Brand Name
Epkinly
Generic Name
Epcoritamab-Bysp
View Brand Information FDA approval date: May 19, 2023
Classification: Bispecific CD20-directed CD3 T Cell Engager
Form: Injection
What is Epkinly (Epcoritamab-Bysp)?
EPKINLY is a bispecific CD20-directed CD3 T-cell engager indicated for the treatment of: Diffuse Large B-cell Lymphoma and High-grade B-cell Lymphoma adult patients with relapsed or refractory diffuse large B-cell lymphoma , not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after two or more lines of systemic therapy.
Approved To Treat
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Brand Information
EPKINLY (epcoritamab-bysp)
WARNING: CYTOKINE RELEASE SYNDROME AND IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME
Cytokine release syndrome (CRS), including serious or fatal reactions, can occur in patients receiving EPKINLY. Initiate treatment with the EPKINLY step-up dosage 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
1DOSAGE FORMS AND STRENGTHS
EPKINLY is a clear to slightly opalescent, colorless to slightly yellow solution for subcutaneous injection:
- Injection: 4 mg/0.8 mL in a single-dose vial
- Injection: 48 mg/0.8 mL in a single-dose vial
2CONTRAINDICATIONS
None.
3ADVERSE REACTIONS
The following clinically significant adverse reactions are described elsewhere in the labeling:
- Cytokine Release Syndrome
- Immune Effector Cell-Associated Neurotoxicity Syndrome
- Infections
- Cytopenias
3.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Relapsed or Refractory Large B-cell Lymphoma (LBCL)
EPCORE NHL-1
The safety of EPKINLY was evaluated in EPCORE NHL-1, a single-arm study of patients with relapsed or refractory LBCL after two or more lines of systemic therapy, including DLBCL not otherwise specified, DLBCL arising from indolent lymphoma, high grade B-cell lymphoma, and other B-cell lymphomas
- Cycle 1: EPKINLY 0.16 mg on Day 1, 0.8 mg on Day 8, 48 mg on Days 15 and 22
- Cycles 2-3: EPKINLY 48 mg on Days 1, 8, 15, and 22
- Cycles 4-9: EPKINLY 48 mg on Days 1 and 15
- Cycles 10 and beyond: EPKINLY 48 mg on Day 1
Of the 157 patients treated, the median age was 64 years (range: 20 to 83), 60% were male, and 97% had an ECOG performance status of 0 or 1. Race was reported in 133 (85%) patients; of these patients, 61% were White, 19% were Asian, and 0.6% were Native Hawaiian or Other Pacific Islander. There were no Black or African American or Hispanic or Latino patients treated in the clinical trial as reported. The median number of prior therapies was 3 (range: 2 to 11). The study excluded patients with CNS involvement of lymphoma, allogeneic HSCT or solid organ transplant, an ongoing active infection, and any patients with known impaired T-cell immunity.
The median duration of exposure for patients receiving EPKINLY was 5 cycles (range: 1 to 20 cycles).
Serious adverse reactions occurred in 54% of patients who received EPKINLY. Serious adverse reactions in ≥ 2% of patients included CRS, infections (including sepsis, COVID-19, pneumonia, and upper respiratory tract infections), pleural effusion, febrile neutropenia, fever, and ICANS. Fatal adverse reactions occurred in 3.8% of patients who received EPKINLY, including COVID-19 (1.3%), hepatotoxicity (0.6%), ICANS (0.6%), myocardial infarction (0.6%), and pulmonary embolism (0.6%).
Permanent discontinuation of EPKINLY due to an adverse reaction occurred in 3.8% of patients. Adverse reactions which resulted in permanent discontinuation of EPKINLY included COVID-19, CRS, ICANS, pleural effusion, and fatigue.
Dosage interruptions of EPKINLY due to an adverse reaction occurred in 34% of patients who received EPKINLY. Adverse reactions which required dosage interruption in ≥ 3% of patients included CRS, neutropenia, sepsis, and thrombocytopenia.
The most common (≥ 20%) adverse reactions were CRS, fatigue, musculoskeletal pain, injection site reactions, pyrexia, abdominal pain, nausea, and diarrhea. The most common Grade 3 to 4 laboratory abnormalities (≥ 10%) were decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, decreased hemoglobin, and decreased platelets.
Table 11 summarizes the adverse reactions in EPCORE NHL-1.
Clinically relevant adverse reactions in < 10% of patients who received EPKINLY included ICANS, sepsis, pleural effusion, COVID-19, pneumonia (including pneumonia and COVID-19 pneumonia), tumor flare, febrile neutropenia, upper respiratory tract infections, and tumor lysis syndrome.
Table 12 summarizes laboratory abnormalities in EPCORE NHL-1.
