KIMMTRAK (Tebentafusp)
Bispecific T-Cell Engager for Metastatic Uveal Melanoma
Quick Facts About KIMMTRAK
Key Takeaways About KIMMTRAK
- First survival benefit in metastatic uveal melanoma: KIMMTRAK is the first and only systemic therapy to demonstrate a statistically significant improvement in overall survival for metastatic uveal melanoma in a Phase 3 clinical trial
- Requires HLA-A*02:01 testing: Before starting treatment, a blood test (HLA genotyping) must confirm you carry the HLA-A*02:01 allele, as the drug only works in patients with this specific tissue type
- Cytokine release syndrome is expected: Most patients experience cytokine release syndrome (CRS), particularly after the first three infusions, requiring hospital-level monitoring for at least 16 hours after initial doses
- Weekly intravenous infusion: KIMMTRAK is given as a 15–20 minute IV infusion once per week, with a dose-escalation schedule during the first three weeks
- Specialist supervision required: Treatment must be initiated and supervised by healthcare professionals experienced in cancer treatment, in a setting equipped to manage CRS and other serious adverse reactions
What Is KIMMTRAK and What Is It Used For?
KIMMTRAK (tebentafusp) is a bispecific T-cell engager that activates the immune system to recognise and destroy cancer cells. It is used to treat adults with a rare form of eye cancer called uveal melanoma that has spread beyond the eye or cannot be surgically removed, specifically in patients who carry the HLA-A*02:01 tissue type.
KIMMTRAK contains the active substance tebentafusp, a novel immunotherapy agent manufactured by joining two distinct proteins into a single bispecific fusion molecule. One end of the molecule consists of a soluble T-cell receptor (TCR) that specifically recognises a peptide fragment of a protein called gp100 (glycoprotein 100) when it is presented on the cell surface by the HLA-A*02:01 molecule. The gp100 protein is found at high levels on the surface of uveal melanoma cells, making it an ideal target. The other end of the molecule is a single-chain variable fragment (scFv) antibody that binds to CD3, a receptor found on the surface of T cells, which are a critical component of the body’s immune defence system.
By simultaneously binding to gp100 on the tumour cell and CD3 on the T cell, KIMMTRAK physically bridges these two cell types together. This bridging action activates the T cell and directs it to kill the gp100-expressing tumour cell. Importantly, KIMMTRAK can recruit and activate any T cell in the vicinity, regardless of that T cell’s own natural receptor specificity. This mechanism is known as T-cell redirection and represents a fundamentally different approach to cancer immunotherapy compared with traditional checkpoint inhibitors.
Uveal melanoma is a rare but serious form of cancer that originates in the pigmented cells (melanocytes) of the uveal tract of the eye, which includes the iris, ciliary body, and choroid. While the primary tumour can often be treated successfully with local therapies such as radiation plaque therapy or enucleation (surgical removal of the eye), approximately 50% of patients will eventually develop metastatic disease, most commonly spreading to the liver. Prior to KIMMTRAK, no systemic therapy had demonstrated an overall survival benefit in metastatic uveal melanoma, and the prognosis was poor, with median overall survival of approximately 10–13 months.
KIMMTRAK received accelerated approval from the U.S. Food and Drug Administration (FDA) in January 2022 and conditional marketing authorisation from the European Medicines Agency (EMA) in February 2022, based on the results of the landmark IMCgp100-202 Phase 3 clinical trial. This trial demonstrated that KIMMTRAK significantly improved overall survival compared with the investigator’s choice of therapy (including pembrolizumab, ipilimumab, or dacarbazine) in previously untreated metastatic uveal melanoma patients who were HLA-A*02:01-positive.
KIMMTRAK belongs to a class of drugs known as immune mobilising monoclonal T-cell receptors against cancer (ImmTAC). It is the first ImmTAC molecule to receive regulatory approval anywhere in the world. The technology was developed by Immunocore, a biotechnology company headquartered in the United Kingdom, which specialises in developing TCR-based therapies for cancer and infectious diseases.
What Should You Know Before Receiving KIMMTRAK?
