Epkinly is a prescription medicine used to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL).

Epkinly contains epcoritamab-bysp, a new type of cancer treatment called a bispecific CD20-directed CD3 T-cell engager. It is designed to work by directing cytotoxic T-cells selectively to tumors to elicit an immune response towards the malignant cells.

Epcoritamab-bysp works in the treatment of DLBCL by binding to CD3 on T-cells and CD20 on B-cells to induce T-cell mediated killing of lymphoma B cells.

What is Epkinly used to treat?

Epkinly is used to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma that is relapsed (has come back) or refractory did (not respond to previous treatment), and who have already received 2 or more treatments for their cancer.

DLBCL is the most common form of non-Hodgkin's lymphoma. DLBCL is an aggressive, fast-growing B-cell lymphoma characterized by rapidly growing tumors in the lymph nodes, spleen, liver, bone marrow, or other tissues and organs. It is caused by mutations in the B-cells, which are lymphocytes that make antibodies to fight infections in the body.

It is not known if this medicine is safe and effective in children.

Epkinly can cause serious side effects, including:

Cytokine Release Syndrome (CRS). CRS is common during treatment and can also be serious or life-threatening. Tell your healthcare provider or get medical help right away if you develop any signs or symptoms of CRS, including:

• fever of 100.4°F (38°C) or higher
• dizziness or light-headedness
• trouble breathing
• chills
• fast heartbeat
• feeling anxious
• headache
• confusion
• shaking (tremors)
• problems with balance and movement, such as trouble walking

Due to the risk of CRS, you will receive treatment on a "step-up dosing schedule".

• The step-up dosing schedule is when you receive smaller "step-up" doses on Day 1 and Day 8 of your first cycle of treatment (Cycle 1).
• You will receive your first full dose on Day 15 of Cycle 1.
• If your dose is delayed for any reason, you may need to repeat the "step-up dosing schedule".
• Before each dose in Cycle 1, you will receive medicines to help reduce your risk of CRS. Your healthcare provider will decide if you need to receive medicine to help reduce your risk of CRS with future cycles.
• See How will I receive Epkinly? for more information about how you will receive this medicine.

Neurologic Problems (Immune Effector Cell-Associated Neurotoxicity Syndrome or ICANS). Epkinly can cause serious neurologic problems that can be life-threatening and lead to death. Neurologic problems may happen days or weeks after you receive this medicine. Your healthcare provider may refer you to a healthcare provider who specializes in neurologic problems. Tell your healthcare provider right away if you develop any signs or symptoms of neurologic problems, including:

• trouble speaking or writing
• confusion and disorientation
• drowsiness
• tiredness or lack of energy
• muscle weakness
• shaking (tremors)
• seizures
• memory loss

Due to the risk of CRS and neurologic problems, you should be hospitalized for 24 hours after receiving your first full dose on Day 15 of Cycle 1. Your healthcare provider will monitor you for signs and symptoms of CRS and neurologic problems during treatment, as well as other side effects and treat you if needed. Your healthcare provider may temporarily stop or completely stop your treatment if you develop CRS, neurologic problems, or any other side effects that are severe.

See Epkinly side effects for more information about side effects.

• Epkinly will be given to you by your healthcare provider as an injection under your skin (subcutaneous injection), usually in the lower part of your stomach-area (abdomen) or thigh.
• Your treatment schedule is divided into cycles that are usually 28 days (4 weeks) long.
• Epkinly is usually given every week during Cycles 1 to 3, every 2 weeks during Cycles 4 to 9, and every 4 weeks starting with Cycle 10.
• Your healthcare provider will decide how many treatment cycles you will receive.
• See Important information for more information about receiving this medicine.

Usual Adult Dose for Diffuse Large B-cell Lymphoma (DLBCL)

* Cycle = 28 days

Comments:
- patients should be hospitalized for 24 hours after administration of the Cycle 1 Day 15 dosage of 48 mg.
- administer premedications and prophylaxis as recommended. Premedications for the first cycle include prednisolone or dexamethasone or equivalent, diphenhydramine or equivalent, and acetaminophen. Premedications for the remaining cycles include prednisolone or dexamethasone or equivalent.
- dosages of 0.16 mg and 0.8 mg require dilution prior to administration.

Use:
- 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. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

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

• have an infection.

Pregnancy

Tell your healthcare provider if you are pregnant or plan to become pregnant. This medicine may cause harm your unborn baby.

Females who are able to 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

Tell your healthcare provider if you are breastfeeding or plan to breastfeed.

It is not known if this medicine passes into your breast milk. Do not breastfeed during treatment and for 4 months after your last dose.

Do not drive, operate heavy machinery, or do other dangerous activities if you develop dizziness, confusion, tremors, sleepiness, or any other symptoms that impair consciousness until your signs and symptoms go away. These may be signs and symptoms of CRS or neurologic problems.

See Important information more information about signs and symptoms of CRS and neurologic problems.

Epkinly can cause serious side effects, including:

• See Important information.
• Infections. Epkinly can cause serious infections that may lead to death. Your healthcare provider will check you for signs and symptoms of infection before and during treatment with Epkinly. Tell your healthcare provider right away if you develop any signs or symptoms of infection during treatment, including:
  • fever of 100.4°F (38°C) or higher
  • cough
  • chest pain
  • tiredness
  • shortness of breath
  • painful rash
  • sore throat
  • pain during urination
  • feeling weak or generally unwell
• Low blood cell counts. Low blood cell counts are common during treatment, and can also be serious or severe. Your healthcare provider will check your blood cell counts during treatment.
  Epkinly may cause the following low blood cell counts:
  • low white blood cell counts (neutropenia). Low white blood cells can increase your risk for infection.
  • low red blood cell counts (anemia). Low red blood cells can cause tiredness and shortness of breath.
  • low platelet counts (thrombocytopenia). Low platelet counts can cause bruising or bleeding problems.

Your healthcare provider may temporarily stop or completely stop treatment if you develop certain side effects.

The most common side effects of Epkinly include:

• tiredness
• muscle and bone pain
• injection site reactions
• fever
• stomach-area (abdominal) pain
• nausea
• diarrhea

These are not all the possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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