On May 19, 2023, the FDA accelerated the approval of epcoritamab-bysp (Epkinly; Genmab US), a bispecific CD20-directed CD3 T-cell engager, for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma after ≥2 lines of systemic therapy. The FDA granted this application priority review.
The approval was based on response rate and durability of response in the phase 1/2 EPCORE NHL-1 study, an open-label, multicohort, multicenter, single-arm clinical trial of patients with relapsed or refractory B-cell lymphoma. The 148 patients in the efficacy population had relapsed or refractory DLBCL, not otherwise specified, including DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma after ≥2 lines of systemic therapy, including ≥1 anti-CD20 monoclonal antibody–containing therapies.
The main efficacy measure was overall response rate, which was 61% (95% confidence interval [CI], 53-69), with 38% complete responses. Responders had a median follow-up of 9.8 months, with an estimated median duration of response of 15.6 months (95% CI, 9.7-not reached).
The prescribing information for epcoritamab includes a boxed warning for serious or life-threatening cytokine release syndrome (CRS) and life-threatening or fatal immune effector cell–associated neurotoxicity syndrome (ICANS). The warnings and precautions include infections and cytopenias. In 157 patients with relapsed or refractory large B-cell lymphoma who received the recommended dose of epcoritamab, 51% had CRS, 6% had ICANS, and 15% had serious infections. A total of 37% of patients had grade 1 CRS, 17% had grade 2, and 2.5% had grade 3. Grade 1 ICANS occurred in 4.5% of patients, grade 2 in 1.3%, and grade 5 in 0.6%.
The most common (≥20%) adverse reactions were CRS, fatigue, musculoskeletal pain, injection-site reactions, pyrexia, abdominal pain, nausea, and diarrhea. The most common (≥10%) grade 3/4 laboratory abnormalities were decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, decreased hemoglobin, and decreased platelets.
The recommended regimen for epcoritamab is subcutaneous administration in 28-day cycles until disease progression or unacceptable adverse events. The drug’s recommended dose comprises step-up dosing in cycle 1 (0.16 mg on day 1, 0.8 mg on day 8, and 48 mg on days 15 and 22) followed by a fixed dosing of 48 mg weekly during cycles 2 and 3, every other week during cycles 4 through 9, and then every 4 weeks on day 1 of subsequent cycles.