Before starting KIMMTRAK, your doctor must confirm you are HLA-A*02:01-positive through a blood test. Tell your doctor about all medical conditions, especially heart problems including QT prolongation, adrenal insufficiency, pregnancy, and breastfeeding. KIMMTRAK must not be used if you are allergic to tebentafusp or any of the other ingredients.
Contraindications
You should not receive KIMMTRAK if any of the following apply to you:
- Allergy to tebentafusp or any of the other ingredients in KIMMTRAK (citric acid monohydrate, disodium hydrogen phosphate, mannitol, trehalose, polysorbate 20, or water for injections)
- HLA-A*02:01-negative status – KIMMTRAK works only in patients who carry the specific HLA-A*02:01 tissue type, which must be confirmed by an approved HLA genotyping test before treatment begins
If you are uncertain about whether any of these conditions apply to you, speak to your doctor or nurse before receiving KIMMTRAK.
Warnings and Precautions
Tell your doctor or nurse about all your medical conditions before receiving KIMMTRAK, in particular:
- Heart problems, including changes in the heart’s electrical activity (prolonged QT interval), a history of arrhythmias, or heart failure. KIMMTRAK can affect heart rhythm, and your doctor will monitor your heart function during treatment
- Adrenal insufficiency (Addison’s disease) – if you are taking corticosteroids for this condition, your doctor may need to adjust your corticosteroid dose during KIMMTRAK treatment
- Cytokine release syndrome (CRS): Fever, dizziness, feeling faint, difficulty breathing, nausea, vomiting, fatigue, muscle or joint pain, swelling, low blood pressure, rapid heart rate, or headache
- Skin reactions: Itchy skin, rash, severe hives (itchy lumps under the skin), skin peeling, or swelling of the body and/or skin around the eyes
- Heart problems: Fast or irregular heartbeat, palpitations, shortness of breath, unsteadiness, dizziness, or chest pain
Your doctor or nurse will monitor you for signs and symptoms of these reactions during and after each dose. If you develop severe side effects, treatment may be paused temporarily and resumed once you feel better. The first three doses are always given in a hospital setting, with monitoring for at least 16 hours after each infusion.
Pregnancy and Breastfeeding
If you are pregnant, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before receiving KIMMTRAK.
Pregnancy: KIMMTRAK should not be used during pregnancy unless you and your doctor agree that the benefit of treatment outweighs the potential risks to the unborn child. If you are a woman of childbearing potential, your doctor or nurse will perform a pregnancy test before you start KIMMTRAK treatment. If you become pregnant during treatment, you must immediately inform your doctor or nurse.
Contraception: If you are a woman of childbearing potential, you must use effective contraception to prevent pregnancy during treatment with KIMMTRAK and for at least 1 week after the last dose. Discuss the most suitable forms of contraception with your doctor.
Breastfeeding: You should not breastfeed during treatment with KIMMTRAK. It is not known whether tebentafusp passes into breast milk, and a risk to the breastfed infant cannot be excluded.
Children and Adolescents
KIMMTRAK should not be given to children and adolescents under 18 years of age. This is because there is limited information on how well the medicine works and how safe it is in this age group. Uveal melanoma is extremely rare in the paediatric population, and no clinical trials have been conducted in children.
Driving and Operating Machinery
KIMMTRAK is unlikely to affect your ability to drive and use machines under normal circumstances. However, if you feel unwell during or after treatment – for example, if you experience dizziness, fatigue, or low blood pressure associated with cytokine release syndrome – you should not drive or use machines until you feel well again. Given that monitoring is required after each infusion, you should arrange for transportation home after treatment.
How Does KIMMTRAK Interact with Other Drugs?
KIMMTRAK has limited known drug–drug interactions because it is a biologic protein that is not metabolised by cytochrome P450 liver enzymes. However, patients taking corticosteroids for adrenal insufficiency may require dose adjustments. Always tell your doctor about all medications you are taking, including over-the-counter products and supplements.
