Aetna Commercial Clinical Policy

Aetna Tebentafusp-tebn (Kimmtrak) Form

Effective Date

04/15/2022

Last Reviewed

05/04/2023

Original Document

  Reference



Background for this Policy

U.S. Food and Drug Administration (FDA)-Approved Indications

  • Kimmtrak is indicated for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma.

    • Tebentafusp-tebn is available as Kimmtrak (Immunocore Commercial LLC) and is a bispecific gp100 peptide-HLA directed T cell receptor (TCR) CD3 T cell engager. Tebentafusp-tebn is manufactured by recombinant DNA technology in

    Escherichia coli

    cells. The TCR arm attaches to a gp 100 peptide presented by human leukocyte antigen-A*02:01 (HLA-A*02:01) on the cell surface of uveal melanoma tumor cells. In vitro, tebentafusp-tebn binding to HLA-A*02:01-positive uveal melanoma cells and activation of polyclonal T cell release of inflammatory cytokines and cytolytic proteins resulted in uveal melanoma tumor cell lysis (Immunocore Commercial, 2022).

    Per the prescribing information, tebentafusp-tebn (Kimmtrak) carries the following warnings and precautions:

  • Cytokine release syndrome (CRS): CRS is a black box warning and may be life threatening in patients receiving Kimmtrak with manifestations that may include fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, and headache. In Study IMCgp100-202, CRS (≥ grade 2) was noted in 77% of patients receiving Kimmtrak.
  • Skin reactions: Patients have experienced rash (83%), pruritis (69%), erythema (25%), and cutaneous edema (27%) with Kimmtrak. In Study IMCgp100-202, skin reactions were noted in 91% of patients receiving Kimmtrak, including grade 2 (44%) and grade 3 (21%) events.
  • Elevated liver enzymes: Elevations in alanine aminotransferase or aspartate aminotransferase was noted in 65% of patients receiving Kimmtrak. Permanent discontinuation due to elevations in liver enzymes was noted in 0.4% of patients receiving Kimmtrak.
  • Embryo-fetal toxicity: Kimmtrak may cause fetal harm in a pregnant woman, and therefore, should be advised of potential risk. Females of reproductive potential should be advised to use effective contraception during Kimmtrak therapy and for 1 week after the last dose.

    • Per the prescribing information, Kimmtrak carries the following adverse reactions:

  • The most common adverse reactions (noted in ≥ 30%) included: cytokine release syndrome, rash, pyrexia, pruritis, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting.
  • The most common laboratory abnormalities (noted in ≥ 50%) included: decreased lymphocyte count, increased creatinine, increased glucose, increased aspartate aminotransferase, increased alanine aminotransferase, decreased hemoglobin, and decreased phosphate.

    • On January 25, 2022, the United States Food and Drug Administration (FDA) approved Kimmtrak (tebentafusp-tebn) for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma. The FDA granted priority review, breakthrough designation and orphan drug designation for Kimmtrak. The FDA approval was based on supporting data from the IMCgp100-202 study (FDA, 2022).

    Nathan and colleagues (2021) evaluated the efficacy of tebentafusp-tebn (Kimmtrak) for the treatment of patients with metastatic uveal melanoma in the IMCgp100-202 study, a randomized, open-label, multicenter, phase 3 trial. The patients in this trial were required to be previously untreated HLA-A*02:01-positive individuals with metastatic uveal melanoma. The patients (n=378) were stratified for lactate dehydrogenase level at study entry and randomization was performed in a 2:1 ratio for receiving tebentafusp-tebn (n=252 for tebentafusp-tebn group) or the investigator's choice of therapy with single-agent pembrolizumab, ipilimumab, or dacarbazine (n=126 for control group). The patients in the tebentafusp-tebn group received tebentafusp-tebn weekly by intravenous infusion administered at 20 mcg intravenously on day 1, 30 mcg intravenously on day 8, 68 mcg intravenously on day 15, and 68 mcg intravenously once every week thereafter. The primary study endpoint was overall survival. The results showed overall survival at 1 year as 73% in the tebentafusp-tebn group compared to 59% in the control group (hazard ratio for death, 0.51; 95% confidence interval [CI], 0.37 to 0.71; p<0.001) in the intention-to-treat population. Progression-free survival was significantly higher in the tebentafusp-tebn group compared to the control group (31% vs. 19% at 6 months; hazard ratio for disease progression or death, 0.73; 95% CI, 0.58 to 0.94; p=0.01). The most common treatment-related adverse events in the tebentafusp-tebn group included cytokine-mediated events and skin-related events. Patients experienced rash (83%), pyrexia (76%), and pruritis (69%). Discontinuation of trial treatment due to treatment-related adverse events was 2% and no treatment-related deaths were noted. The investigators concluded that tebentafusp-tebn therapy resulted in longer overall survival compared to control therapy for previously untreated patients with metastatic uveal melanoma.

    Uveal Melanoma

    Uveal melanoma is considered as an extremely rare type of cancer affecting the eye with an occurrence of about 5 cases per million in the United States. This type of cancer is diagnosed primarily at older ages, with an increase in incidence with age that peaks around an age of 70 years. In a majority of individuals, uveal melanoma develops in the uveal tract (iris, ciliary body, and choroid) of the eye. The uveal tract is the colored layer of tissue located under the white of the eye (sclera) and consists of normally pigmented cells and blood vessels. In choroidal or uveal melanoma, choroidal melanocytes (pigment producing cells in the eye) undergo transformation into cancerous cells. Symptomatic individuals with ocular melanoma may exhibit blurred vision, double vision, irritation, pain, a perception of flashes of light in the eye, a decrease in the total field of vision, and loss of vision. The risk of metastasis in uveal melanoma is dependent upon where along the uveal tract it develops. Iris melanomas have a low rate of metastasis compared to ciliary body and choroidal melanomas. It is estimated that 40-50% of individuals with uveal melanoma will develop metastatic disease. Metastasis from ciliary body or choroidal melanoma carries an associated 5-year mortality rate estimated at 30% compared with a rate of 2% to 3% for iris melanoma. The two primary therapeutic options for the treatment of uveal melanomas have been radiation therapy or surgery (NCI, 2021; NORD, 2022).

    Note

    : Requires Precertification:

    Precertification of tebentafusp-tebn (Kimmtrak) is required of all Aetna participating providers and members in applicable plan designs. For precertification of tebentafusp-tebn (Kimmtrak), call (866) 752-7021 (Commercial), or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see

    Specialty Pharmacy Precertification .

    For Medicare Part B plans, call (866) 503-0857, or fax (844) 268-7263.

    Criteria for Initial Approval

    Uveal Melanoma

    Aetna considers tebentafusp-tebn (Kimmtrak) medically necessary for treatment of uveal melanoma when

    all

    of the following criteria are met:

  • The member is HLA-A*02:01-positive;
    • and
  • The disease is unresectable or metastatic.

    • Aetna considers all other indications as experimental and investigational.

    Continuation of Therapy

    Aetna considers continuation of tebentafusp-tebn (Kimmtrak) therapy in members requesting reauthorization for an indication listed in Section I when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.