Profile
General Information
Epkinly (epcoritamab-bysp) is a bispecific CD20-directed CD3 T-cell engager.
Epkinly is specifically indicated 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.
Epkinly is supplied as an injection for subcutaneous administration.
Dosing/Administration:
- Administer Epkinly to well-hydrated patients.
- Premedicate before each dose in Cycle 1
- Epkinly should only be administered by a qualified healthcare professional with appropriate medical support to manage severe reactions such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS)
- Administer Epkinly subcutaneously according to the dosage schedule below to reduce the incidence and severity of CRS. Due to the risk of CRS and ICANS, patients should be hospitalized for 24 hours after administration of the Cycle 1 Day 15 dosage of 48 mg.
- See drug label for restarting Epkinly if a dose is delayed and for recommended premedications.
Cycle of treatment (1 cycle = 28 days) | Day of treatment | Dose of Epkinly |
cycle 1 | 1 | Step-up dose 1: 0.16 mg |
cycle 1 | 8 | Step-up dose 2: 0.8 mg |
cycle 1 | 15 | First full dose: 48 mg |
cycle 1 | 22 | 48 mg |
cycles 2 and 3 | 1, 8, 15 and 22 | 48 mg |
cycles 4 to 9 | 1 and 15 | 48 mg |
cycles 10 and beyond | 1 | 48 mg |
Mechanism of Action
Epcoritamab-bysp is a T-cell engaging bispecific antibody that binds to the CD3 receptor
expressed on the surface of T-cells and CD20 expressed on the surface of lymphoma cells and
healthy B-lineage cells.
In vitro, epcoritamab-bysp activated T-cells, caused the release of proinflammatory cytokines,
and induced lysis of B-cells.
Side Effects
Adverse effects associated with the use of Epkinly may include, but are not limited to, the following:
- cytokine release syndrome
- fatigue
- musculoskeletal pain
- injection site reactions
- pyrexia
- abdominal pain
- nausea
- diarrhea
- Grade 3 to 4 laboratory abnormalities (≥ 10%), including decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, decreased hemoglobin, and decreased platelets
The Epkinly drug label comes with the following Black Box Warning: Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving Epkinly . Initiate treatment with the Epkinly step-up dosing schedule to reduce the incidence and severity of CRS. Withhold Epkinly until CRS resolves or permanently discontinue based on severity. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), including life-threatening and fatal reactions, can occur with Epkinly . Monitor patients for neurological signs or symptoms of ICANS during treatment. Withhold Epkinly until ICANS resolves or permanently discontinue based on severity.
Clinical Trial Results
Epkinly was approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
The Phase 1/2 EPCORE NHL-1 trial
In the expansion cohort of the trial, 157 patients with large B-cell lymphoma (LBCL) were enrolled. Among them, 148 patients with DLBCL or high-grade B-cell lymphoma were enrolled, 89 percent of which were diagnosed with DLBCL NOS, including 28 percent with DLBCL transformed from indolent lymphoma, and 14 percent with high-grade B-cell lymphoma (HGBCL). The median number of prior therapies was three, with 29 percent receiving two prior therapies, 32 percent receiving three prior therapies, and 39 percent receiving four or more prior therapies. Eighteen percent had prior autologous hematopoietic stem cell transplantation (HSCT), and 39 percent had prior chimeric antigen receptor (CAR) T-cell therapy. Eighty-two percent of patients had disease refractory to last therapy and 29 percent of patients were refractory to CAR T-cell therapy.
Subcutaneous Epkinly monotherapy demonstrated an overall response (complete or partial response) in 61 percent (90/148 [95 percent confidence interval (CI): 52.5-68.7]) of patients and 38 percent (56/148 [95 percent CI: 30.0-46.2]) achieved complete remission. The median duration of response was 15.6 months (95 percent CI: 9.7-Not reached).