Unlike many small-molecule drugs, tebentafusp is a bispecific fusion protein that is degraded by normal protein catabolism rather than hepatic cytochrome P450 enzymes. As a result, conventional pharmacokinetic drug–drug interactions are not expected. No formal drug interaction studies have been conducted with KIMMTRAK. However, there are several important clinical considerations regarding concomitant medications:
Important Clinical Considerations
| Drug / Class | Category | Clinical Concern | Recommendation |
|---|---|---|---|
| Corticosteroids (for adrenal insufficiency) | Hormone replacement | CRS may mask or worsen adrenal crisis; corticosteroid doses may be inadequate during CRS episodes | Inform your doctor; dose adjustment of corticosteroids may be needed during KIMMTRAK treatment |
| QT-prolonging medications | Various (antiarrhythmics, antibiotics, antipsychotics) | KIMMTRAK may cause QT prolongation; additive risk with other QT-prolonging drugs | Use with caution; ECG monitoring recommended; discuss all medications with your oncologist |
| Immunosuppressants | Various (e.g., cyclosporine, tacrolimus) | May theoretically reduce the immune-mediated antitumour activity of KIMMTRAK | Discuss with your oncologist before starting KIMMTRAK; avoid high-dose immunosuppression if possible |
| Systemic corticosteroids (high dose) | Anti-inflammatory | May blunt T-cell activation and reduce KIMMTRAK efficacy; used short-term for CRS management | Avoid prolonged high-dose use; short courses for CRS management are acceptable per protocol |
| Anti-hypertensive medications | Blood pressure lowering | CRS-related hypotension may be exacerbated by concurrent antihypertensive therapy | Monitor blood pressure closely during infusion days; dose adjustment may be needed on treatment days |
Because KIMMTRAK is administered in a healthcare setting under medical supervision, your treatment team will be aware of all your medications and can manage any interactions in real time. It is nonetheless important to bring a complete list of all medications, vitamins, and supplements you are taking to every treatment appointment.
There are no known interactions between KIMMTRAK and food. The pre-infusion intravenous fluid hydration that is often given before each dose does not affect the efficacy of the drug.
What Is the Correct Dosage of KIMMTRAK?
KIMMTRAK uses a dose-escalation schedule: 20 micrograms on day 1, 30 micrograms on day 8, and 68 micrograms from day 15 onwards, given weekly as an intravenous infusion over 15–20 minutes. Your doctor or nurse will administer the infusion; you will not self-administer this medicine.
KIMMTRAK is always prepared and administered by a qualified healthcare professional in a hospital or outpatient oncology setting. You may receive intravenous fluids (a drip) before each infusion to help prevent low blood pressure that may occur as a result of cytokine release syndrome.
Dose-Escalation Schedule
| Treatment Day | Dose | Volume from Vial | Setting | Monitoring |
|---|---|---|---|---|
| Day 1 | 20 micrograms | 0.10 mL | Hospital (inpatient) | At least 16 hours post-infusion |
| Day 8 | 30 micrograms | 0.15 mL | Hospital (inpatient) | At least 16 hours post-infusion |
| Day 15 | 68 micrograms | 0.34 mL | Hospital (inpatient) | At least 16 hours post-infusion |
| Day 22 onwards (weekly) | 68 micrograms | 0.34 mL | Outpatient (if tolerated) | At least 60 minutes post-infusion |
Hospital Phase (First Three Doses)
The first three doses of KIMMTRAK are always administered in a hospital (inpatient) setting. This is because cytokine release syndrome and other serious adverse reactions are most likely to occur during the dose-escalation phase. You will be monitored for at least 16 hours after each of the first three infusions for signs and symptoms of CRS, skin reactions, and cardiac events. Your vital signs (blood pressure, heart rate, temperature, and oxygen levels) will be checked regularly during this monitoring period.
Outpatient Phase (Subsequent Doses)
If the first three doses are tolerated without severe or unmanageable side effects, subsequent doses may be given in an outpatient setting. You will be monitored for at least 60 minutes after each dose. If you have been receiving KIMMTRAK in an outpatient setting for at least 3 months without any treatment interruption lasting longer than 2 weeks, the post-infusion monitoring period may be reduced to 30 minutes.
Treatment Duration
Treatment with KIMMTRAK continues for as long as your doctor determines that you are benefiting from therapy. There is no predetermined maximum duration of treatment. Your doctor will regularly assess your response to treatment and monitor for side effects to decide whether to continue, pause, or stop treatment.
