Epcoritamab

Epcoritamab (Epkinly) is used to treat relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) in adults. It is given as an injection under the skin (subcutaneously) every 1 to 4 weeks.

Epcoritamab is a bispecific CD20-directed CD3 T-cell engager approved to treat adults with relapsed or refractory (R/R):

• 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. Approved under accelerated approval; continued approval may depend on confirmatory trial results demonstrating clinical benefit.
• Follicular lymphoma (FL), in combination with lenalidomide and rituximab.
• FL after two or more lines of systemic therapy, as monotherapy.

Clinical Trial Results

Epcoritamab (Epkinly) first gained FDA approval on May 19, 2023, under the accelerated approval designation. Full approval was granted for R/R FL on November 18, 2025, based on the results of the Phase 3 EPCORE FL-1 clinical trial (NCT05409066), which demonstrated:

• Epcoritamab, in combination with rituximab and lenalidomide (epcoritamab + R2), reduced the risk of disease progression or death by 79% compared to rituximab and lenalidomide alone (hazard ratio 0.21, 95% CI: 0.13-0.33, p<0.0001).
• For the overall response rate, 89% of patients receiving epcoritamab with rituximab and lenalidomide responded to treatment (216 out of 243 patients, 95% CI: 84-93%; p<0.0001), versus 74% response rate with rituximab and lenalidomide alone (181 out of 245 patients, 95% CI: 68-79%).

Previous results from the EPCORE NHL-1 (NCT03625037) clinical trial reported:

• 61% of patients with R/R DLBCL responded to treatment (overall response rate) and responses lasted a median of 15.6 months.
• 82% of patients with R/R FL responded to treatment, and >50% were still responding at 14.8 months.

Epcoritamab (Epkinly) has a bispecific mechanism of action and works by binding to two different immune system targets: the CD20 protein on B cells and the CD3 protein on T cells. This brings T cells into proximity to B cells, making them more effective at killing cancerous B cells.

Epcoritamab belongs to the drug class called Bispecific T-cell engagers (BiTE). This is a newer category of immunotherapy that harnesses the body's immune system to target cancer more effectively by connecting cancer-fighting T cells directly to the cancerous B cells they need to eliminate.

Epcoritamab will be given as an injection under your skin (subcutaneous injection) by your healthcare provider.

• It is usually given in the lower part of your stomach area (abdomen) or the upper, outer, thigh.
• Your treatment schedule is divided into cycles that are usually 28 days (4 weeks) long.
• Epcoritamab is usually given 1 time a week during Cycles 1 to 4, every 2 weeks from Cycle 4 to 9, and every 4 weeks starting with Cycle 10.
• Your healthcare provider will decide how many treatment cycles you will receive.

Your healthcare provider may hospitalize you for 24 hours after administration of the Cycle 1 Day 15 dosage of 48 mg.

Before administering epcoritamab, you may receive premedications to decrease the risk of CRS.

• These premedications may include a steroid such as prednisolone or dexamethasone or equivalent, an antihistamine such as diphenhydramine or equivalent, and acetaminophen.
• Premedications for the remaining cycles include prednisolone or dexamethasone or equivalent.

Before you receive treatment, tell your healthcare provider about all of your medical conditions, including if you:

• have an infection
• are pregnant or intend to become pregnant
• are breastfeeding.

Pregnancy

This medicine may cause harm to your unborn baby. Females who can become pregnant:

• Your healthcare provider should do a pregnancy test before you start treatment
• You should use effective birth control (contraception) during treatment, and for 4 months after your last dose
• Tell your healthcare provider if you become pregnant or think that you may be pregnant during treatment.

Breastfeeding

Do not breastfeed during treatment and for 4 months after your last dose of epcoritamab.

The most common side effects of epcoritamab are:

• Diarrhea
• Fever
• Injection site reactions
• Muscle and bone pain
• Nausea
• Stomach-area (abdominal) pain
• Tiredness.

Serious side effects and warnings

Epcoritamab carries a Boxed Warning for cytokine release syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).

