Tebentafusp-tebn (Kimmtrak)

Tebentafusp: teh-BEN-tah-fusp

Kimmtrak: KIM-trak

Kimmtrak can only be used to treat patients who test positive for HLA-A*02:01.

Advanced uveal melanoma

Kimmtrak is approved for:

• Patients with uveal melanoma (a type of eye cancer) that has spread to other parts of the body from the original cancer site, or cannot be removed by surgery.

Limitations of use

Age: The safety and efficacy of Kimmtrak in patients under 18 years of age have not been established.
Pregnancy/Breastfeeding: Kimmtrak may cause harm to a fetus, and is not recommended for use during pregnancy. Women should not start Kimmtrak treatment when pregnant and are advised to use contraception during treatment and for at least 1 week after the last dose of Kimmtrak. The risks associated with Kimmtrak during breastfeeding are not known and cannot be ruled out. Due to the potential for serious adverse reactions in the breastfed child, women are advised not to breastfeed during treatment and for 1 week after the last dose of Kimmtrak.

Antibody therapy

• Bispecific antibody therapy

Target:

• CD3 receptor on T cells
• gp100 peptide-HLA-A*02:01

Kimmtrak is a “bispecific protein” that was artificially made in the laboratory and can very precisely bind two different target molecules at the same time. Kimmtrak binds to:

• a molecule called CD3 on the surface of a T cell – the primary immune cell involved in killing cancer cells. CD3 is part of the T cell receptor, which is critical to the function of the T cell and is involved in stimulating the T cell to become active. 
• a complex of molecules called gp100 peptide–HLA-A*02:01 that is present on the surface of some cancer cells. gp100 is a molecule that is present in higher than normal amounts in cancer cells compared to healthy skin cells and is a tumor-associated antigen. Some cancer cells present gp100 on HLA-A02:01 molecules on their cell surface, and Kimmtrak can bind to this complex of molecules. 

Because Kimmtrak can bind to one molecule on cancer cells and another molecule on T cells at the same time, it acts as a bridge and brings the T cell in close contact with the cancer cell. By binding CD3 on the T cell, Kimmtrak also stimulates the T cell to become activated and kill the cancer cell it is bound to. Bispecific proteins that direct T cells to kill cancer cells by binding to both cells at the same time are known as T cell engagers.

Kimmtrak is administered weekly via a tube into a vein (intravenous infusion, or i.v.). During the first three infusions, the dose is slowly increased to the recommended dose. The first three infusions are administered over the course of 15-20 minutes in a hospital setting, and patients are observed for at least 16 hours after the administration of Kimmtrak for any symptoms related to the infusion. Subsequent infusions do not require a hospital stay, and patients are monitored for at least 30 min after the administration of Kimmtrak.

It is important to keep in mind that each patient’s outcome is individual and may be different from the results found in the clinical studies. In addition, immunotherapy can sometimes take several months to yield an observable treatment response.

Advanced uveal melanoma

In a clinical trial, 378 patients with uveal melanoma (a type of eye cancer) that had spread to other parts of the body from the original cancer site, or could not be removed by surgery, and who had not received prior treatment for their advanced disease, were either treated with Kimmtrak or the investigator’s choice of pembrolizumab (Keytruda), ipilimumab (Yervoy), or dacarbazine.

At a median follow-up of 14 months:

The most common side effects of Kimmtrak include skin reactions (dry skin, rash, itching, swelling), fever, tiredness, nausea, vomiting, chills, stomach pain, headache, low blood pressure, and abnormal liver blood tests. Some side effects, such as cytokine release syndrome, may be severe and life-threatening. Patients should report any symptoms to their healthcare provider, who can then initiate actions to limit or reverse the side effects.

Cytokine release syndrome (CRS)

CRS is caused by a widespread release of molecules called cytokines, which can cause inflammation and can affect the function of various organs. Cytokines may be released by the T cells to which Kimmtrak binds, or by other immune cells in the patient’s body. Signs and symptoms of CRS include fever, headache, nausea, low blood pressure, and weakness. A healthcare provider should be immediately notified if symptoms occur. CRS usually occurs at the beginning of the treatment, during the first three infusions.

For a more complete list of possible side effects, see the full prescribing information.

Manufacturer

Immunocore

Approval

FDA and EMA

Links to drug websites

• US: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761228s000lbl.pdf?utm_source=salesforce-marketing-cloud&utm_medium=email&utm_campaign=SPGA+-+FDA+Alert+-+01.26.2022&utm_term=View+full+prescribing+information+for+Kimmtrak
• Europe: https://www.ema.europa.eu/en/medicines/human/EPAR/kimmtrak

Other references

• Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. Nathan P, et al. The New England Journal of Medicine (2021)

Last updated on January 31, 2022

Tebentafusp: teh-BEN-tah-fusp

Kimmtrak: KIM-trak

Kimmtrak can only be used to treat patients who test positive for HLA-A*02:01.