Missed Dose
If you miss a scheduled KIMMTRAK infusion appointment, contact your doctor or nurse as soon as possible to arrange a new appointment. It is important to maintain the weekly treatment schedule for optimal effectiveness. Your doctor will advise you on how to resume treatment depending on how long the gap has been.
KIMMTRAK must be diluted in a 0.9% sodium chloride infusion bag containing human albumin before administration. This preparation is performed by trained healthcare professionals using aseptic technique. Closed system transfer devices (CSTDs) must not be used during preparation. The prepared infusion must be used within 4 hours at room temperature (below 30°C) or within 24 hours if refrigerated at 2–8°C.
What Are the Side Effects of KIMMTRAK?
The most common side effects of KIMMTRAK include cytokine release syndrome (CRS), skin reactions (rash, itching, skin discolouration), fatigue, fever, and changes in blood chemistry. CRS occurs in the vast majority of patients, particularly after the first three infusions, and is managed with supportive care in a monitored clinical setting.
Like all medicines, KIMMTRAK can cause side effects, although not everybody gets them. Because KIMMTRAK works by strongly activating the immune system, many of the side effects are related to this immune activation. Side effects tend to be most pronounced during the first three doses (the dose-escalation period) and generally decrease in frequency and severity with continued treatment.
- Cytokine release syndrome (CRS): Fever, dizziness, feeling faint, difficulty breathing, nausea, vomiting, fatigue, muscle or joint pain, swelling, low blood pressure, rapid heart rate, or headache. Most common after the first three infusions.
- Skin reactions: Itchy skin, widespread rash, severe hives, skin peeling, or swelling around the eyes or body. Most common after the first three infusions.
- Heart problems: Fast or irregular heartbeat, changed electrical activity of the heart (which may cause serious heart rhythm disturbances), palpitations, shortness of breath, dizziness, unsteadiness, or chest pain.
Very Common
May affect more than 1 in 10 people
- Cytokine release syndrome (CRS) – fever, chills, low blood pressure, rapid heart rate
- Decreased appetite
- Tingling, prickling, or numbness (paraesthesia)
- Cough
- Diarrhoea
- Constipation
- Indigestion (dyspepsia)
- Abdominal pain
- Chills
- Difficulty sleeping (insomnia)
- Flu-like symptoms
- Skin flushing
- High blood pressure (hypertension)
- Dry skin
- Changes in skin colour (hyperpigmentation or depigmentation)
- Skin redness (erythema)
- Decreased blood levels of phosphate, magnesium, sodium, calcium, potassium, and haemoglobin
- Elevated liver enzymes and bilirubin (potential signs of liver stress)
- Elevated blood lipase (potential sign of pancreatic stress)
- Decreased white blood cell count
- Back pain, arm or leg pain
- Fatigue and weakness
- Fever
- Skin rash and itching
Common
May affect up to 1 in 10 people
- Nose and throat infection (nasopharyngitis)
- Mouth and throat pain (oropharyngeal pain)
- Hair loss (alopecia)
- Excessive night sweats
- Anxiety
- Altered taste sensation (dysgeusia)
- Changed or irregular heartbeat (arrhythmia)
- Shortness of breath (dyspnoea)
- Muscle spasms
- Elevated blood amylase (pancreatic enzyme)
- Elevated blood creatinine (potential sign of kidney stress)
- Elevated gamma-glutamyltransferase (liver enzyme)
- Elevated white blood cell count
- Elevated alkaline phosphatase
- Elevated blood glucose
Uncommon
May affect up to 1 in 100 people
- Tumour lysis syndrome – elevated blood potassium, phosphate, and uric acid from rapidly dying cancer cells
- Chest discomfort or pain (possible sign of cardiac problems)
- Heart failure (shortness of breath, chest discomfort, swelling of legs and ankles)
- Changed electrical activity of the heart that may cause serious cardiac rhythm disturbances (QT prolongation)
Understanding Cytokine Release Syndrome (CRS)
Cytokine release syndrome is the most significant and expected side effect of KIMMTRAK therapy. It occurs because the drug activates T cells, which then release signalling molecules called cytokines into the bloodstream. This cytokine surge causes the symptoms described above. CRS is categorised by severity grade, ranging from mild (grade 1, with fever only) to life-threatening (grade 4, requiring intensive care support).
