FDA has approved Epkinly (epcoritamab-bysp) injection for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B‑cell lymphoma after two or more lines of systemic therapy.
Epkinkly is injected subcutaneously (under the skin) in 28-day cycles until disease progression or unacceptable toxicity. The recommended dose is detailed in the prescribing information.
Disease or Condition
Diffuse large B-cell lymphomas are the most common type of non-Hodgkin lymphoma cancer (in which cancer cells form in the lymph system) and are marked by rapidly growing tumors in the lymph nodes, spleen, liver, bone marrow, or other tissues and organs. Signs and symptoms may include swollen lymph nodes, fever, extreme night sweats, fatigue, and weight loss. High-grade B-cell lymphoma is an aggressive form of B-cell lymphoma.
Epkinly was evaluated in EPCORE NHL-1 (NCT03625037), an open-label, multi-cohort, multicenter, single-arm trial in patients with relapsed or refractory B-cell lymphoma. The efficacy population consisted of 148 patients with relapsed or refractory DLBCL, not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after two or more lines of systemic therapy, including at least one anti-CD20 monoclonal antibody-containing therapy.
The main efficacy outcome measure was overall response rate (ORR) determined by Lugano 2014 criteria, as assessed by an Independent Review Committee. The ORR was 61% (95% CI: 53, 69) with 38% of patients achieving complete responses. With a median follow-up of 9.8 months among responders, the estimated median duration of response was 15.6 months (95% CI: 9.7, not reached).
Epkinly is approved under the accelerated approval pathway, under which FDA may approve drugs for serious conditions where there is an unmet medical need and a drug is shown to have an effect on a surrogate or intermediate endpoint that is reasonably likely to predict a clinical benefit to patients. To confirm the clinical benefit of Epkinly, a Phase 3 randomized trial is ongoing, which is evaluating Epkinly compared to standard of care chemoimmunotherapy regimens in patients with relapsed or refractory DLBCL. The primary study outcome is overall survival.
The prescribing information has a Boxed Warning for serious or life-threatening cytokine release syndrome (CRS) and life-threatening or fatal immune effector cell-associated neurotoxicity syndrome (ICANS). Warnings and precautions include infections and cytopenias. Among the 157 patients with relapsed or refractory large B-cell lymphoma who received Epkinly at the recommended dose, CRS occurred in 51% of patients, ICANS in 6%, and serious infections in 15%. Epkinly should only be administered by a qualified health care professional with appropriate medical support to manage severe reactions such as CRS and ICANS. Because of the risk of CRS and ICANS, patients should be hospitalized for 24 hours after the Cycle 1 Day 15 dosage of 48 mg.
The most common adverse reactions were CRS, fatigue, musculoskeletal pain, injection site reactions, fever, abdominal pain, nausea, and diarrhea. The most common grade 3 to 4 laboratory abnormalities were decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, decreased hemoglobin, and decreased platelets. See full prescribing information for additional information on risks associated with Epkinly.
This application received priority review.