KEY TAKEAWAYS
- The STARGLO phase 3 trial aimed to investigate the efficacy and safety of Glofit-GemOx vs R-GemOx in ASCT-ineligible patients with R/R DLBCL.
- The primary endpoint was to determine OS.
- Researchers noticed that Glofit-GemOx significantly improves survival outcomes and maintains a tolerable safety profile.
Glofitamab is a CD20 bispecific antibody that is well tolerated with durable responses when given as fixed-duration monotherapy in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after ≥2 prior lines of therapy (Dickinson, et al. NEJM 2022).
Jeremy Abramson and the team aimed to present efficacy and safety results of Glofit-GemOx versus rituximab (R)-GemOx in patients with R/R DLBCL.
They performed an inclusive analysis in which patients were randomized 2:1 to receive either Glofit-GemOx (8 cycles, plus 4 cycles glofitamab monotherapy) or R-GemOx (8 cycles) and were stratified by the number of prior therapies (1 vs ≥2) and refractoriness to the last treatment. Following obinutuzumab pretreatment, glofitamab was administered during Cycle 1 as weekly step-up doses (2.5/10 mg), then the 30 mg target dose every 21 days from Cycle 2 Day 1.
Patients enrolling after 1 prior therapy were considered ineligible for autologous stem cell transplant (ASCT) based on age ≥70 years, organ dysfunction, ECOG performance status ≥2, patient refusal for ASCT, or other investigator-assessed comorbidities. The primary endpoint was overall survival (OS). Secondary endpoints included independent review committee (IRC)-assessed progression-free survival (PFS), and complete remission (CR) rate. All patients provided informed consent. All study therapy constituted investigational or off-label use.
About 274 patients with DLBCL were enrolled (Glofit-GemOx, n=183; R-GemOx, n=91), including 172 (62.8%) after 1 prior therapy and 102 (37.2%) after ≥2 prior therapies. Overall, 153 (55.8%) had primary refractory disease and 166 (60.6%) were refractory to the last therapy. At primary analysis, there was a significant OS benefit with Glofit-GemOx versus R-GemOx (HR 0.59, 95% CI]: 0.40–0.89; P=0.011). With a median follow-up of 11.3 months, median OS was not reached (95% CI: 13.8–not evaluable) for Glofit-GemOx versus 9 months for R-GemOx (95% CI: 7.3–14.4).
Significant benefit of Glofit-GemOx was also observed in IRC-assessed PFS (HR 0.37, 95% CI: 0.25–0.55; P<0.0001) and CR rate (50.3 vs 22.0%; 95% CI: 16.3–40.3, P<0.0001). A follow-up analysis was conducted once all patients had completed therapy (cut-off date Feb 16, 2024; median follow-up of 20.7 months). Glofit-GemOx continued to demonstrate superior median OS (25.5 vs 12.9 months; HR 0.62, 95% CI: 0.43–0.88), median PFS (13.8 vs 3.6 months; HR 0.40, 95% CI: 0.28–0.57), and CR rate (58.5 vs 25.3%) versus R-GemOx, respectively. Median number of cycles received was higher with Glofit-GemOx versus R-GemOx (11 vs 4).
The adverse event (AE) rates were higher with Glofit-GemOx versus R-GemOx, including Grade (Gr) 3–4 AEs (69.4 vs 36.4%), Gr 5 AEs (8.3 vs 4.5%; primarily driven by an imbalance of COVID-19 AEs), and serious AEs (54.4 vs 17.0%; primarily CRS). Adjusting for exposure differences, AE rates were similar between arms. In patients exposed to glofitamab, CRS was the most frequently reported AE (Gr 1: 31.4%, Gr 2: 10.5%, and Gr 3: 2.3%), and events consistent with immune effector cell-associated neurotoxicity syndrome were reported in 4 patients (2.3%), all of which were concurrent with CRS.
The study concluded that Glofit-GemOx demonstrated statistically significant and clinically meaningful benefits in OS, PFS, and CR rate over R-GemOx in ASCT-ineligible patients with R/R DLBCL. Glofitamab is the first CD20 bispecific antibody to demonstrate a survival benefit in DLBCL in a randomized Phase III trial. Glofit-GemOx, a fixed-duration, off-the-shelf regimen, was well tolerated with a safety profile consistent with the known risks of each individual agent.
The trial was sponsored by the Hoffmann-La Roche.
Clinical Trial: https://clinicaltrials.gov/study/NCT04408638
Abramson J, Ku M, Hertzberg M, et al. (2024). “GLOFITAMAB PLUS GEMCITABINE AND OXALIPLATIN (GLOFIT-GEMOX)FOR RELAPSED/REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA(DLBCL): RESULTS OF A GLOBAL RANDOMIZED PHASE III TRIAL (STARGLO).” Presented at EHA 2024.