Relapsed or Refractory Follicular Lymphoma (FL)
EPCORE FL-1
The safety of EPKINLY in combination with lenalidomide and rituximab was evaluated in EPCORE FL-1, an open-label, randomized, multicenter trial that included patients with relapsed or refractory FL after at least one line of systemic therapy
The recommended EPKINLY dosage schedule was:
- Cycle 1: EPKINLY 0.16 mg on Day 1, 0.8 mg on Day 8, 3 mg on Day 15, and 48 mg on Day 22
- Cycles 2-3: EPKINLY 48 mg on Days 1, 8, 15, and 22
- Cycles 4-12: EPKINLY 48 mg on Day 1
In both treatment arms, lenalidomide was given orally at a dose of 20 mg once daily from Days 1 to 21 for 12 cycles. Rituximab was administered intravenously at a dose of 375 mg/m
Safety results are based on all 243 patients who received EPKINLY, with the exception of data for CRS and ICANS which are based on patients who received EPKINLY at the recommended dosage schedule. The median duration of exposure in this arm was 10 cycles for EPKINLY and 9 cycles for lenalidomide.
Serious adverse reactions occurred in 51% of these patients, including serious infections in 28% of patients and serious CRS in 12% of patients. Fatal adverse reactions within 60 days of last treatment occurred in 0.8% of patients.
Adverse reactions led to permanent discontinuation of EPKINLY in 6% of patients and dose interruption in 75% of patients, with infection as a leading cause. Adverse reactions leading to interruption of EPKINLY in ≥ 5% of patients included respiratory tract infections, CRS, and rash.
In the EPKINLY arm, adverse reactions led to lenalidomide dose interruption in 72%, dose reduction in 22%, and permanent discontinuation in 15%.
The most common (≥ 20%) adverse reactions in the EPKINLY arm were rash, upper respiratory tract infections, fatigue, injection site reactions, constipation, diarrhea, CRS, pneumonia, COVID-19, and fever. The most common Grade 3 to 4 laboratory abnormalities (≥ 10%) were decreases in neutrophil count, lymphocyte count, and platelets.
Table 13 summarizes select adverse reactions in EPCORE FL-1.
Other clinically relevant adverse reactions include:
Gastrointestinal disorders: diarrhea (26%), nausea (16%), abdominal pain (11%), vomiting (4.1%)
Musculoskeletal and connective tissue disorders: musculoskeletal pain (14%), arthralgia (8%)
Nervous system disorders: peripheral neuropathy (12%), dizziness (7%), ICANS (0.8%)
General disorders: edema (12%)
Infections: cytomegalovirus infection (7%), herpesvirus infection (7%), sepsis (2.9%)
Blood and lymphatic system disorders: febrile neutropenia (6%)
Neoplasms: tumor flare (1.2%)
Table 14 summarizes laboratory abnormalities in EPCORE FL-1. Grade 4 laboratory abnormalities in ≥ 2% of the EPKINLY arm included decreases in neutrophils (41%), lymphocytes (13%), and platelets decreased (4.1%).
EPCORE NHL-1
The safety of EPKINLY as monotherapy was evaluated in EPCORE NHL-1, a single-arm study of patients with relapsed or refractory FL after two or more lines of systemic therapy who received EPKINLY following a 2-step up dosage schedule (N=127)
- Cycle 1: EPKINLY 0.16 mg on Day 1, 0.8 mg on Day 8, 3 mg on Day 15, and 48 mg on Day 22
- Cycle 2-3: EPKINLY 48 mg on Days 1, 8, 15, and 22
- Cycles 4-9: EPKINLY 48 mg on Days 1 and 15
- Cycles 10 and beyond: EPKINLY 48 mg on Day 1
With the exception of CRS, the safety results presented below and in Tables 15 and 16 represent data from patients who received the 2-step up dosage schedule. The data presented for CRS reflects the 86 patients who received the recommended 3-step up dosage schedule. The study excluded patients with CNS involvement of lymphoma, allogeneic HSCT or solid organ transplant, ongoing active infection, any patients with known impaired T-cell immunity, creatinine clearance < 45 ml/min, alanine aminotransferase > 3 times the upper limit of normal, and a cardiac ejection fraction < 45%.
Recommended 3-step up Dosage Schedule
Of the 86 patients with relapsed or refractory FL who received EPKINLY following the recommended 3-step up dosage schedule, the median age was 63 years (range: 33 to 90), 57% were male, and 100% had an ECOG performance status of 0 or 1.
The median duration of exposure was 5 cycles (range: 1 to 12 cycles). CRS occurred in 49% of patients, with Grade 1 CRS occurring in 45% and Grade 2 in 9% of patients. Serious adverse reactions due to CRS occurred in 28% of patients who received EPKINLY. Dose interruptions due to CRS occurred in 19% of patients who received EPKINLY.
2-step up Dosage Schedule
Of the 127 patients with relapsed or refractory FL who received EPKINLY following a 2-step up dosage schedule, the median age was 65 years (range: 39 to 84), 62% were male, and 95% had an ECOG performance status of 0 or 1
Serious adverse reactions occurred in 66% of patients who received EPKINLY. Serious adverse reactions in ≥ 5% of patients included CRS, COVID-19, pneumonia, and second primary malignancies.
Fatal adverse reactions occurred in 9% of patients who received EPKINLY, including COVID-19 (5%), pneumonitis (1.6%), cardiac failure (0.8%), pneumonia (0.8%), and sepsis (0.8%).
