Conclusions: With 2 yrs follow-up, Glofit-GemOx sustained a clinically meaningful benefit in OS and PFS vs R-GemOx in ASCT-ineligible pts with R/R DLBCL, with most (82%) pts in CR at EOT still in remission. The safety profile was consistent with known risks of each drug. The updated analyses support the long-lasting remissions and maintained OS benefit in pts with R/R DLBCL treated with fixed duration Glofit-GemOx. Clinical trial information: NCT04408638 .