Glofitamab is a bispecific antibody with a T – cell-based immunotherapy.
It simultaneously binds to CD20 positive target B cells and CD3 positive T cells.
Glofitamab is a bispecific antibody that recruits T cells to tumor cells.
Glofitamab is distinct in the emerging class of CD20×CD3 bispecific monoclonal antibodies.
It has a novel 2:1 tumor–T-cell binding configuration that confers bivalency for CD20 (B cells) and monovalency for CD3 (T cells), leading to the engagement and redirection of patients’ existing T cells to eliminate malignant B cells.
The prognosis for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is poor.
In the phase 2 part of a phase 1–2 study, we enrolled patients with relapsed or refractory DLBCL who had received at least two lines of therapy previously.
Patients received pretreatment with obinutuzumab to mitigate cytokine release syndrome, followed by fixed-duration glofitamab monotherapy for 12 cycles total.
At a median follow-up of 12.6 months, 39% of the patients had a complete response according to independent review.
Results were consistent among the 52 patients who had previously received chimeric antigen receptor T-cell therapy-35% of whom had a complete response.
The median time to a complete response was 42 days, and the majority (78%) of complete responses were ongoing at 12 months.
The 12-month progression-free survival was 37%.
Discontinuation of glofitamab due to adverse events occurred in 9% of the patients.
The most common adverse event was cytokine release syndrome that occurred in 63% of the patients.
Adverse events of grade 3 or higher occurred in 62% of the patients, with grade 3 or higher cytokine release syndrome in 4% and grade 3 or higher neurologic events in 3%.
It has been approved for relapsed or refractory DLBCL10 after the receipt of at least two lines of therapy include antibody–drug conjugates, tafasitamab with lenalidomide, pixantrone, selinexor, and chimeric antigen receptor (CAR) T-cell therapies.
Although CAR T-cell therapies appear to be the most effective, they are not consistently available.
Not all patients who are selected to receive CAR T-cell infusion actually do so because of disease progression or death while awaiting therapy, and only approximately 40% of patients have durable remission with third-line CAR T-cell therapy.
Obinutuzumab pretreatment is recommended to mitigate cytokine release syndrome.
we enrolled expansion cohorts of patients with DLBCL who had received at least two lines of therapy previously.
Patients 18 years of age or older who had histologically confirmed DLBCL, transformed follicular lymphoma, high-grade B-cell lymphoma, or primary mediastinal large B-cell lymphoma and an Eastern Cooperative Oncology Group performance-status score of 0 or 1.
All the patients had disease that had relapsed after, or was refractory to, at least two previous lines of therapy including at least one anti-CD20 antibody-containing regimen and at least one anthracycline-containing regimen.
Pretreatment with obinutuzumab (1000 mg) is administered intravenously 7 days before the first dose of glofitamab.
Glofitamab was then administered intravenously as step-up doses on day 8 (2.5 mg) and day 15 (10 mg) of cycle 1, followed by a dose of 30 mg on day 1 of cycles 2 through 12 (cycles last 21 days).
In the NP 30179 study there was a 52% overall response rate and the 39% complete response rate: approximately 40% of patients were progression free at 12 months.
The median time to a complete response according to assessment by the independent review committewas 42 days.
The median duration of objective response was 18.4 months, and the
median duration of complete response was not reached.
Complete response was ongoing at 12 months in 78% of the patients with a complete response.
Glofitamab therapy led to a complete response in 39% of the patients with poor-prognosis DLBCL, in which treatment is often ineffective.
Responses were observed early, were durable, with 78% of the patients with a complete response continuing to have remission at 12 months.
The estimated 12-month overall survival of 50% was meaningful given the poor prognosis with conventional chemotherapy in this disease.
Durable complete remissions lasting several years can be observed with this fixed-duration treatment.
The percentage of patients with a complete remission (39%) is similar to reported data regarding the phase 2 dose of epcoritamab and compares favorably with phase 1–2 data regarding odronextamab.
Both these bispecific antibodies are administered until disease progression; however, data from our study indicate that such an approach is not required with glofitamab in order for durable remission to occur.
Grade 3 or higher toxic effects after the receipt of glofitamab occurred in 62% of the patients and were mainly hematologic.
Cytokine release syndrome was the most frequent adverse event,in 63% of the patients, given that it is a common adverse event with T-cell–engaging immunotherapies.
Mitigation strategies: were implemented to reduce the toxicities with obinutuzumab to deplete peripheral B cells and step-up doses of glofitamab enabled the use of an early high target dose of glofitamab (30 mg) while mitigating the severity of cytokine release syndrome.
High-grade cytokine release syndrome was uncommon.
ICANS that were observed with glofitamab therapy were uncommon and mostly mild (grade ≥3 events in 3% of the patients).
In this phase 2 study involving patients with DLBCL, we found that a fixed course of glofitamab therapy induced durable complete responses and is a new active therapy for patients with this disease.
It is a biclonal protein that works by simultaneously binding CD20 positive target B cells and CD3positive T cells, bringing the cells close together and result in a T cell mediated lymphoma killing.
It has a full-length IgG like structure that allows cyclical administration either intravenously or subcutaneously, at intervals 1-4 weeks.
Patients with diffuse large B cell lymphoma (DLBCL) typically exhibit expression of proteins CD20 on the surface of their tumor cells.
Glofitamab gauges T cells to seek out and destroy CD 20 positive lymphphoma Cells in DLBCL.