6-month improvement in median overall survival in metastatic uveal melanoma (mUM) in first-line

vs investigator's choice of pembrolizumab, ipilimumab, or dacarbazine1

NOW APPROVED

KIMMTRAK® (tebentafusp-tebn) is the first and only FDA-approved drug for metastatic uveal melanoma (mUM).

See the study

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Historically, there have been no FDA-approved treatments indicated for mUM‍—‍until now

Patients have faced a dismal prognosis, with a post-diagnosis median survival of approximately 9-16 months.2-5 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) have recommended enrollment in an investigational clinical trial, if appropriate, as a preferred option.6

Mechanism of Action Icon

MECHANISM OF ACTION

Proposed mechanism of action1,7

KIMMTRAK is a first-in-class T cell engager directed against mUM1,*

  • 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 tumor cells1,7
  • KIMMTRAK has 1 million–fold greater affinity for gp100 presented by HLA-A*02:01 than natural T cell receptors8,9
  • KIMMTRAK binds to uveal melanoma cells and cytotoxic T cells, forming an immune synapse1
  • 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 targeted1,7

* Based on in vitro and in vivo studies.

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STUDY RESULTS

KIMMTRAK was proven to extend median overall survival (OS) by 6 months vs checkpoint inhibitors or chemotherapy in first-line1,10

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

Overall Survival Graph

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 progression11

In clinical trials, patients stopped treatment for disease progression,* unless they were otherwise deriving benefit, or for unacceptable toxicity.1

* Two scans were required to confirm progression.11 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.12

Largest phase 3 clinical trial in mUM compared KIMMTRAK to checkpoint inhibitors or chemotherapy in first-line1

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.1,10,13

Metastatic Uveal Melanoma Phase 3 Chart

HLA-A, human leukocyte antigen-A; LDH, lactate dehydrogenase; ULN, upper limit of normal.

Radiologic assessment every 12 weeks.

Primary end point1

  • Overall survival (OS)

Secondary end points1,13

  • Progression-free survival (PFS)1
  • Objective response rate (ORR)1
  • Duration of response (DOR)13
  • Disease control rate (DCR)13
  • Stable disease (SD)13
Safety Icon

SAFETY

Low 3.3% discontinuation rate with KIMMTRAK1

KIMMTRAK adverse events were predictable and manageable† with 3.3% of patients discontinuing treatment due to adverse events (AEs)1,10

  • In clinical trials, cytokine release syndrome (CRS), skin reactions, and elevated liver enzymes occurred following KIMMTRAK infusion.1 These events decreased in frequency and severity after the first 3 doses10
  • 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 vomiting1

CRS symptoms were generally reversible and managed with IV fluids, NSAIDs, a single dose of corticosteroids, oxygen, and rarely, a vasopressor.1,10 Monitor fluid status, vital signs, and oxygenation level and provide appropriate therapy.1

Incidence of treatment-related AEs by week during treatment with KIMMTRAK10

AE Bar Chart

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) = 227.10

CRS represents algorithmic identification of cases based on ASTCT grading criteria (Lee at al. 2019). Rash represents a composite of multiple related terms.1

Adverse reactions occurring in ≥20% of patients receiving KIMMTRAK in study IMCgp100-2021

Adverse Reactions Kimmtrak Table
  1. Represents algorithmic identification of CRS cases based on ASTCT grading criteria (Lee et al. 2019).
  2. 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)1,10

  • Severity and frequency of rash generally decreased following each of the first 3 infusions10
  • 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 action1,10
Median Overall Survival
  • 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 benefit10

KIMMTRAK adverse events were generally predictable, manageable, and consistent with the proposed mechanism of action of KIMMTRAK1,10

  • 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 doses1,10
  • Most AEs occurred in the first few weeks10
  • AEs were generally manageable with appropriate intervention1,10
  • There was a low discontinuation rate for KIMMTRAK (3.3%) vs investigator’s choice (6.3%)1,11