Cytokine Release Syndrome (CRS)

This immune system overreaction is common during treatment and can become serious or life-threatening. Seek immediate medical attention if you experience:

• Temperature of 100.4°F (38°C) or higher
• Dizziness or lightheadedness
• Breathing difficulties
• Chills or shaking (tremors)
• Accelerated heartbeat
• Feelings of anxiety
• Headache or confusion
• Balance or movement difficulties, including walking problems.

Special Dosing Approach for Safety:

• Treatment follows a gradual "step-up dosing schedule"
• You'll receive smaller initial doses on Day 1 and Day 8 of Cycle 1
• Your first full dose comes on Day 15 of Cycle 1
• Delayed doses may require repeating the step-up schedule
• Preventive medications will be given before doses in Cycle 1
• Your healthcare team will determine if preventive medications are needed in future cycles.

Neurologic Problems (ICANS)

Serious neurological issues may develop days or weeks after treatment, potentially becoming life-threatening. Alert your healthcare provider immediately if you notice:

• Speech or writing difficulties
• Disorientation or confusion
• Drowsiness or unusual fatigue
• Muscle weakness
• Tremors or seizures
• Memory issues.

Hospital Monitoring

Because of the risk of CRS and ICANS:

• 24-hour hospitalization follows your first full dose on Day 15 of Cycle 1
• Your healthcare team will monitor for CRS, neurologic problems, and other side effects
• Treatment may be temporarily or permanently discontinued if serious side effects occur.

Infections

Potentially fatal infections can occur. Report these symptoms immediately:

• Fever of 100.4°F (38°C) or higher
• Coughing or chest pain
• Unusual tiredness
• Breathing difficulties
• Painful rash
• Sore throat
• Painful urination
• General weakness or feeling unwell.

Low Blood Cell Counts

Regular blood tests will monitor for:

• Low white blood cells (neutropenia), increasing infection risk
• Low red blood cells (anemia), causing fatigue and shortness of breath
• Low platelets (thrombocytopenia), leading to bruising or bleeding problems.

Additional Information

• Safety and effectiveness in children has not been established
• This list doesn't include all possible side effects
• Report side effects to FDA at 1-800-FDA-1088
• Contact your doctor for medical advice about side effects.

Adult Dose for Diffuse Large B-cell Lymphoma (DLBCL) or High-grade B-cell Lymphoma

The dose of epcoritamab for DLBCL or high-grade B-cell lymphoma depends on the Cycle and day of treatment. Your healthcare provider will calculate the dosage.

Adult Dose for Follicular Lymphoma (FL)

The dose of epcoritamab for FL depends on the Cycle and day of treatment. Your healthcare provider will calculate the dosage.

Epcoritamab may cause dizziness, confusion, tremors, sleepiness, or other symptoms that may impair your ability to drive or operate heavy machinery, and you should not do these tasks if you are impaired.

• These may be symptoms of CRS or neurologic problems and you should tell your healthcare provider right away.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Epcoritamab may cause small changes in the concentration of other medications that are metabolized by the CYP hepatic enzyme system. Monitor for any increase in side effects.

Epcoritamab causes the release of cytokines that may suppress the activity of CYP enzymes, and enhance the concentration of CYP substrates. This is more likely to occur after the first dose of epcoritamab and up to 14 days after the 48 mg dose.

Active ingredient: epcoritamab-byspInactive ingredients (Epkinly): acetic acid, polysorbate 80, sodium acetate, sorbitol, and Water for Injection.

Epcoritamab is manufactured under the brand name Epkinly by Genmab, a Danish biotechnology company headquartered in Copenhagen, Denmark, in collaboration with AbbVie, an American biopharmaceutical company based in North Chicago, Illinois. Other notable drugs by these companies include:

• Genmab: Darzalex - for multiple myeloma Kesimpta - for multiple sclerosis Tivdak - for cervical cancer.
• AbbVie: Humira - for various autoimmune conditions Rinvoq - for rheumatoid arthritis Skyrizi - for psoriasis Venclexta - for certain leukemias Vraylar - for schizophrenia and bipolar disorder.