* 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).
* Based on in vitro and in vivo studies.9,10,13
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
27.4% of patients were alive at 3 years with KIMMTRAK vs 17.8% with investigator’s choice*
* Investigator’s choice: checkpoint inhibitors (pembrolizumab and ipilimumab) or chemotherapy (dacarbazine).1
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
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.
KIMMTRAK adverse events were predictable and manageable* with 3.3% of patients discontinuing treatment due to adverse events (AEs)9,14
* 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
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
Adequate hydration/euvolemic status prior to starting KIMMTRAK is advised
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 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
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.
Customized
support
Financial
assistance
Care
coordination
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.
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.
Download this handy guide to filing claims and reimbursement for KIMMTRAK. Find ICD-10, CPT, HCPCS, and NDC codes, sample forms, and much more.
Download this information sheet to find specialty distributors that provide KIMMTRAK, dosing information, and product codes and descriptions.
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.
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, 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.
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.
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.
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.
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References: Content to come
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.
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