CRS was observed following administration of KIMMTRAK1,10,11

  • 89% of patients experienced any grade CRS1
  • Cases were often mild and transient, with 0.8% grade 3-4 events and 1.2% discontinuations1
  • In most cases of CRS, symptoms presented within the first 8 hours after infusion1
  • Symptoms of CRS included fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, and headache1
  • Fever was noted in nearly all cases of CRS11
  • CRS events decreased in frequency and severity after the initial 3 doses10

CRS symptoms were generally reversible and managed with IV fluids, NSAIDs, a single dose of corticosteroids, oxygen, and rarely, a vasopressor.1,10 Monitor fluid status, vital signs, and oxygenation level and provide appropriate therapy.1

Skin reactions occurred in 91% of patients treated with KIMMTRAK1

  • 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 observed1
  • Skin reactions included rash, pruritus, erythema, and cutaneous edema1
  • Cases typically occurred following each of the first 3 KIMMTRAK infusions, with decreasing severity and frequency11
  • The median time to onset of skin reactions was 1 day, with most resolved to ≤grade 1 between doses1
  • There were no discontinuations of KIMMTRAK due to skin reactions,1 and 90% of patients' symptoms resolved without any systemic corticosteroids11
  • No cases of Stevens-Johnson syndrome or toxic epidermal necrolysis were reported11

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.1

Liver enzyme elevations were seen in 65% of patients treated with KIMMTRAK, with approximately 22% being grade 3‍-‍41

  • 94% of patients in the study had preexisting liver metastasis1
  • Most (73%) alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevations generally occurred within the first 3 KIMMTRAK infusions1
  • Most patients experiencing grade 3 or 4 ALT/AST elevations had improvement to ≤grade 1 within 7 days with 0.4% discontinuations1
  • More than 90% of patients were able to continue treatment beyond worst grade ALT/AST elevation11
  • Elevations in bilirubin have been reported in 27% of patients1; these were primarily associated with increase in size of liver metastasis11

Monitor ALT, AST, and total blood bilirubin prior to the start of and during treatment with KIMMTRAK. Withhold KIMMTRAK according to severity.11

Dosing and Administration Icon

DOSING AND ADMINISTRATION

KIMMTRAK is administered once weekly via continuous IV infusion over 15‑20 minutes1

KIMMTRAK flat dosing is escalated over the first 3 doses, and KIMMTRAK is administered as a flat dose each time thereafter1

Dosing Schedule Chart
  1. If patient has not had a ≥grade 2 cytokine release syndrome adverse event with their previous dose.11
  2. If patient has not had hypotension requiring medical intervention with their most recent dose.1
  3. 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.1

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).1

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

Pharmacist dosing,
preparation, and AE management guide

Pharmacist KIMMTRAK
preparation video

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SUPPORT

KIMMTRAK CONNECT logo

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.

KIMMTRAK CONNECT provides:

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A dedicated support system and educational resource

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Coordination
of care

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Financial and insurance assistance

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Help with patient
and site of care
coordination

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GETTING KIMMTRAK

How to get KIMMTRAK for your patients

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Verify HLA-A*02:01 status

Patients must be HLA-A*02:01 positive to be eligible for KIMMTRAK.1 HLA-A*02:01 status can be determined by a simple blood test. An FDA-approved test for the detection of HLA-A*02:01 genotyping is not currently available. The SeCore® HLA Sequencing System was used in the KIMMTRAK clinical trials,11 but there are multiple assays available from other diagnostic laboratories. Download the HLA fact sheet to learn more about testing your patients.

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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.

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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.

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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. Kimmtrak. Package insert. Immunocore Ltd; 2022. 2. 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 3. 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 4. 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 5. Rantala ES, Hernberg 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 6. National Comprehensive Cancer Network, Inc. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Melanoma: Uveal. Version 2.2021. National Comprehensive Cancer Network, Inc, website. NCCN.org. Published June 25, 2021. Accessed October 19, 2021. 7. 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 8. 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 9. 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 10. 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 11. Data on file. Immunocore. 12. 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 13. 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.