Imdelltra

Imdelltra is used to treat extensive-stage small-cell lung cancer (ES-SCLC) in adults with disease progression on or after platinum-based chemotherapy. It is given by intravenous infusion on a cyclical schedule.

Imdelltra (tarlatamab-dlle) first gained FDA approval on May 16, 2024, under the accelerated approval designation. This was upgraded to full approval on November 19, 2025, based on results from the DeLLphi-304 clinical trial (NCT05740566), which showed:

• A 40% reduction in risk of death compared to standard chemotherapy
• An extended median survival by 5+ months compared to standard chemotherapy (13.6 vs 8.3 months, P < 0.001).

There is no Imdelltra generic or biosimilar.

Imdelltra is given by a healthcare provider via an intravenous (IV) infusion through a needle placed in a vein.

• The Imdelltra infusion will take about 1 hour.
• You will receive the infusion in a clinic or hospital setting.
• Your Imdelltra treatment schedule is divided into cycles that are usually 28 days (4 weeks) long.
• Your healthcare provider will decide how many treatment cycles you will receive.

Before receiving Imdelltra, tell your healthcare provider about all of your medical conditions, including if you:

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

Pregnancy

Imdelltra may harm your unborn baby. Females who can become pregnant:

• Your healthcare provider should do a pregnancy test before you start treatment with Imdelltra
• You should use an effective form of birth control (contraception) during treatment with Imdelltra, and for 2 months after your last dose of Imdelltra
• Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with Imdelltra.

Breastfeeding

It is not known if Imdelltra passes into your breast milk. Do not breastfeed during treatment with Imdelltra and for 2 months after the last dose.

Common Side Effects

The most common side effects of Imdelltra include:

• Cytokine release syndrome (CRS), see below
• Fatigue
• Decreased appetite
• A bad or metallic taste in your mouth
• Fever
• Muscle or bone pain
• Constipation
• Nausea.

The most common severe abnormal blood test results with Imdelltra include:

• Decreased white blood cells
• Decreased sodium
• Increased uric acid.

Serious Side Effects and Warnings

Imdelltra carries a Boxed Warning for cytokine release syndrome and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS). Imdelltra can also cause other serious side effects.

Cytokine Release Syndrome (CRS)

CRS is common during treatment with Imdelltra, and can also be severe, life-threatening, or cause death. It occurs when your immune system overreacts to treatment. 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
• Low blood pressure
• Tiredness
• Fast heartbeat or dizziness
• Headache
• Shortness of breath or trouble breathing
• Nausea and vomiting
• Confusion, restlessness, or feeling anxious
• Problems with balance and movement, such as trouble walking
• Heart, liver, or kidney problems
• Blood clots or unusual bleeding, or bleeding that lasts a long time.

Due to the risk of CRS, you will receive Imdelltra on a “step-up dosing schedule”:

• The step-up dosing schedule is when you receive a smaller dose of Imdelltra on Day 1 of your firsttreatment cycle (Cycle 1).
• You will receive the full treatment dose of Imdelltra on Days 8 and 15 of Cycle 1. You will receive the full treatment dose 1 time every 2 weeks after Day 15 of Cycle 1.
• If your dose of Imdelltra is delayed for any reason, you may need to repeat the step-up dosingschedule.
• Before receiving your Days 1 and 8 doses of Cycle 1 of Imdelltra, you will be given a medicine tohelp reduce your risk of CRS. This will be given into your vein by intravenous (IV) infusion. You will also receive IV fluids after each of your Cycle 1 Days 1 and 8 doses. Your healthcare provider will decide if you need to receive medicines to help reduce your risk of CRS with future doses.

Neurologic Problems

Imdelltra can cause neurologic problems that can be severe, life-threatening, or cause death. Neurologic problems may happen days or weeks after you receive Imdelltra. 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:

• Changes in taste
• Headache
• Numbness or tingling of your hands or feet
• Dizziness
• Trouble sleeping
• Muscle weakness or numbness of your arms or legs
• Problems with walking, or loss of balance or coordination
• Trouble speaking, memory loss, or personality changes
• Confusion, feeling disoriented, slow thinking, or not being able to think clearly
• Fainting or loss of consciousness
• Seizures
• Shaking (tremors)
• Sleepiness
• Feeling like you have no energy.

Monitoring for CRS and neurologic problems

Due to the risk of CRS and neurologic problems, you will receive the following monitoring during treatment with Imdelltra:

• For Day 1 and Day 8 of Cycle 1 doses, your healthcare provider will monitor you for 6 to 8 hours from the start of the Imdelltra infusion in an appropriate healthcare setting that can manage these side effects.
• You should remain within 1 hour of an appropriate healthcare setting for a total of 48 hours from the start of the Imdelltra infusion after your Day 1 and Day 8 of Cycle 1 doses, and be accompanied by a caregiver.
• On Day 2 and Day 9 of Cycle 1, your healthcare provider will check you for any signs or symptoms, including checking your temperature, breathing, heart rate, blood pressure, and oxygen levels.
• For Day 15 of Cycle 1 and Cycle 2 doses, your healthcare provider will watch you for 6 to 8 hours after the Imdelltra infusion.
• For Cycle 3 and Cycle 4 doses, your healthcare provider will watch you for 3 to 4 hours after the Imdelltra infusion.
• For Cycle 5 and later doses, your healthcare provider will watch you for 2 hours after the Imdelltra infusion.

