Clinical trialPhase 3Lymphoma

Glofitamab plus gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx for relapsed or refractory diffuse large B-cell lymphoma (STARGLO): a global phase 3, randomised, open-label trial

The Lancet · 2024274 patients (183 in the Glofit-GemOx group and 91 in the R-GemOx group)

Abramson JS, Ku M, Hertzberg M, Huang HQ, Fox CP, Zhang H, et al. The Lancet. 2024. 404:1940-1954

A newer report of this study has been published: Glofitamab plus gemcitabine and oxaliplatin for relapsed/refractory DLBCL: 3-year follow-up of STARGLO. (2026)

Study type: Clinical trial
Study name: STARGLO
Phase: Phase 3
Design: Randomised, open-label, multicentre trial; 2:1 randomisation with permuted blocks (block size 6) via an interactive voice or web response system, stratified by 1 versus ≥2 prior lines of therapy and relapsed versus refractory status
Sample size: 274 patients (183 in the Glofit-GemOx group and 91 in the R-GemOx group)
Source: The Lancet · 2024
Trial registration: NCT04408638

In plain words

In this study, patients with diffuse large B-cell lymphoma whose disease had come back after earlier treatment or had not responded to it, and who could not have a transplant, received either GemOx chemotherapy with a drug called glofitamab or the same chemotherapy with rituximab. Patients who received glofitamab lived significantly longer. A side effect called cytokine release syndrome occurred in about 44% of patients given glofitamab and was mostly mild to moderate. Decisions about this treatment should be made with your treating doctor, taking each patient's situation into account.

Key results

Glofit-GemOx: not estimable (NE; 95% CI 13.8 months to NE) vs R-GemOx: 9.0 months (7.3 to 14.4)

Median overall survival — primary analysis (median follow-up 11.3 months)

HR 0.59 (95% CI 0.40 to 0.89); P=0.011

25.5 months (18.3 to NE) vs 12.9 months (7.9 to 18.5)

Median overall survival — updated analysis (median follow-up 20.7 months)

HR 0.62 (0.43 to 0.88)

76 (44%) of 172 patients

Cytokine release syndrome (in patients exposed to glofitamab)

Mostly low grade

5 patients (3%) in the Glofit-GemOx group vs 1 patient (1%) in the R-GemOx group

Deaths related to glofitamab or rituximab

Drugs in this study:Gemcitabine (Gemzar)Oxaliplatin (Eloxatin)Rituximab (Rituxan/MabThera)

Dose and schedule cards

Glofitamab + GemOx (STARGLO trial)

Relapsed or refractory DLBCL after one or more lines of therapy in patients who are not transplant candidatesCycle length: Every 21 daysOn the page “Lymphoma” · Treatment regimens and dosing: relapsed or refractory DLBCL, transplant-ineligible and later lines

Relapsed or refractory DLBCL after one or more lines of therapy in patients who are not transplant candidates

Drug	Dose	Route	Schedule
Pretreatment
Obinutuzumab	Single dose	IV	7 days before the first glofitamab dose
Cycles 1–8
Glofitamab	Step-up dosing to 30 mg	IV	Per protocol
Gemcitabine	1000 mg/m²	IV	Each cycle (day per protocol)
Oxaliplatin	100 mg/m²	IV	Each cycle (day per protocol)
Cycles 9–12
Glofitamab	30 mg	IV	Day 1

Cycle length: Every 21 days
Duration: 8 cycles of glofitamab + GemOx followed by 4 cycles of single-agent glofitamab

Doses from the abstract of the STARGLO trial and obinutuzumab pretreatment from the trial registration; the exact days of step-up dosing and GemOx are given in the full text of the article. The obinutuzumab pretreatment dose in the glofitamab label is 1000 mg. Premedication, tumour lysis syndrome prophylaxis and cytokine release syndrome monitoring are the same as for single-agent glofitamab.

On the page “Lymphoma” · Treatment regimens and dosing: relapsed or refractory DLBCL, transplant-ineligible and later lines

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Glofit-GemOx

Pretreatment with a single dose of IV obinutuzumab 7 days before the first glofitamab dose; then IV gemcitabine 1000 mg/m² and oxaliplatin 100 mg/m² with glofitamab step-up dosing to 30 mg, in 21-day cycles; 8 cycles in total, plus 4 additional cycles of glofitamab alone. (183 patients)

2R-GemOx

IV gemcitabine 1000 mg/m² and oxaliplatin 100 mg/m² with rituximab 375 mg/m² on day 1, in 21-day cycles; 8 cycles in total. (91 patients)

Source of the regimen details: Abstract of the paper and ClinicalTrials.gov NCT04408638 (obinutuzumab pretreatment and cycle length)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Transplant-ineligible adult patients (age ≥18 years) with histologically confirmed relapsed or refractory diffuse large B-cell lymphoma after one or more prior therapies. The trial was conducted at 62 centres in 13 countries in Asia and Australia, Europe and North America. Patients were enrolled between 23 February 2021 and 14 March 2023. 158 (58%) were men and 116 (42%) women, and median age was 68 years (interquartile range 58 to 74).

Endpoints

Primary endpoint: overall survival. The independent review committee, which assessed all response-based endpoints, was blinded to treatment group. Efficacy analyses were by intention to treat in all randomised patients. Results are given from the primary analysis (data cut-off: 29 March 2023) and from an updated analysis after all patients had completed study treatment (data cut-off: 16 February 2024). Safety analyses included all patients who received any study treatment.

Safety and side effects

In the safety population, 180 patients (100%) in the Glofit-GemOx group and 84 (96%) of 88 patients in the R-GemOx group had at least one adverse event during the study period. Cytokine release syndrome occurred in 76 (44%) of 172 patients exposed to glofitamab and was mostly low grade. Deaths related to glofitamab or rituximab occurred in 5 patients (3%) in the Glofit-GemOx group and 1 patient (1%) in the R-GemOx group. The rate of grade ≥3 adverse events is not given in the abstract; details in the full text.

Clinical significance and place in guidelines

According to the abstract, Glofit-GemOx significantly improved overall survival compared with R-GemOx in transplant-ineligible patients with relapsed or refractory diffuse large B-cell lymphoma after one or more prior lines of therapy, and the authors support its use in this population. Regulatory approval status and the place of this regimen in clinical guidelines should be checked separately, as the abstract does not mention them.

Limitations

The trial was open-label (although the independent review committee assessing response-based endpoints was blinded to treatment). The primary analysis was at a short median follow-up (11.3 months), and median overall survival in the Glofit-GemOx group could not be estimated at that time. Treatment-related deaths were numerically more frequent in the Glofit-GemOx group (3% versus 1%). The trial was funded by the manufacturer. Other limitations should be checked in the full text.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.