In the pivotal IMCgp100-202 clinical trial, CRS occurred in approximately 89% of patients, with the vast majority of events being grade 1 or 2. Grade 3 CRS (requiring hospitalisation or intravenous fluids) occurred in a smaller proportion of patients, and grade 4 events were rare. CRS is most common and most severe after the first dose and typically decreases in severity with each subsequent infusion. Most CRS episodes resolve within 24–48 hours with supportive care, including intravenous fluids, paracetamol (acetaminophen), and in some cases, short courses of corticosteroids.
The dose-escalation schedule (starting at 20 micrograms and increasing to the full 68 microgram dose over 3 weeks) was specifically designed to minimise the severity of CRS by gradually exposing the immune system to the drug.
How Should KIMMTRAK Be Stored?
KIMMTRAK must be stored in a refrigerator at 2–8°C, protected from light, and kept out of the reach of children. As a hospital-administered medication, storage is handled by healthcare professionals. Patients do not need to store this medicine at home.
KIMMTRAK is a specialised biologic medicine that requires careful storage and handling by pharmacy and nursing staff. The following storage conditions apply:
- Unopened vials: Store at 2–8°C (in a refrigerator). Keep the vial in the outer carton to protect from light. Do not freeze.
- Prepared infusion bag (not used immediately): May be stored at below 30°C for up to 4 hours, or at 2–8°C for up to 24 hours from the time of preparation to completion of administration.
- Do not use the medicine after the expiry date printed on the vial label and carton (EXP). The expiry date refers to the last day of the stated month.
- Do not use the medicine if you notice visible signs of deterioration such as particles or discolouration in the solution.
- Single-use vial: Each vial is for one-time use only. Do not save unused medicine for later use. Any unused product and waste material should be disposed of in accordance with local regulations.
Because KIMMTRAK is given in a clinical setting, patients will not handle or store this medicine themselves. The healthcare team is responsible for proper storage, preparation, and disposal.
What Does KIMMTRAK Contain?
Each 0.5 mL single-dose vial of KIMMTRAK contains 100 micrograms of tebentafusp as the active ingredient, along with buffering agents, stabilisers, and water for injections. The medicine is a clear, colourless to slightly yellowish solution.
Active Ingredient
The active substance is tebentafusp. Each 0.5 mL vial contains 100 micrograms of tebentafusp, a bispecific fusion protein consisting of a soluble T-cell receptor targeting gp100280-288/HLA-A*02:01 fused to an anti-CD3 single-chain variable fragment (scFv).
Other Ingredients (Excipients)
- Citric acid monohydrate (E330)
- Disodium hydrogen phosphate (E339)
- Mannitol (E421)
- Trehalose
- Polysorbate 20 (E432)
- Water for injections
This medicine contains less than 1 mmol (23 mg) sodium per mL, which means it is essentially “sodium-free”.
Appearance and Packaging
KIMMTRAK concentrate for solution for infusion (sterile concentrate) is a clear, colourless to slightly yellowish solution supplied in a single-dose glass vial. Each carton contains 1 glass vial. Before infusion, the concentrate must be diluted into a 100 mL 0.9% sodium chloride infusion bag containing human albumin.
Marketing Authorisation Holder and Manufacturer
KIMMTRAK is manufactured by ProPharma Group The Netherlands B.V. (Leiden, Netherlands) and marketed by Immunocore Ireland Limited (Dublin, Ireland). For further information about this medicine, contact Immunocore Ireland Limited at +353 1 691 5450.
Frequently Asked Questions About KIMMTRAK
KIMMTRAK (tebentafusp) is used to treat HLA-A*02:01-positive adults with unresectable or metastatic uveal melanoma, a rare form of eye cancer. It is used when the cancer has grown despite local treatment (such as radiation to the eye) or has spread to other parts of the body, most commonly the liver. KIMMTRAK is the first systemic therapy to show an overall survival benefit in this disease.
