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HLA testing

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HLA-A*02:01-positive adult patients
with mUM are candidates for KIMMTRAK
1

Approximately 50% of adult patients with mUM are expected to be HLA-A*02:01 positive2

tube

Provide a whole blood specimen to your lab and request a high-resolution HLA test (ie, to the fourth digit)3,4

  • This test provides the necessary specificity, showing both the *02 and :01 portions
    • Low or intermediate resolution HLA testing only shows the *02 portion
  • Information on FDA-approved tests is available at www.fda.gov/companiondiagnostics1
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Do not use a biopsy tumor sample test for HLA5,6

  • Tumor chromosomal alterations may cause discrepancy in the results based on tumor heterogeneity

HLA-A*02:01 status does not change over a person’s life, and can be
tested/assessed at any time—so consider it early.7

Mechanism of action

A first-in-class T cell engager directed against mUM1

  • KIMMTRAK is an ImmTAC®* molecule that targets gp100, an intracellular antigen presented on the cells of HLA-A*02:01-positive patients with mUM1,8,9
  • KIMMTRAK binds to the gp100/HLA-A*02:01 complex to form an immune synapse, which activates cytotoxic T cells that target and kill gp100-expressing UM tumor cells1,8,10
    • Normal melanocytes could also be targeted10
  • KIMMTRAK has 1 million-fold greater affinity for gp100 presented by HLA-A*02:01 than natural T cell receptors8,11
  • T cell engager directed against mUM based on in vitro and in vivo studies1,10,12
  • *ImmTAC (Immune Mobilizing Monoclonal TCRs Against Cancer) molecules are bispecifics comprised of a T cell receptor targeting domain and an effector function pioneered by Immunocore.8

HLA-A, human leukocyte antigen-A; mUM, metastatic uveal melanoma; TCR, T cell receptor; UM, uveal melanoma.

Indication
 
Important Safety Information Including Boxed Warning

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.

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 ReactionsSkin 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 ToxicityKIMMTRAK 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.

References:
1. Kimmtrak. Package insert. Immunocore Ltd; 2022. 2. Marincola FM, Venzon D, White D, et al. HLA association with response and toxicity in melanoma patients treated with interleukin 2-based immunotherapy. Cancer Res. 1992;52(23):6561-6566. 3. Tiercy JM. How to select the best available related or unrelated donor of hematopoietic stem cells? Haematologica. 2016;101(6):680-687. doi:10.3324/haematol.2015.141119 4. Nunes E, Heslop H, Fernandez-Vina M, et al. Definitions of histocompatibility typing terms. Blood. 2011;118(23):e180-e183. doi:10.1182/blood-2011-05-353490 5. Fonseca C, Pinto-Proença R, Bergeron S, et al. Intratumoral heterogeneity in uveal melanoma. Ocul Oncol Pathol. 2021;7:17-25. https://doi.org/10.1159/000508517 6. Metzelaar-Blok JA, Jager MJ, Moghaddam PH, et al. Frequent loss of heterozygosity on chromosome 6p in uveal melanoma. Hum Immunol. 1999;60:962-969. 7. Choo SY. The HLA system: genetics, immunology, clinical testing, and clinical implications. Yonsei Med J. 2007;48(1):11-23. doi:10.3349/ymj.2007.48.1.11 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. Bakker AB, Schreurs MW, de Boer AJ, et al. Melanocyte lineage-specific antigen gp100 is recognized by melanoma-derived tumor-infiltrating lymphocytes. J Exp Med. 1994;179(3):1005-1009. doi:10.1084/jem.179.3.1005 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. 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 12. 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