Permanent discontinuation of EPKINLY due to an adverse reaction occurred in 19% of patients who received EPKINLY. Adverse reactions which resulted in permanent discontinuation of EPKINLY in ≥ 2% of patients included COVID-19, Hepatitis E, pneumonitis, and second primary malignancy.
Dosage interruptions of EPKINLY due to an adverse reaction occurred in 59% of patients who received EPKINLY. Adverse reactions which required dosage interruption in ≥ 5% of patients included COVID-19, CRS, pneumonia, upper respiratory tract infection, and fatigue.
The most common (≥ 20%) adverse reactions were injection site reactions, CRS, COVID-19, fatigue, upper respiratory tract infection, musculoskeletal pain, rash, diarrhea, pyrexia, cough, and headache. The most common Grade 3 to 4 laboratory abnormalities (≥ 10%) were decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and decreased hemoglobin.
Table 15 summarizes the adverse reactions in EPCORE NHL-1.
Clinically relevant adverse reactions in < 10% of patients (N=127) who received EPKINLY included vomiting, pruritus, hepatotoxicity, ICANS, lower respiratory tract infections, cardiac arrhythmias, respiratory tract infections, pneumonitis, second primary malignancy, vision changes, cellulitis, febrile neutropenia, cardiac failure, cytomegalovirus infection and sepsis.
Table 16 summarizes laboratory abnormalities in EPCORE NHL-1.
3.2Postmarketing Experience
The following adverse reaction has been identified during post-approval use of EPKINLY. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Immune system disorders: Hemophagocytic Lymphohistiocytosis (HLH)
4DRUG INTERACTIONS
For certain CYP substrates, minimal changes in the concentration may lead to serious adverse reactions. Monitor for toxicity or drug concentrations of such CYP substrates when co-administered with EPKINLY.
Epcoritamab-bysp causes release of cytokines
5DESCRIPTION
Epcoritamab-bysp is a bispecific CD20-directed CD3 T-cell engager; it is a humanized bispecific IgG1 antibody. Epcoritamab-bysp is manufactured in Chinese hamster ovary (CHO) cells using recombinant DNA technology and has an approximate molecular weight of 149 kDa.
EPKINLY (epcoritamab-bysp) injection for subcutaneous use is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution, free of visible particles.
Each single-dose 4 mg/0.8 mL vial contains epcoritamab-bysp (4 mg), acetic acid (0.19 mg), polysorbate 80 (0.32 mg), sodium acetate (1.7 mg), sorbitol (21.9 mg) and Water for Injection, USP. The pH is 5.5.
Each single-dose 48 mg/0.8 mL vial contains epcoritamab-bysp (48 mg), acetic acid (0.19 mg), polysorbate 80 (0.32 mg), sodium acetate (1.7 mg), sorbitol (21.9 mg) and Water for Injection, USP. The pH is 5.5.
6HOW SUPPLIED/STORAGE AND HANDLING
How Supplied
EPKINLY (epcoritamab-bysp) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution, free of visible particles, supplied in glass vials as follows:
The vial stopper is not made with natural rubber latex.
7PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Cytokine Release Syndrome (CRS)
Inform patients of the risk of CRS, and to immediately contact their healthcare provider should signs and symptoms associated with CRS (e.g., pyrexia, hypotension, hypoxia, chills, tachycardia, headache, and dyspnea) occur at any time. Advise patients with DLBCL or high-grade B-cell lymphoma that they should be hospitalized for 24 hours after administration of the Cycle 1 Day 15 dosage of 48 mg. Advise patients with FL that they may be hospitalized after administration of the Cycle 1 Day 22 dosage of 48 mg. Patients who receive Cycle 1 Day 22 dosage of 48 mg at an outpatient facility should remain in proximity of a healthcare facility that can assess and manage CRS afterwards. Advise all patients who experience symptoms that impair consciousness not to drive and refrain from operating heavy or potentially dangerous machinery until events resolve
Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)
Advise patients of the risk of ICANS, to immediately contact their healthcare provider for signs and symptoms associated with ICANS, which may manifest, for example, as confusional state, lethargy, tremor, dysgraphia, aphasia, and non-convulsive status epilepticus, and that the onset of events may be delayed
Infections
Advise patients of the risk of serious infections, and to contact their healthcare professional for signs or symptoms of serious infection
Cytopenias
Discuss the signs and symptoms associated with cytopenias, including neutropenia and febrile neutropenia, anemia, and thrombocytopenia
Embryo-Fetal Toxicity
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider if they are pregnant or become pregnant
Lactation
Advise women not to breastfeed during treatment with EPKINLY and for 4 months after the last dose
8PRINCIPAL DISPLAY PANEL - 48 mg/0.8 mL Vial Carton
NDC 82705-010-01
epkinly
48 mg/0.8 mL
For subcutaneous injection
Provide enclosed Medication
One single-dose vial.
Genmab
9PRINCIPAL DISPLAY PANEL - 4 mg/0.8 mL Vial Carton
NDC 82705-002-01
epkinly
4 mg/0.8 mL
For subcutaneous injection
Provide enclosed Medication
One single-dose vial.
Genmab
