Epcoritamab-bysp

Epcoritamab-bysp
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rithish Nimmagadda,MBBS.[2]

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Black Box Warning

Cytokine Release Syndrome And Immune Effector Cell-associated Neurotoxicity Syndrome See full prescribing information for complete Boxed 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.

Overview

Epcoritamab-bysp is a {{{drugClass}}} that is FDA approved for the treatment of Epcoritamab-bysp is 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.This indication is approved under accelerated approval based on response rate and durability of response.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include The most common (≥20%) adverse reactions are cytokine release syndrome, fatigue, musculoskeletal pain, injection site reactions, pyrexia, abdominal pain, nausea, and diarrhea.The most common Grade 3 to 4 laboratory abnormalities (≥10%) are decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, decreased hemoglobin, and decreased platelets..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Epcoritamab-bysp is available in the following dosage form(s) and strength(s):

Injection: 4 mg/0.8 mL in a single-dose vial. [ref] Dilute prior to use

Injection: 48 mg/0.8 mL in a single-dose vial; supplied as a ready-to-use solution that dose not need dilution prior to administration.

Cycle and Day of Treatment Dose of Epcoritamab-bysp Cycle 1 day 1 (step-up dose 1)- 0.16 mg

Cycle 1 day 8 (step-up dose 2)- 0.8

Cycle 1 day 15 (first full dose)- 48 mg

Cycle 1 day 22- 48 mg

Cycles 2 and 3 days 1, 8, 15, and 22- 48 mg

Cycles 4 to 9 days 1 and 15- 48 mg

Cycle 10 and beyond day 1- 48 mg

Off-Label Use and Dosage (Adult)

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Epcoritamab-bysp FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Contraindications

None

Warnings

Cytokine Release Syndrome And Immune Effector Cell-associated Neurotoxicity Syndrome See full prescribing information for complete Boxed 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.

Cytokine Release Syndrome

Epcoritamab can cause cytokine release syndrome (CRS), including serious or life-threatening reactions.

Cytokine release syndrome occurred in 51% of patients receiving epcoritamab-bysp at the recommended dose in the clinical trial, with Grade 1 CRS occurring in 37%, Grade 2 in 17%, and Grade 3 in 2.5% of patients. Recurrent CRS occurred in 16% of patients. Of all the CRS events, most (92%) occurred during Cycle 1. In Cycle 1, 9% of CRS events occurred after the 0.16 mg dose on Cycle 1 Day 1, 16% after the 0.8 mg dose on Cycle 1 Day 8, 61% after the 48 mg dose on Cycle 1 Day 15, and 6% after the 48 mg dose on Cycle 1 Day 22.

The median time to onset of CRS from the most recent administered epcoritamab-bysp dose across all doses was 24 hours (range: 0 to 10 days). The median time to onset after the first full 48 mg dose was 21 hours (range: 0 to 7 days). CRS resolved in 98% of patients and the median duration of CRS events was 2 days (range: 1 to 27 days).

In patients who experienced CRS, the signs and symptoms included pyrexia, hypotension, hypoxia, dyspnea, chills, and tachycardia. Concurrent neurological adverse reactions associated with CRS occurred in 2.5% of patients and included headache, confusional state, tremors, dizziness, and ataxia.

Initiate therapy according to the step-up dosing schedule. Administer pretreatment medications to reduce the risk of CRS and monitor patients for potential CRS following epcoritamab accordingly. Following administration of the first 48 mg dose, patients should be hospitalized for 24 hours. At the first signs or symptoms of CRS, immediately evaluate patients for hospitalization, manage per current practice guidelines, and administer supportive care as appropriate. Withhold or discontinue epcoritamab based on the severity of CRS.

Patients who experience CRS (or other adverse reactions that impair consciousness) should be evaluated and advised not to drive and to refrain from operating heavy or potentially dangerous machinery until resolution.

Immune Effector Cell-associated Neurotoxicity Syndrome

Epcoritamab can cause life-threatening and fatal immune effector cell-associated neurotoxicity syndrome (ICANS).

ICANS occurred in 6% (10/157) of patients receiving epcoritamab-bysp at the recommended dose in the clinical trial, with Grade 1 ICANS in 4.5% and Grade 2 ICANS in 1.3% of patients. There was one (0.6%) fatal ICANS occurrence. Of the 10 ICANS events, 9 occurred within Cycle 1 of epcoritamab-bysp treatment, with a median time to onset of ICANS of 16.5 days (range: 8 to 141 days) from the start of treatment. Relative to the most recent administration of epcoritamab-bysp, the median time to onset of ICANS was 3 days (range: 1 to 13 days). The median duration of ICANS was 4 days (range: 0 to 8 days) with ICANS resolving in 90% of patients with supportive care. Clinical manifestations of ICANS included, but were not limited to, confusional state, lethargy, tremor, dysgraphia, aphasia, and non-convulsive status epilepticus. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.

Monitor patients for potential ICANS following epcoritamab. [ref] At the first signs or symptoms of ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold or discontinue epcoritamab per recommendations and consider further management per current practice guidelines.

Patients who experience signs or symptoms of ICANS or any other adverse reactions that impair cognition or consciousness should be evaluated, including potential neurology evaluation, and patients at increased risk should be advised not to drive and to refrain from operating heavy or potentially dangerous machinery until resolution.

Infections

Epcoritamab can cause serious and fatal infections.

