NCCN category 1 preferred treatment option8,*
Tebentafusp-tebn (KIMMTRAK) is a category 1* preferred treatment option for HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM).8
This recommendation is based on the published phase 3 trial data, which evaluated tebentafusp-tebn overall survival benefit vs investigator's choice.9,†
* Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate. Referenced with permission from NCCN.
† Investigator's choice: checkpoint inhibitors (pembrolizumab and ipilimumab) or chemotherapy (dacarbazine).
Consider a blood test for your patients with mUM to determine their HLA status and if KIMMTRAK is right for them.9 Click here to learn more.
MECHANISM OF ACTION
Mechanism of action
KIMMTRAK is a first-in-class T cell engager directed against mUM9,*
- KIMMTRAK is a bispecific T cell engager that redirects the immune system to target and kill gp100-expressing uveal melanoma tumor cells. Gp100 is expressed via HLA-A*02:01 on most uveal melanoma cells9,10
- KIMMTRAK has 1 million–fold greater affinity for gp100 presented by HLA-A*02:01 than natural T cell receptors11,12
- KIMMTRAK binds to uveal melanoma cells and cytotoxic T cells, forming an immune synapse9
- The T cells become activated, releasing cytokines to attract more T cells and lytic granules to contribute to tumor cell death; normal melanocytes could also be targeted9,10,13
* Based on in vitro and in vivo studies.9,10,13
STUDY RESULTS
Largest phase 3 pivotal trial in mUM evaluated first-line treatment with KIMMTRAK vs investigator’s choice (IC)9,*
Primary end point: First-line treatment with KIMMTRAK significantly extended median overall survival (mOS) by 6 months vs IC9,14,*
HR = 0.51 (95% CI, 0.37-0.71; P < 0.0001)
≈50% reduction in the risk of death9,14
At the time of the data cutoff for the first interim analysis, median duration of follow-up was 14.1 months.14
CI, confidence interval; HR, hazard ratio.
* Investigator’s choice: checkpoint inhibitors (pembrolizumab and ipilimumab) or chemotherapy (dacarbazine).9,14
Overall survival at 3-year extended follow-up analysis1
27.4% of patients were alive at 3 years with KIMMTRAK vs 17.8% with investigator’s choice*
No new safety signals were identified at the 3-year follow-up analysis.1
- Median duration of follow-up: 43.3 months (minimum follow-up: 36 months).1
- The mOS was 21.6 months (95% CI, 19.0-24.3) in the KIMMTRAK group vs 16.9 months (95% CI, 12.9-19.5) in the investigator’s choice group.1
- The planned exploratory 3-year overall survival analysis occurred after the protocol-specified final analysis and was not tested for statistical significance. No statistical conclusions can be drawn.1
* Investigator’s choice: checkpoint inhibitors (pembrolizumab and ipilimumab) or chemotherapy (dacarbazine).1
In the primary analysis, 43% of patients (109 of 252) received treatment with KIMMTRAK beyond initial progression, with no new safety signals identified. Median duration of KIMMTRAK treatment beyond initial progression was 8 weeks. Of the total KIMMTRAK infusions during the study, 22% were administered after initial progression15
In clinical trials, patients stopped treatment for disease progression,* unless they were otherwise deriving benefit, or for unacceptable toxicity.9
* Two scans were required to confirm progression.15 Further progressive disease warranting treatment discontinuation is defined as ANY of the following observed at least 4 weeks post initial progressive disease assessment: an additional >20% increase in tumor burden (with an absolute increase of >5 mm), unequivocal progressive disease of nontarget lesion, or new nonmeasurable lesions.15
Largest phase 3 clinical trial in mUM compared KIMMTRAK to checkpoint inhibitors or chemotherapy in first-line9
An international, multicenter, pivotal, phase 3, 2:1 randomized, controlled trial of 378 HLA-A*02:01-positive adult patients with metastatic uveal melanoma compared KIMMTRAK with investigator’s choice of pembrolizumab, ipilimumab, or dacarbazine.9,14,16
HLA-A, human leukocyte antigen-A; LDH, lactate dehydrogenase; ULN, upper limit of normal.
Radiologic assessment every 12 weeks.
