Neither checkpoint inhibitors nor other systemic therapies for mCM are FDA approved in mUM.2-4
Patients have faced a dismal prognosis, with a post-diagnosis median survival of approximately 9-16 months.2,5-9 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend enrollment in an investigational clinical trial, if appropriate, as a preferred option.1
* Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Melanoma: Uveal V.2.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed May 6, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org.
* Based on in vitro and in vivo studies.2,10,13
† Provide a whole blood specimen to a CLIA-certified diagnostic lab and request a high-resolution HLA test.14,15
Improved OS was seen in a pivotal phase 3 trial of 378 HLA-A*02:01-positive adult patients with mUM treated with KIMMTRAK in first-line (HR = 0.51; 95% CI, 0.37-0.71; P < 0.0001), compared with investigator’s choice of pembrolizumab, ipilimumab, or dacarbazine.
In clinical trials, patients stopped treatment for disease progression,* unless they were otherwise deriving benefit, or for unacceptable toxicity.2
* Two scans were required to confirm progression.16 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.17
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.2,7,18
HLA-A, human leukocyte antigen-A; LDH, lactate dehydrogenase; ULN, upper limit of normal.
Radiologic assessment every 12 weeks.
* 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).
KIMMTRAK adverse events were predictable and manageable† with 3.3% of patients discontinuing treatment due to adverse events (AEs)2,7
† CRS symptoms were generally reversible and managed with IV fluids, NSAIDs, a single dose of corticosteroids, oxygen, and rarely, a vasopressor.2,7 Monitor fluid status, vital signs, and oxygenation level and provide appropriate therapy.2
Incidence of treatment-related AEs by week during treatment with KIMMTRAK7
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) = 227.7
CRS represents algorithmic identification of cases based on ASTCT grading criteria (Lee at al. 2019). Rash represents a composite of multiple related terms.2
Adverse reactions occurring in ≥20% of patients receiving KIMMTRAK in study IMCgp100-2022
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.
Rash tended to occur early in treatment, decreased in incidence and severity, and was associated with 27-month median overall survival (mOS)2,7
KIMMTRAK adverse events were generally predictable, manageable, and consistent with the proposed mechanism of action of KIMMTRAK2,7
CRS was observed following administration of KIMMTRAK2,7,16
CRS symptoms were generally reversible and managed with IV fluids, NSAIDs, a single dose of corticosteroids, oxygen, and rarely, a vasopressor.2,7 Monitor fluid status, vital signs, and oxygenation level and provide appropriate therapy.2
Skin reactions occurred in 91% of patients treated with KIMMTRAK2
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.2
Liver enzyme elevations were seen in 65% of patients treated with KIMMTRAK, with approximately 22% being grade 3-42
Monitor ALT, AST, and total blood bilirubin prior to the start of and during treatment with KIMMTRAK. Withhold KIMMTRAK according to severity.16
Monitor patients during the infusion and for at least 16 hours after administration of each of the first 3 doses of KIMMTRAK, as AEs related to rash or CRS are likely to occur during this time frame.2
After the first 3 doses, if the patient has not had hypotension requiring medical intervention with their most recent dose, KIMMTRAK can be administered in the outpatient setting (with a required minimum of 30 minutes of monitoring after administration).2
The starting dose is 20 mcg for week 1. The dose increases to 30 mcg for week 2 and 68 mcg for weeks 3 and beyond.
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.
A dedicated support system and educational resource
Coordination
of care
Financial and insurance assistance
Help with patient
and site of care
coordination
Patients must be HLA-A*02:01 positive to be eligible for KIMMTRAK. There are HLA tests using whole blood that report to the fourth digit available at CLIA-certified laboratories. 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.
Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Ut enim ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat.
Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum.
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. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines*) for Melanoma: Uveal V.2.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed May 6, 2022. 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 2. Kimmtrak. Package insert. Immunocore Ltd; 2022. 3. FDA Approved Drugs. Aim at Melanoma Foundation. Accessed May 25, 2022. https://www.aimatmelanoma.org/how-melanoma-is-treated/fda-approved-drugs/ 4. National Library of Medicine DailyMed. Accessed 23 August 2022. httos://dailymed.nlm.nih.gov/dailymed/index.cfm 5. Pandiani C, Béranger GE, Leclerc J, Ballotti R, Bertolotto C. Focus on cutaneous and uveal melanoma specificities. Genes Dev. 2017;31(8):724-743. doi:10.1101/gad.296962.117 6. Rantala ES, Herberg M, Kivelä TT. Overall survival after treatment for metastatic uveal melanoma: a systematic review and meta-analysis. Melanoma Res. Published online. 2019:29(6):561-568. doi:10.1097/CMR.0000000000000575 7. 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 8. 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 Onco. 2019;30(8):1370-1380. do:10.1093/annonc/mdz176 9. Yang J, Manson DK, Marr BP, Carvajal RD. Treatment of uveal melanoma: where are we now? Ther Adv Med Oncol. 2018;10:1758834018757175. doi:10.1177/1758834018757175 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 (IMCqp100) redirected CD8+ and CD4+T cells. Immunology. 2017:152(3):425-438. doi: 10.1111/mm.12779 14. Tiercy JM. How to select the best available related or unrelated donor of hematopoietic stem cells? Haematologica. 2016;101(6):680-687. do:10.3324/haematol.2015 15. Nunes E, Heslop H, Fernandez-Vina M, et al. Definitions of histocompatibility typing terms. Blood. 2011:118(23):e180-e183. do:10.1182/blood-2011-05-353490 16. Data on file. Immunocore Ltd. 17. 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)(suppl):1196-1206. doi:10.1056/NEJMoa2103485 18. 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.