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Tebentafusp-tebn is a Category 1 Preferred Treatment option by the National Comprehensive Cancer Network® (NCCN®)1
6-month improvement in median overall survival in metastatic uveal melanoma (mUM) in first-line
See the study
Historically, there have been no FDA-approved treatments indicated for mUM—until now2-4
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
Now tebentafusp-tebn (KIMMTRAK) is included as a category 1* preferred treatment option for HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma.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.
MECHANISM OF ACTION
Proposed mechanism of action
KIMMTRAK is a first-in-class T cell engager directed against mUM2,*
- 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 cells2,10
- 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 synapse2
- 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 targeted2,10,13
* Based on in vitro and in vivo studies.2,10,13
Consider a blood test† for your patients with mUM to determine their HLA status and if KIMMTRAK is right for them2
† Provide a whole blood specimen to a CLIA-certified diagnostic lab and request a high-resolution HLA test.14,15
STUDY RESULTS
KIMMTRAK was proven to extend median overall survival (OS) by 6 months vs checkpoint inhibitors or chemotherapy in first-line2,7
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.
Primary end point: overall survival
43% of patients 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 progression16
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
Largest phase 3 clinical trial in mUM compared KIMMTRAK to checkpoint inhibitors or chemotherapy in first-line2
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.
Primary end point2
- Overall survival (OS)
Secondary end points2,18
- Progression-free survival (PFS)2
- Objective response rate (ORR)2
- Duration of response (DOR)18
- Disease control rate (DCR)18
- Stable disease (SD)18
NCCN category 1 preferred treatment option1,*
Tebentafusp-tebn (KIMMTRAK) is a category 1* preferred treatment option for HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma.1
This recommendation is based on the published phase 3 trial data, which evaluated tebentafusp-tebn overall survival benefit vs investigator's choice.†
* 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).
SAFETY
Low 3.3% discontinuation rate with KIMMTRAK2
KIMMTRAK adverse events were predictable and manageable† with 3.3% of patients discontinuing treatment due to adverse events (AEs)2,7
- In clinical trials, cytokine release syndrome (CRS), skin reactions, and elevated liver enzymes occurred following KIMMTRAK infusion.2 These events decreased in frequency and severity after the first 3 doses7
- 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 vomiting2
† 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
- 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.
Rash tended to occur early in treatment, decreased in incidence and severity, and was associated with 27-month median overall survival (mOS)2,7
- Severity and frequency of rash generally decreased following each of the first 3 infusions7
- 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 action2,7
- 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 benefit7
KIMMTRAK adverse events were generally predictable, manageable, and consistent with the proposed mechanism of action of KIMMTRAK2,7
- AEs tend to be on-target on-tumor (eg, CRS) or on-target off-tumor (eg, skin rashes), with decreasing frequency and intensity of treatment-related AEs over the first few doses2,7
- Most AEs occurred in the first few weeks7
- AEs were generally manageable with appropriate intervention2,7
- There was a low discontinuation rate for KIMMTRAK (3.3%) vs investigator’s choice (6.3%)2,16
CRS was observed following administration of KIMMTRAK2,7,16
- 89% of patients experienced any grade CRS2
- Cases were often mild and transient, with 0.8% grade 3-4 events and 1.2% discontinuations2
- In most cases of CRS, symptoms presented within the first 8 hours after infusion2
- Symptoms of CRS included fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, and headache2
- Fever was noted in nearly all cases of CRS16
- CRS events decreased in frequency and severity after the initial 3 doses7
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
- Most skin reactions were grade 1 (26%) or 2 (44%); some patients treated with KIMMTRAK experienced grade 3 reactions (21%). No grade 4 or 5 events were observed2
- Skin reactions included rash, pruritus, erythema, and cutaneous edema2
- Cases typically occurred following each of the first 3 KIMMTRAK infusions, with decreasing severity and frequency16
- The median time to onset of skin reactions was 1 day, with most resolved to ≤grade 1 between doses2
- There were no discontinuations of KIMMTRAK due to skin reactions,2 and 90% of patients' symptoms resolved without any systemic corticosteroids16
- No cases of Stevens-Johnson syndrome or toxic epidermal necrolysis were reported16
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
- 94% of patients in the study had preexisting liver metastasis2
- Most (73%) alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevations generally occurred within the first 3 KIMMTRAK infusions2
- Most patients experiencing grade 3 or 4 ALT/AST elevations had improvement to ≤grade 1 within 7 days with 0.4% discontinuations2
- More than 90% of patients were able to continue treatment beyond worst grade ALT/AST elevation16
- Elevations in bilirubin have been reported in 27% of patients2; these were primarily associated with increase in size of liver metastasis16
Monitor ALT, AST, and total blood bilirubin prior to the start of and during treatment with KIMMTRAK. Withhold KIMMTRAK according to severity.16
DOSING AND ADMINISTRATION
KIMMTRAK is administered once weekly via continuous IV infusion over 15‑20 minutes2
KIMMTRAK flat dosing is escalated over the first 3 doses, and KIMMTRAK is administered as a flat dose each time thereafter1
- If patient has not had a ≥grade 2 cytokine release syndrome adverse event with their previous dose.16
- If patient has not had hypotension requiring medical intervention with their most recent dose.2
- 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.
Monitoring for doses 1-3
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
Monitoring for doses 4+
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.
Treatment guide:
dosing and AE monitoring and management
DownloadPharmacist dosing,
preparation, and AE management guide
Pharmacist KIMMTRAK
preparation video
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:
A dedicated support system and educational resource
Coordination
of care
Financial and insurance assistance
Help with patient
and site of 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 status2
Patients must be HLA-A*02:01 positive to be eligible for KIMMTRAK. HLA-A*02:01 status can be determined by a simple blood test. The FDA-approved test for the detection of HLA-A*02:01 genotyping is the SeCore® HLA Sequencing System. Other HLA assays using whole blood that report to the fourth digit may be available at CLIA-certified laboratories. More 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. 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 November 9, 2021. Accessed January 13, 2022.