Epcoritamab is a subcutaneously administered bispecific antibody that targets CD3 and CD20 in a 1:1 ratio and activates T cells to destroy CD20-expressing malignant cells. The recent EPCORE NHL-1 clinical trial investigated epcoritamab monotherapy in R/R mature B-cell lymphomas. This agent is administered with a step-up dosing strategy seen consistently across the BsAb drug class. Patients receive a first priming dose of 0.16 mg on cycle 1 day 1, followed by an intermediate dose of 0.8 mg on cycle 1 day 8, followed by the first full dose of 48 mg on cycle 1 day 15. Subsequent doses are administered once weekly for cycles 1-3 followed by every 2 weeks for cycles 4-9, and every 4 weeks starting with cycle 10.
The study enrolled 157 patients globally with median age of 64 and 3 median prior lines of antilymphoma therapy. Nearly 40% of patients had received at least 4 prior lines of therapy, and 83% of patients were refractory to last systemic therapy. Thirty-nine percent of patients had received prior CAR T-cell therapy; 75% of these patients developed progressive disease within 6 months of CAR T-cell therapy.
Among patients treated in the study, the results were as follows:
CR rate 39% with an overall response rate (ORR) of 63%
Duration of response 12 months; duration of objective response not reached in patients with CR
Duration of CR 12 months
Median PFS 4.4 months; median OS not reached
Time to CR of 2.7 months
Toxicity profile was notable for the following:
Any grade CRS in 50%, grade ≥3 in 2.5%
Most CRS occurs with first full dose on cycle 1 day 15 with median time to onset of 20 hours and median time to resolution of 48 hours
Any grade neutropenia in 22%, grade ≥3 in 15%, febrile neutropenia in 2.5%
Any grade anemia in 18%, grade ≥3 in 10%
Injection site reaction, any grade, in 20%
Any grade neurotoxicity in 6%, grade ≥3 in 1 patient (0.6%)
Epcoritamab was granted accelerated approval on May 19, 2023, for use in patients with R/R DLBCL who have received at least 2 prior lines of systemic therapy.
Glofitamab is the more recently approved BsAb for DLBCL. This agent is distinguished by its 2:1 binding configuration that confers bivalency for the CD20 binding site. Glofitamab is delivered intravenously and requires pretreatment with obinutuzumab 1000 mg 7 days before the first dose. With a similar step-up dosing strategy, patients receive a priming dose of 2.5mg on cycle 1 day 8, an intermediate dose of 10mg on cycle 1 day 15, and a first full dose of 30mg on cycle 2 day 1. Subsequent treatments are administered every 21 days for up to 12 cycles.
The open-label phase 1-2 clinical trial of glofitamab monotherapy enrolled 155 patients with a median age of 66 and 3 median prior lines of therapy. Thirty-three percent of patients had received prior CAR T-cell therapy, and 86% were refractory to last line of therapy with 30% refractory to CAR T-cell therapy.