Primary end point9
- Overall survival (OS)
Secondary end points9,16
- Progression-free survival (PFS)9
- Objective response rate (ORR)9
- Duration of response (DOR)16
- Disease control rate (DCR)16
- Stable disease (SD)16
SAFETY
Low 3.3% discontinuation rate in the primary analysis with KIMMTRAK9
KIMMTRAK adverse events were predictable and manageable* with 3.3% of patients discontinuing treatment due to adverse events (AEs)9,14
- In clinical trials, cytokine release syndrome (CRS), skin reactions, and elevated liver enzymes occurred following KIMMTRAK infusion.9 These events decreased in frequency and severity after the first 3 doses14
- The most common adverse reactions (≥30%) in patients who received KIMMTRAK were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting9
* CRS symptoms were generally reversible and managed with IV fluids, NSAIDs, a single dose of corticosteroids, oxygen, and rarely, a vasopressor.9,14 Monitor fluid status, vital signs, and oxygenation level and provide appropriate therapy.9
Incidence of treatment-related AEs by week during treatment with KIMMTRAK14
Number of patients in week 1 (dose 1) = 245, week 2 (dose 2) = 233, week 3 (dose 3) = 232, week 4 (dose 4) = 226, and week 8 (dose 8) = 227.14
CRS represents algorithmic identification of cases based on ASTCT grading criteria (Lee at al. 2019). Rash represents a composite of multiple related terms.9
Adverse reactions occurring in ≥20% of patients receiving KIMMTRAK in study IMCgp100-2029
- Represents algorithmic identification of CRS cases based on ASTCT grading criteria (Lee et al. 2019).
- Represents a composite of multiple related terms.
Clinically relevant adverse reactions occurring in <20% of patients who received KIMMTRAK included back pain, decreased appetite, constipation, hypertension, tachycardia or sinus tachycardia, dyspnea, paresthesia, dizziness, flushing, muscle spasms, myalgia, pain in extremity, alopecia, skin hyperpigmentation, influenza-like illness, oropharyngeal pain, and night sweats.9
Rash tended to occur early in treatment, decreased in incidence and severity, and was associated with 27-month median overall survival (mOS)9,14
- Severity and frequency of rash generally decreased following each of the first 3 infusions14
- Rash is thought to be due to on-target off-tumor activity of KIMMTRAK against gp100-expressing healthy melanocytes in skin, consistent with the proposed mechanism of action9,14
- Rash is not an independent predictor of overall survival; most patients will have a rash at some point during treatment, and some patients without a rash may also benefit14
DOSING AND ADMINISTRATION
KIMMTRAK is administered once weekly via continuous IV infusion over 15‑20 minutes9
Adequate hydration/euvolemic status prior to starting KIMMTRAK is advised
- If patient has not had a ≥grade 2 cytokine release syndrome adverse event with their previous dose.15
- If patient has not had hypotension requiring medical intervention with their most recent dose.9
- Adjustment in what to monitor and at what frequency can be made using clinical judgment or by institutional standards. Recommendations above based on clinical trial protocol.17
CRS management recommendations
No dosage reduction for KIMMTRAK is recommended. For specific dosage modifications please refer to Section 2.3, Table 1 in full Prescribing Information9
A rise in temperature is generally the first sign of CRS, occurring earlier than drops in blood pressure.9 Once fever is detected, patients should be monitored more closely for changes in other vital signs like pulse rate, respiratory rate, and blood pressure.9 Consider managing symptoms early to help prevent CRS from escalating.
Patients who may be sensitive to manifestations of CRS, such as hypotension, tachycardia, or hypoxia, or the use of intravenous fluids to manage CRS, should be carefully assessed prior to starting KIMMTRAK. Ensure patients are euvolemic prior to initiating KIMMTRAK infusions.9
Rash management recommendations
Rash occurred in 83% of patients.9 Rash was often described as closer to symptoms of a sunburn than a typical rash.15
Rash could cause all or more of the body to turn red, and the skin to be sore, itchy, and peel. It can manifest differently in different patients.15
Treatment guide:
dosing and AE monitoring and management
DownloadPharmacist dosing,
preparation, and AE management guide
Pharmacist KIMMTRAK
preparation video
Possible adverse reactions
PATIENT SUPPORT
Personalized support for your KIMMTRAK patients
KIMMTRAK CONNECT® offers proactive services and support tailored to your patients' individual needs. Each patient is paired with a dedicated nurse case manager, who provides one-on-one guidance throughout the treatment journey.
