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.
This new agent received priority review and is the first FDA-approved T-cell–engaging bispecific antibody for this patient population.
The FDA approval was based on response rate and durability of response in the phase 1/2 EPCORE NHL-1 (NCT03625037) 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).
Epcoritamab’s prescribing information 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%.
Only a qualified healthcare professional should administer epcoritamab, with appropriate medical support to manage severe reactions, including CRS and ICANS. After the cycle-1, day-15 dosage of 48 mg of epcoritamab, patients should be hospitalized for 24 hours because of the risks for CRS and ICANS.
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 or 4 laboratory abnormalities were decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, decreased hemoglobin, and decreased platelets.
“Despite recent advances in treating advanced DLBCL, due to the aggressive nature and complexity of the disease, there remains a need for new options that can provide remission, are tolerable, and can be administered upon relapse. The approval of Epkinly brings a new option—and with it—new hope to patients and the greater lymphoma community,” said Meghan Gutierrez, Chief Executive Officer of the Lymphoma Research Foundation.
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.
This approval may be contingent on confirmatory trials that verify and describe the clinical benefit of epcoritamab. The randomized phase 3 EPCORE DLBCL-1 (NCT04628494) clinical trial is ongoing to confirm the clinical benefit of epcoritamab and to evaluate the drug versus standard-of-care chemoimmunotherapy regimens in patients with relapsed or refractory DLBCL.