KIMMTRAK is a bispecific T-cell engager that works by physically bridging cancer cells and immune cells. One end recognises gp100, a protein abundant on uveal melanoma cells, while the other end binds CD3 on T cells. By connecting these two cell types, KIMMTRAK activates T cells to kill the tumour cells. This mechanism works regardless of the T cell’s own natural receptor specificity, effectively redirecting the immune response against the cancer.
Cytokine release syndrome (CRS) is a systemic inflammatory response caused by the activation of T cells by KIMMTRAK. Symptoms include fever, chills, low blood pressure, nausea, and fatigue. CRS is most common and most severe after the first three infusions and tends to diminish with subsequent doses. It is managed with supportive care including intravenous fluids, fever-reducing medications, and sometimes short courses of corticosteroids. The dose-escalation schedule was designed to reduce CRS severity.
KIMMTRAK is only suitable for adult patients (18 years and older) who have the HLA-A*02:01 tissue type, which is determined by a blood test. Approximately 45–50% of people of European ancestry carry this specific HLA allele. You must also have a confirmed diagnosis of unresectable or metastatic uveal melanoma. Your oncologist will determine whether KIMMTRAK is appropriate for your specific clinical situation.
KIMMTRAK treatment continues for as long as your oncologist determines that you are benefiting from therapy and the side effects are manageable. There is no predetermined maximum treatment duration. The medicine is given as a weekly intravenous infusion. In the pivotal clinical trial, some patients continued treatment for over two years. Your doctor will regularly assess your response and decide whether to continue treatment.
KIMMTRAK is not described as a cure for metastatic uveal melanoma. However, it is the first treatment to significantly improve overall survival in this disease. In the Phase 3 IMCgp100-202 trial, KIMMTRAK reduced the risk of death by 51% compared with investigator’s choice of therapy. Some patients have shown durable responses and prolonged disease control. Ongoing research is exploring ways to further improve outcomes, including combination approaches with other immunotherapy agents.
References
- Nathan P, Hassel JC, Rutkowski P, et al. Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. New England Journal of Medicine. 2021;385(13):1196-1206. doi:10.1056/NEJMoa2103485
- European Medicines Agency (EMA). KIMMTRAK (tebentafusp) – Summary of Product Characteristics (SmPC). Last updated December 2025. Available at: EMA EPAR – KIMMTRAK
- U.S. Food and Drug Administration (FDA). KIMMTRAK (tebentafusp-tebn) Prescribing Information. Revised January 2024. Available at: FDA Label
- Carvajal RD, Butler MO, Shoushtari AN, et al. Clinical and molecular response to tebentafusp in previously treated patients with metastatic uveal melanoma: a phase 2 trial. Nature Medicine. 2022;28(11):2364-2373. doi:10.1038/s41591-022-02015-7
- Piperno-Neumann S, Hassel JC, Rutkowski P, et al. Phase 3 randomized trial comparing tebentafusp with investigator’s choice in first line metastatic uveal melanoma. Journal of Clinical Oncology. 2023;41(28):4505-4515.
- ESMO Clinical Practice Guidelines: Uveal Melanoma. Annals of Oncology. 2023;34(11):970-982.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Melanoma: Uveal. Version 2.2025. Available at: NCCN Guidelines
- World Health Organization (WHO). WHO Model List of Essential Medicines, 23rd edition. 2023. Available at: WHO Essential Medicines
Editorial Team
This article has been reviewed and approved by the iMedic Medical Editorial Team, which includes board-certified specialists in oncology, immunology, and clinical pharmacology.
Content researched and written by medical writers with expertise in oncology and immuno-oncology, following GRADE evidence framework and international clinical practice guidelines (EMA, FDA, ESMO, NCCN).
Reviewed by board-certified oncologists with experience in melanoma treatment and immunotherapy. All clinical claims verified against peer-reviewed literature and regulatory documents.
Following Evidence Level 1A standards based on systematic reviews and randomised controlled trials. No commercial funding or pharmaceutical sponsorship. Independent editorial content.
This article is reviewed and updated regularly to reflect the latest clinical evidence, regulatory updates, and changes to prescribing information. Last reviewed: .