Your healthcare provider will monitor you for signs and symptoms of CRS and neurologic problems during treatment with Imdelltra, and treat you as needed. You may be hospitalized if you develop these symptoms. Your provider may temporarily or completely stop your treatment with Imdelltra if you develop CRS or neurologic problems.Note: Extended monitoring in a healthcare setting is not required unless the patient had Grade 2 or higher CRS, ICANS, or neurologic toxicity during prior treatment. If a patient does have a Grade 2 or higher event, then 22 to 24 hours or monitoring is requitred for the next dose.

Low Blood Cell Counts (Cytopenia)

Decreased blood cell counts can be severe and may include the following:

• 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.

Infections

Imdelltra can cause serious infections that can be life-threatening and cause death. Your healthcare provider will check you for signs and symptoms of infection before and during treatment with Imdelltra.

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 or runny nose
• Pain during urination
• Feeling weak or generally unwell
• Yeast infections in the mouth or other areas.

Liver Problems

Imdelltra can cause increased liver enzymes and bilirubin in your blood. These increases can happen with or without you also having CRS. Tell your healthcare provider right away if you develop any signs or symptoms of liver problems, including:

• Tiredness
• Loss of appetite
• Pain in your right upper stomach area (abdomen)
• Dark urine
• Yellowing of your skin or the white part of your eyes.

Allergic Reactions

Imdelltra can cause allergic reactions that can be severe. Go to the nearest emergency room or get medical help right away if you develop any signs or symptoms of a severe allergic reaction during treatment with Imdelltra, including:

• Shortness of breath or trouble breathing
• Pain or tightness in your chest and back
• Wheezing
• Coughing
• Feeling lightheaded or dizzy
• Rash.

Notes:

Your healthcare provider will do bloodwork before you start and during treatment with Imdelltra. Your healthcare provider will monitor you for signs or symptoms of these serious side effects during treatment and may temporarily or completely stop treatment with Imdelltra if you develop certain serious side effects.

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

Imdelltra (tarlatamab-dlle) has two "arms" that work together. One "arm" binds to DLL3 proteins found on the surface of cells, including small cell lung cancer cells, while the other binds to CD3 proteins expressed on the surface of T cells (part of the immune system). It is a targeted immunotherapy treatment, not chemotherapy.

Imdelltra's mechanism involves bringing DLL3 proteins and T cells together, causing T-cell activation, release of inflammatory cytokines, and lysis (rupturing of the cell membrane), causing death of DLL3-expressing cells.

Imdelltra belongs to the drug class called bispecific T-cell engagers (BiTEs). It may also be called a bispecific delta-like ligand 3 (DLL3)-directed CD3 T-cell engager.

Imdelltra is administered according to a step-up dosing schedule to reduce the risk of cytokine release syndrome.

Adult Dose of Imdelltra for ES-SCLC

Cycle 1

• Day 1: 1mg
• Day 2: Your healthcare provider will check you for any signs or symptoms, including checking your temperature, breathing, heart rate, blood pressure, and oxygen levels.
• Day 8: 10 mg Monitor patients for 6 to 8 hours from the start of the Imdelltra infusion in an appropriate healthcare setting that can manage these side effects. You should remain within 1 hour of an appropriate healthcare setting for a total of 48 hours from the start of the Imdelltra infusion after your Day 1 and Day 8 of Cycle 1 doses, and be accompanied by a caregiver.
• Day 9: Your healthcare provider will check you for any signs or symptoms, including checking your temperature, breathing, heart rate, blood pressure, and oxygen levels.
• Day 15: 10 mg Observe patients for 6-8 hours post-Imdelltra infusion. Extended monitoring in a healthcare setting is not required unless the patient experiences Grade ≥ 2 CRS, ICANS, or neurological toxicity during prior treatments.

Recommended concomitant medications before and after Cycle 1, Days 1 and 8:

• Dexamethasone 8 mg IV within 1 hour before the Cycle 1 Day 1 and Day 8 infusions, plus 1 liter of normal saline IV over 2 to 4 hours immediately after each of those infusions.

Cycle 2

• Day 1: 10 mg
• Day 15: 10 mg Observe patients for 6-8 hours post-Imdelltra infusion on Days 1 and 15. Extended monitoring in a healthcare setting is not required unless the patient experiences Grade ≥ 2 CRS, ICANS, or neurological toxicity during prior treatments.

Cycles 3 and 4

• Day 1: 10 mg
• Day 15: 10 mg Observe patients for 3-4 hours post-Imdelltra infusion on Days 1 and 15. Extended monitoring in a healthcare setting is not required unless the patient experiences Grade ≥ 2 CRS, ICANS, or neurological toxicity during prior treatments.

Cycles 5 and subsequent infusions

• Day 1: 10 mg
• Day 15: 10 mg Observe patients for 2 hours post-Imdelltra infusion on Days 1 and 15. Extended monitoring in a healthcare setting is not required unless the patient experiences Grade ≥ 2 CRS, ICANS, or neurological toxicity during prior treatments.

• Do not drive, operate heavy or potentially dangerous machinery, or do other dangerous activities, including work-related activities, during treatment with Imdelltra 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 neurologic problems.

Active ingredients: tarlatamab-dlle

Inactive ingredients: glutamic acid, polysorbate 80, sucrose, and sodium hydroxide.

Inactive ingredients of IV solution stabilizer: citric acid monohydrate, lysine hydrochloride, polysorbate 80, sodium hydroxide, and water for Injection.

Imdelltra (tarlatamab-dlle) is available in 1mg and 10mg vials that require reconstitution and further dilution.

Imdelltra is manufactured by Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799.