Novel Combination Therapy Shows Promising Results in Non-Hodgkin Lymphoma
A recent study has demonstrated that the combination of englumafusp alfa and glofitamab is capable of inducing a response in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) with aggressive histology. The study showed that, out of 83 patients that were in the second-line and beyond setting, the best overall response (BOR) with the combination was 67.0% and the complete response (CR) rate was 57.0%. In patients in the third-line and beyond setting, these rates were 65.7% and 52.8%, respectively.
Background
Glofitamab is an anti-CD20xCD3 T-cell engaging bispecific antibody approved for the treatment of adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified or large B-cell lymphoma arising from follicular lymphoma after at least two lines of systemic therapy. Englumafusp alfa is a costimulatory bispecific antibody-like fusion protein that targets both CD19 on B cells and 4-1BB on immune cells; the agent has previously shown preclinical synergistic activity.
In the open-label, phase 1b BP41072 trial, investigators explored englumafusp alfa in combination with glofitamab in patients with relapsed/refractory B-cell NHL after at least one prior therapy.
Interim Results of the BP41072 Trial
The phase 1b BP41072 trial reported an updated efficacy result at the 2024 EHA Congress for patients with relapsed/refractory aggressive B-NHL (n=83) and safety findings for the overall study population (n=134).
Efficacy Results
- In the second-line setting for patients with large B-cell lymphoma, the combination of englumafusp alfa and glofitamab showed a BOR of 67.0% and a CR rate of 57.0%
- In the third-line setting and beyond, these rates were 65.7% and 52.8%, respectively.
- In patients with aggressive disease who received CAR T-cell therapy previously (n=42), the BOR was 61.9%, and the CR rate was 47.6%.
- In those without prior CAR T-cell therapy in the second-line and beyond setting (n=41), these rates were 73.2% and 66.0%, respectively; in the third-line and beyond setting, the BOR was 71.4%, and the CR rate was 60.7%.
- In patients with aggressive disease who harbor TP53 mutations (n=22), the BOR was 77.0%, and the CR rate was 68.0%.
Safety Results
Regarding safety in the entire population (n=134), any adverse effect (AE) was reported in most patients (97.8%), and any infections in more than half (58.2%); grade 3 and grade 5 infections were in 16.4% and 5.2% of patients, respectively. Additional AEs included cytokine release syndrome (CRS; 55.2%), anemia (32.1%), COVID-19 (26.9%), neutropenia (25.4%), diarrhea (23.9%), and pyrexia (20.9%). Any serious adverse effects (SAEs) occurred in 61.2% of patients, comprising CRS (23.9%), COVID-19 (8.2%), COVID-19–related pneumonia (6.0%), and pyrexia (5.2%).
Any treatment-related AEs (TRAEs) occurred in 89.6% of all patients; 73.1% were related only to glofitamab, 53.0% were related to both agents, and 11.9% were related to englumafusp alfa only. Four patients (3.0%) had any TRAE that led to drug withdrawal, and three patients (2.2%) died due to TRAEs, which included one dose-limiting toxicity of pneumocystis jirovecii pneumonia.
Conclusion
The results of the BP41702 trial have shown the promising antitumor activity with the combination of englumafusp alfa and glofitamab for the treatment of relapsed/refractory non-Hodgkin lymphoma with aggressive histology. Lead study author Franck Morschhauser, MD, PhD, professor of hematology at the University of Lille in France said in a presentation during the meeting that this is the first “off-the-shelf treatment that can replace CAR T[-cell therapy] with the same mechanism of action, and with, we hope, a positive benefit-risk profile.”
Originally Post From https://www.targetedonc.com/view/englumafusp-alfa-glofitamab-combo-delivers-early-responses-in-patients-with-nhl