Watch this video to learn more about what KIMMTRAK CONNECT has to offer.
KIMMTRAK CONNECT provides:
Customized
support
Financial
assistance
Care
coordination
RESOURCES AND VIDEOS
Expert perspectives on KIMMTRAK in mUM
OS benefit and
treatment duration
Watch videoDosing and
administration
AE management
and monitoring
How to get KIMMTRAK for your patients
Verify HLA-A*02:01 status9
HLA status is determined by a simple blood test. Provide a whole blood specimen to your lab and request a high-resolution HLA test (ie, to the fourth digit). Information on FDA-approved tests is available at www.fda.gov/companiondiagnostics.
Download the HLA fact sheet to learn more about testing your patients.
Encourage patients to enroll in KIMMTRAK CONNECT
Download the KIMMTRAK CONNECT brochure for patients and help them enroll and access this no-cost support program that provides personalized guidance from financial assistance to scheduling appointments to educational materials.
Get billing and coding information for reimbursement
Download this handy guide to filing claims and reimbursement for KIMMTRAK. Find ICD-10, CPT, HCPCS, and NDC codes, sample forms, and much more.
Contact a specialty distributor
Download this information sheet to find specialty distributors that provide KIMMTRAK, dosing information, and product codes and descriptions.
Indication and Important Safety Information Including Boxed Warning
Indication
KIMMTRAK is a bispecific gp100 peptide-HLA-directed CD3 T cell engager indicated for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma.
Important Safety Information Including Boxed Warning
WARNING: CYTOKINE RELEASE SYNDROME
Cytokine Release Syndrome (CRS), which may be serious or life-threatening, occurred in patients receiving KIMMTRAK. Monitor for at least 16 hours following first three infusions and then as clinically indicated. Manifestations of CRS may include fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, and headache. CRS occurred in 89% of patients who received KIMMTRAK with 0.8% being grade 3 or 4. Ensure immediate access to medications and resuscitative equipment to manage CRS. Ensure patients are euvolemic prior to initiating the infusions. Closely monitor patients for signs or symptoms of CRS following infusions of KIMMTRAK. Monitor fluid status, vital signs, and oxygenation level and provide appropriate therapy. Withhold or discontinue KIMMTRAK depending on persistence and severity of CRS.
Skin Reactions
Skin reactions, including rash, pruritus, and cutaneous edema occurred in 91% of patients treated with KIMMTRAK. Monitor patients for skin reactions. If skin reactions occur, treat with antihistamine and topical or systemic steroids based on persistence and severity of symptoms. Withhold or permanently discontinue KIMMTRAK depending on the severity of skin reactions.
Elevated Liver Enzymes
Elevations in liver enzymes occurred in 65% of patients treated with KIMMTRAK. Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total blood bilirubin prior to the start of and during treatment with KIMMTRAK. Withhold KIMMTRAK according to severity.
Embryo-Fetal Toxicity
KIMMTRAK may cause fetal harm. Advise pregnant patients of potential risk to the fetus and patients of reproductive potential to use effective contraception during treatment with KIMMTRAK and 1 week after the last dose.
The most common adverse reactions (≥30%) in patients who received KIMMTRAK were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. The most common (≥50%) laboratory abnormalities were decreased lymphocyte count, increased creatinine, increased glucose, increased AST, increased ALT, decreased hemoglobin, and decreased phosphate.
Please see full Prescribing Information, including BOXED WARNING for CRS.
Important Safety Information Including Boxed Warning
WARNING: CYTOKINE RELEASE SYNDROME
Cytokine Release Syndrome (CRS), which may be serious or life-threatening, occurred in patients receiving KIMMTRAK. Monitor for at least 16 hours following first three infusions and then as clinically indicated.
Important Safety Information Including Boxed Warning
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References: Content to come
Indication
KIMMTRAK is a bispecific gp100 peptide-HLA-directed CD3 T cell engager indicated for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma.
Important Safety Information Including Boxed Warning
WARNING: CYTOKINE RELEASE SYNDROME
Cytokine Release Syndrome (CRS), which may be serious or life-threatening, occurred in patients receiving KIMMTRAK. Monitor for at least 16 hours following first three infusions and then as clinically indicated.