In the clinical trial, serious infections, including opportunistic infections, were reported in 15% of patients treated with epcoritamab-bysp at the recommended dose with Grade 3 or 4 infections in 14% and fatal infections in 1.3%. The most common Grade 3 or greater infections were sepsis, COVID-19, urinary tract infection, pneumonia, and upper respiratory tract infection.

Monitor patients for signs and symptoms of infection prior to and during treatment with epcoritamab-bysp and treat appropriately. [ref] Avoid administration of epcoritamab in patients with active infections. Provide Pneumocystis jirovecii pneumonia (PJP) prophylaxis prior to initiating treatment with epcoritamab; consider initiating prophylaxis against herpes virus prior to starting the drug.

Withhold or consider permanent discontinuation of epcoritamab based on severity.

Cytopenias

Epcoritamab can cause serious or severe cytopenias, including neutropenia, anemia, and thrombocytopenia.

Among patients who received the recommended dosage of epcoritamab-bysp in the clinical trial, Grade 3 or 4 decreased neutrophils occurred in 32%, decreased hemoglobin in 12%, and decreased platelets in 12% of patients. [ref] Febrile neutropenia occurred in 2.5%.

Monitor complete blood counts throughout treatment. [ref] Based on the severity of cytopenias, temporarily withhold or permanently discontinue epcoritamab. Consider prophylactic granulocyte colony-stimulating factor administration as applicable.

Embryo-fetal Toxicity

Based on its mechanism of action, epcoritamab may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. [ref] Advise females of reproductive potential to use effective contraception during treatment with epcoritamab and for 4 months after the last dose.

Adverse Reactions

Clinical Trials Experience

The most common (≥20%) adverse reactions are cytokine release syndrome, fatigue, musculoskeletal pain, injection site reactions, pyrexia, abdominal pain, nausea, and diarrhea. The most common Grade 3 to 4 laboratory abnormalities (≥10%) are decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, decreased hemoglobin, and decreased platelets

Postmarketing Experience

There is limited information regarding Epcoritamab-bysp Postmarketing Experience in the drug label.

Drug Interactions

It isessential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

For certain cytochrome P-450 (CYP) substrates, minimal changes in the concentration may lead to serious adverse reactions. [ref] Monitor for toxicity or drug concentrations of such CYP substrates when co-administered with epcoritamab-bysp.

Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. Increased exposure of CYP substrates is more likely to occur after the first dose of epcoritamab-bysp on Cycle 1 Day 1 and up to 14 days after the first 48 mg dose on Cycle 1 Day 15, and during and after CRS.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Epcoritamab-bysp in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Epcoritamab-bysp in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Epcoritamab-bysp during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Epcoritamab-bysp in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Epcoritamab-bysp in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Epcoritamab-bysp in geriatric settings.

Gender

There is no FDA guidance on the use of Epcoritamab-bysp with respect to specific gender populations.

Race

There is no FDA guidance on the use of Epcoritamab-bysp with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Epcoritamab-bysp in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Epcoritamab-bysp in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Epcoritamab-bysp in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Epcoritamab-bysp in patients who are immunocompromised.

Administration and Monitoring

Administration

Injection, for subcutaneous use

Monitoring

There is limited information regarding Epcoritamab-bysp Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Epcoritamab-bysp and IV administrations.

Overdosage

There is limited information regarding Epcoritamab-bysp overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Epcoritamab-bysp Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Epcoritamab-bysp Mechanism of Action in the drug label.

Structure

There is limited information regarding Epcoritamab-bysp Structure in the drug label.

Pharmacodynamics

There is limited information regarding Epcoritamab-bysp Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Epcoritamab-bysp Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Epcoritamab-bysp Nonclinical Toxicology in the drug label.

Clinical Studies

The efficacy of EPKINLY was evaluated in EPCORE NHL-1 (Study GCT3013-01; NCT03625037), an open-label, multi-cohort, multicenter, single-arm trial in 157 patients with relapsed or refractory large B-cell lymphoma (LBCL) after two or more lines of systemic therapy. The study excluded patients with CNS involvement of lymphoma, allogeneic HSCT or solid organ transplant, ongoing active infection, and any patients with known impaired T-cell immunity. Patients received EPKINLY monotherapy as a subcutaneous injection according to the following 28-day cycle schedule:

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 Patients continued to receive EPKINLY until disease progression or unacceptable toxicity. In the setting of a suspected tumor flare reaction, continued treatment was permitted.

The efficacy population includes 148 patients with DLBCL, not otherwise specified (NOS), including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma. Of the 148 patients, the median age was 65 years (range: 22 to 83), 62% were male, 97% had an ECOG performance status of 0 or 1, and 3% had an ECOG performance status of 2. Race was reported in 125 (84%) patients; of these patients, 61% were White, 20% were Asian, and 0.7% 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 diagnosis was DLBCL NOS in 86%, including 27% with DLBCL transformed from indolent lymphoma, and high-grade B-cell lymphoma in 14%. The median number of prior therapies was 3 (range: 2 to 11), with 30% receiving 2 prior therapies, 30% receiving 3 prior therapies, and 40% receiving 4 or more prior therapies. Eighteen percent had prior autologous HSCT, and 39% had prior chimeric antigen receptor (CAR) T-cell therapy. Eighty-two percent of patients had disease refractory to last therapy and 29% of patients were refractory to CAR T-cell therapy.

How Supplied

There is limited information regarding Epcoritamab-bysp How Supplied in the drug label.

Storage

There is limited information regarding Epcoritamab-bysp Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Epcoritamab-bysp Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Epcoritamab-bysp interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Epcoritamab-bysp Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Epcoritamab-bysp Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.