Glofitamab in Relapsed/Refractory B-cell Lymphomas

Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell–Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial

Background and Purpose

Glofitamab is a T-cell engaging by specific antibody that has a 2:1 structure with bivalency for CD20 on B-cells and monovalency for CD3 on T cells. The investigators developed a phase 1 clinical study to evaluate glofitamab in relapsed refractory B-cell non-Hodgkin’s lymphoma.  Patients were pretreated with obinutuzumab to help reduce toxicity.  The data is summarized here.


All patients were given 1,000 mg of obinutuzumab 1 week prior to the first dose of Glofitamab. The first dose of glofitamab was between 0.005 and 30 mg.  A Byesian continuous reassessment method was used to develop the dose escalation steps. The primary endpoint was safety, pharmacokinetics and the maximum tolerated dose.


Following the initial single patient cohorts, 171 patients were treated within conventional multipatient cohorts.  They received at least 1 dose of Glofitamab.  Most patients were heavily pretreated.  Most (155 out of 171 patients) were refractory to prior treatment.  This represented 90% of the patient cohort.  They had received a median of 3 prior therapies.  74.3% of patients, 172, had diffuse large B-cell lymphoma, transformed follicular lymphoma or other aggressive histology. The remaining patients had indolent lymphoma.  5 patients withdrew from treatment because of adverse events.  50.3% of patients, 86/171 because of grade 3 or 4 cytokine release syndrome. This was only seen in 3.5% of patients.

The overall response rate was 53.8%.  36.8% of patients had a complete response.  The higher overall response rate (65.7%.) was the recommended treatment dose used moving forward to the phase 2 portion of the study. Of the 63 patients who had a complete remission, 84.1%, 53 patients, had an ongoing complete response with a maximum of 27.4 months observation.


The authors concluded that in patients with predominantly refractory aggressive B-cell non-Hodgkin’s lymphoma, glofitamab, showed favorable activity with frequent and durable complete responses as well as a predictable and manageable adverse event profile.