References: 1. Hassel JC, Piperno-Neumann S, Rutkowski P, et al. Three-year overall survival with tebentafusp in metastatic uveal melanoma. N Engl J Med. Published online October 21, 2023. doi:10.1056/NEJMoa2304753 2. Khoja L, Atenafu EG, Suciu S, et al. Meta-analysis in metastatic uveal melanoma to determine progression free and overall survival benchmarks: an International Rare Cancers Initiative (IRCI) ocular melanoma study. Ann Oncol. 2019;30(8):1370-1380. doi:10.1093/annonc/mdz176 3. Rantala ES, Hernberg M, Kivelä TT. Overall survival after treatment for metastatic uveal melanoma: a systematic review and meta-analysis. Melanoma Res. 2019;29(6):561-568. doi:10.1097/CMR.0000000000000575 4. Carvajal RD, Sacco JJ, Jager MJ, et al. Advances in the clinical management of uveal melanoma. Nat Rev Clin Oncol. 2023;20(2):99-115. doi: 10.1038/s41571-022-00714-1 5. Augsburger JJ, Corrêa ZM, Shaikh AH. Effectiveness of treatments for metastatic uveal melanoma. Am J Ophthalmol. 2009;148(1):119-127. doi:10.1016/j.ajo.2009.01.023 6. Carvajal RD, Schwartz GK, Tezel T, et al. Metastatic disease from uveal melanoma: treatment options and future prospects. Br J Ophthalmol. 2017;101(1):38-44. doi:10.1136/bjophthalmol-2016-309034 7. Petzold A, Steeb T, Wessely A, et al. Is tebentafusp superior to combined immune checkpoint blockade and other systemic treatments in metastatic uveal melanoma? A comparative efficacy analysis with population adjustment. Cancer Treat Rev. 2023;115:102543. doi:10.1016/j.ctrv.2023.102543 8. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Melanoma: Uveal V.1.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed May 4, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 9. Kimmtrak. Package insert. Immunocore Ltd; 2022. 10. Middleton MR, McAlpine C, Woodcock VK, et al. Tebentafusp, a TCR/anti-CD3 bispecific fusion protein targeting gp100, potently activated antitumor immune responses in patients with metastatic melanoma. Clin Cancer Res. 2020;26(22):5869-5878. doi:10.1158/1078-0432.CCR-20-1247 11. Damato BE, Dukes J, Goodall H, Carvajal RD. Tebentafusp: T cell redirection for the treatment of metastatic uveal melanoma. Cancers (Basel). 2019;11(7):971. doi:10.3390/cancers11070971 12. Oates J, Hassan NJ, Jakobsen BK. ImmTACs for targeted cancer therapy: why, what, how, and which. Mol Immunol. 2015;67(2, pt A):67-74. doi:10.1016/j.molimm.2015.01.024 13. Boudousquie C, Bossi G, Hurst JM, et al. Polyfunctional response by ImmTAC (IMCgp100) redirected CD8+ and CD4+T cells. Immunology. 2017:152(3):425-438. doi:10.1111/imm.12779 14. Nathan P, Hassel JC, Rutkowski P, et al; IMCgp100-202 Investigators. Overall survival benefit with tebentafusp in metastatic uveal melanoma. N Engl J Med. 2021;385(13):1196-1206. doi:10.1056/NEJMoa2103485 15. Data on file. Immunocore. 16. Safety and efficacy of IMCgp100 versus investigator choice in advanced uveal melanoma. ClinicalTrials.gov identifier: NCT03070392. Published March 3, 2017. Updated March 21, 2022. Accessed August 31, 2022. 17. Protocol for: Nathan P, Hassel JC, Rutkowski P, et al; IMCgp100-202 Investigators. Overall survival benefit with tebentafusp in metastatic uveal melanoma. N Engl J Med. 2021;385:1196-1206. doi:10.1056/NEJMoa2103485 18. Hassel JC, Rutkowski P, Baurain JF, et al. Co-primary endpoint of overall survival for tebentafusp (tebe)-induced rash in a phase 3 randomized trial comparing tebe versus investigator’s choice (IC) in first-line metastatic uveal melanoma. J Clin Oncol. 2021;39(15)(suppl):9527. doi:10.1200/JCO.2021.39.15_suppl.9527