ORLANDO – A novel bispecific antibody directed against CD20 and CD3 was associated in a phase 1 trial with a high overall response rate among patients with relapsed or refractory B-cell non-Hodgkin lymphomas in early clinical trials, including patients with diffuse large B-cell lymphoma (DLBCL) that had progressed following chimeric antigen receptor (CAR) T-cell therapy.
Neil Osterweill/MDedge News
Dr. Rajat Bannerji
Among 22 patients previously treated for relapsed/refractory follicular lymphoma of grade 1-3a, there were 21 responses (95%), including 17 complete responses (CR) and 4 partial responses (PR), with the remaining patient having stable disease at 12 weeks of follow-up, reported Rajat Bannerji, MD, PhD, from the Rutgers Cancer Institute of New Jersey in New Brunswick.
“We had activity that was fairly robust in this heavily pretreated population with follicular lymphoma, large-cell patients who had not received CAR T and large-cell patients who had received CAR T, mantle cell, and marginal zone [lymphoma],” he said at the annual meeting of the American Society of Hematology.
REGN1979 is an anti-CD20 and anti-CD3 bispecific IgG4 antibody. It is designed to cross-link and activate CD3-expressing T cells on contact with CD20-positive B cells to kill CD20-positive tumor cells independent of T-cell receptor recognition.
The antibody is administered via an escalating dose schedule consisting of initial, intermediate, and step-up doses.
In addition to the follicular lymphoma response rates noted before, patients with heavily pretreated DLBCL who received the antibody at a dose of 80 mg or higher had an overall response rate of 57.9% (11 patients) including 42.1% CR (8 patients), and 15.8% PR (3 patients). Two patients had stable disease at the 12-week assessment, three had disease progression, and three were not available for assessment.
Among seven patients with DLBCL treated at 80 mg or above who had not received CAR T therapy, five had a CR, one had stable disease, and one had disease progression. Of 12 patients with prior CAR T exposure, 3 had complete responses, 3 had partial responses, 1 had stable disease, 2 had progressive disease, and 3 were not available for assessment.
Among six patients with mantle cell lymphoma and six with marginal zone lymphoma treated across all disease levels, the ORR in each cohort was 67%, with two of six patients in each cohort having a complete response, and two having a partial response.
The safety analysis of all 110 patients enrolled showed that no patients experience a dose-limiting toxicity during the escalation phase, and no maximum tolerated doses were identified.
The most common treatment-related adverse events (AEs) were pyrexia in 88 patients, cytokine release syndrome in 65, chills in 56, fatigue in 40, and anemia in 39.
The most common grade 3-4 AEs were anemia in 24, and hypophosphatemia, lymphopenia, and neutropenia in 21 patients each.
Neurologic AEs were transient and did not require treatment discontinuation, and there were no grade 4 neurologic AEs or deaths from neurologic side effects.
Six patients discontinued the study drug because of treatment-related AEs that included cytomegalovirus infection, grade 3 hemolysis, fatigue, pneumonia, and toxoplasmosis.
A total of 15 patients died during the study, 10 of which were caused by progressive disease, with other deaths caused by gastric perforation, cardiac arrest, lung infection, pneumonia, and 1 from fungal pneumonia 7 months after treatment discontinuation. In addition, after the data cutoff, one patient with mantle cell lymphoma blastoid variant with bone-marrow involvement and bulky disease who was enrolled in an expansion cohort died from tumor lysis syndrome.
The dose-escalation portion of the trial has been completed and expansion cohorts are being enrolled. In addition, REGN1979 is being investigated in a phase 2 global multiarm trial.
The study is supported by Regeneron Pharmaceuticals. Dr. Bannerji reported research funding, travel support, and consulting fees from Regeneron and others.
SOURCE: Bannerji R et al. ASH 2019, Abstract 762.