Advanced uveal melanoma

Kimmtrak is approved for:

• Patients with uveal melanoma (a type of eye cancer) that cannot be removed by surgery, or has spread to other parts of the body from the original cancer site. 

Limitations of use

Limitations: Kimmtrak should only be administered in a qualified treatment center and by adequately trained healthcare professionals that can ensure proper monitoring and management of side effects associated with Kimmtrak.
Age: The safety and efficacy of Kimmtrak in patients under 18 years of age have not been established.
Pregnancy/Breastfeeding: Kimmtrak may cause harm to a fetus, and is not recommended for use during pregnancy. Patients should not start Kimmtrak treatment when pregnant and are advised to use contraception during treatment and for at least 1 week after the last dose of Kimmtrak. The risks associated with Kimmtrak during breastfeeding are not known and cannot be ruled out. Due to the potential for serious adverse reactions in the breastfed child, patients are advised not to breastfeed during Kimmtrak treatment.

Antibody therapy

• Bispecific antibody therapy

Target:

• CD3 receptor on T cells
• gp100 peptide-HLA-A*02:01

Kimmtrak is a “bispecific protein” that was artificially made in the laboratory and can very precisely bind two different target molecules at the same time. Kimmtrak binds to:

• a molecule called CD3 on the surface of a T cell – the primary immune cell involved in killing cancer cells. CD3 is part of the T cell receptor, which is critical to the function of the T cell and is involved in stimulating the T cell to become active. 
• a complex of molecules called gp100 peptide–HLA-A*02:01 that is present on the surface of some cancer cells. gp100 is a molecule that is present in higher than normal amounts in cancer cells compared to healthy skin cells and is a tumor-associated antigen. Some cancer cells present gp100 on HLA-A02:01 molecules on their cell surface, and Kimmtrak can bind to this complex of molecules. 

Because Kimmtrak can bind to one molecule on cancer cells and another molecule on T cells at the same time, it acts as a bridge and brings the T cell in close contact with the cancer cell. By binding CD3 on the T cell, Kimmtrak also stimulates the T cell to become activated and kill the cancer cell it is bound to. Bispecific proteins that direct T cells to kill cancer cells by binding to both cells at the same time are known as T cell engagers.

Kimmtrak is administered weekly via a tube into a vein (intravenous infusion, or i.v.). During the first three infusions, the dose is slowly increased to the recommended dose. The first three infusions are administered over the course of 15-20 minutes in a hospital setting, and patients are observed for at least 16 hours after the administration of Kimmtrak for any symptoms related to the infusion. Subsequent infusions do not require a hospital stay, and patients are monitored for at least 30 to 60 min after the administration of Kimmtrak.

It is important to keep in mind that each patient’s outcome is individual and may be different from the results found in the clinical studies. In addition, immunotherapy can sometimes take several months to yield an observable treatment response.

Advanced uveal melanoma

In a clinical trial, 378 patients with uveal melanoma (a type of eye cancer) that had spread to other parts of the body from the original cancer site, or could not be removed by surgery, and who had not received prior treatment for their advanced disease, were either treated with Kimmtrak or the investigator’s choice of pembrolizumab (Keytruda), ipilimumab (Yervoy), or dacarbazine.

At a median follow-up of 14 months:

The most common side effects of Kimmtrak include skin reactions (dry skin, rash, itching, swelling, changes in skin pigmentation), fever, tiredness, nausea, vomiting, chills, stomach pain, headache, low blood pressure, and abnormal liver blood tests. Some side effects, such as cytokine release syndrome, may be severe and life-threatening. Patients should report any symptoms to their healthcare provider, who can then initiate actions to limit or reverse the side effects.

Cytokine release syndrome (CRS)

CRS is caused by a widespread release of molecules called cytokines, which can cause inflammation and can affect the function of various organs. Cytokines may be released by the T cells to which Kimmtrak binds, or by other immune cells in the patient’s body. Signs and symptoms of CRS include fever, headache, nausea, low blood pressure, and weakness. A healthcare provider should be immediately notified if symptoms occur. CRS usually occurs at the beginning of the treatment, during the first three infusions.

For a more complete list of possible side effects, see the full prescribing information.

Manufacturer

Immunocore

Approval

FDA and EMA

Links to drug websites

• US: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761228s000lbl.pdf?utm_source=salesforce-marketing-cloud&utm_medium=email&utm_campaign=SPGA+-+FDA+Alert+-+01.26.2022&utm_term=View+full+prescribing+information+for+Kimmtrak
• Europe: https://www.ema.europa.eu/en/medicines/human/EPAR/kimmtrak

Other references

• Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. Nathan P, et al. The New England Journal of Medicine (2021)

Last updated on November 26, 2022