Tebentafusp-tebn is a CD3 T-cell engager that binds to gp100 expressed on the surface of melanoma cells and to CD3 expressed on the surface of T cells. It is indicated for the treatment of adults with HLA-A*02:01-positive unresectable or metastatic uveal melanoma. Tebentafusp has a black box warning for cytokine release syndrome; other serious adverse events include severe skin reactions and hepatotoxicity.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Tebentafusp is available as a single-dose 100 mcg/0.5 mL vial; further dilution is necessary prior to IV infusion.
-Add albumin to prevent adsorption of tebentafusp to the infusion bag and other components of the drug delivery system.
Preparation:
-Using a 1-mL syringe with a sterile needle, withdraw 0.5 mL of albumin 5% (50 g/L), 0.13 mL of albumin 20% (200 g/L), or 0.1 mL of albumin 25% (250 g/L) and add to a 100-mL 0.9% Sodium Chloride injection bag made of polyolefins (PO), such as polyethylene (PE) and polypropylene (PP), or polyvinyl chloride (PVC) for a final albumin concentration of 250 mcg/mL.
-Gently mix by inverting the infusion bag so that the bag is upside down with the entry port positioned on top and tap the side of the port tubing to ensure that any residual solution is released into the bulk solution.
-Continue mixing by gently rotating the bag lengthwise 360 degrees from the inverted position at least 5 times; do not shake the infusion bag.
-Repeat the inversion and rotation steps 3 additional times.
Drug Dilution:
-Do not shake the tebentafusp vial.
-Using a 1-mL syringe with a sterile needle, withdraw the appropriate volume from the tebentafusp 100 mcg/0.5 mL vial and add to the prepared infusion bag containing 0.9% Sodium Chloride injection and albumin.
20-mcg dose: Add 0.1 mL
30-mcg dose: Add 0.15 mL
68-mcg dose: Add 0.34 mL
-Repeat the inversion and rotation steps as specified in the Preparation section above; discard any unused portion of the vial.
-Storage of diluted admixture: Use immediately if possible. May be stored for up to 4 hours at room temperature or up to 24 hours in the refrigerator (2 to 8 degrees C; 36 to 46 degrees F); storage time includes from the time of preparation through the duration of the infusion.
-Once removed from the refrigerator, do not refrigerate the admixture again; do not freeze.
Intravenous (IV) Infusion:
-Allow the admixture solution to warm to room temperature if stored in the refrigerator.
-Administer the admixture solution as an IV infusion over 15 to 20 minutes using a dedicated IV line and a sterile, non-pyrogenic, low protein binding 0.2-micron in-line filter infusion set.
-After the infusion, flush the line with an adequate volume of sterile 0.9% Sodium Chloride injection to ensure that the entire contents of the infusion bag are given.
-Do not mix tebentafusp with other drugs or administer other drugs through the same IV line.
-Monitor patients during the infusion and for at least 16 hours after the infusion is complete for the first 3 doses. In patients who do not experience grade 2 or worse hypotension (requiring medical intervention) during or after the third infusion, continue subsequent infusions in an ambulatory setting and monitor for at least 30 minutes after each dose.
Skin reactions have been reported in 91% (grade 3, 21%) of patients who received tebentafusp in a clinical trial. Monitor patients for skin reactions including serious rash. Therapy interruption or discontinuation may be necessary in patients who develop grade 2 or higher skin toxicity. Treat with antihistamines and topical or systemic steroids based on persistence and severity of symptoms. Rash (83%; grade 3 or 4, 18%), pruritus (69%; grade 3 or 4, 4.5%), xerosis (31%), skin hypopigmentation (28%), cutaneous edema (27%), erythema (25%), hair discoloration/color changes (20%), flushing (less than 20%), alopecia (less than 20%), and skin hyperpigmentation (less than 20%) occurred in patients with HLA-A*02:01-positive advanced uveal melanoma who received tebentafusp (n = 245) in a randomized clinical trial. The median time to onset of skin reactions was 1 day (range, 1 to 55 days) and the median time to improvement to grade 1 or less was about 6 days.
Decreased lymphocyte count/lymphopenia (91%; grade 3 or 4, 56%), decreased hemoglobin level/anemia (51%; grade 3 or 4, 0.8%), decreased platelet count/thrombocytopenia (16%), and decreased neutrophil count/neutropenia (14%; grade 3 or 4, 2%) occurred in patients with HLA-A*02:01-positive advanced uveal melanoma who received tebentafusp (n = 245) in a randomized clinical trial.
Nausea (49%; grade 3 or 4, 2%), abdominal pain (45%; grade 3 or 4, 2.9%), vomiting (30%; grade 3 or 4, 1.2%), diarrhea (25%; grade 3 or 4, 1.2%), decreased appetite/anorexia (less than 20%), and constipation (less than 20%) occurred in patients with HLA-A*02:01-positive advanced uveal melanoma who received tebentafusp (n = 245) in a randomized clinical trial.
Nephrotoxicity, specifically increased creatinine level, occurred in 87% (grade 3 or 4, 0.4%) of patients with HLA-A*02:01-positive advanced uveal melanoma who received tebentafusp (n = 245) in a randomized clinical trial.
Hyperglycemia (66%; grade 3 or 4, 3.3%) and hypoglycemia (18%; grade 3 or 4, 0.4%) occurred in patients with HLA-A*02:01-positive advanced uveal melanoma who received tebentafusp (n = 245) in a randomized clinical trial.
Hypoalbuminemia occurred in 47% (grade 3 or 4, 2.1%) of patients with HLA-A*02:01-positive advanced uveal melanoma who received tebentafusp (n = 245) in a randomized clinical trial.
Fever (76%; grade 3 or 4, 3.7%) and chills (48%; grade 3 or 4, 0.4%) occurred in patients with HLA-A*02:01-positive advanced uveal melanoma who received tebentafusp (n = 245) in a randomized clinical trial.
Hypophosphatemia (51%; grade 3 or 4, 11%), hypocalcemia (45%; grade 3 or 4, 1.6%), hypomagnesemia (34%), hyponatremia (30%; grade 3 or 4, 2.9%), hyperkalemia (29%; grade 3 or 4, 1.6%), hypokalemia (17%; grade 3 or 4, 0.8%) and hypercalcemia (13%) occurred in patients with HLA-A*02:01-positive advanced uveal melanoma who received tebentafusp (n = 245) in a randomized clinical trial.
Increased lipase level (37%; grade 3 or 4, 15%) and hyperamylasemia (23%; grade 3 or 4, 4.1%) occurred in patients with HLA-A*02:01-positive advanced uveal melanoma who received tebentafusp (n = 245) in a randomized clinical trial.
Fatigue occurred in 64% (grade 3 or 4, 6%) of patients with HLA-A*02:01-positive advanced uveal melanoma who received tebentafusp (n = 245) in a randomized clinical trial.
Edema occurred in 45% of patients with HLA-A*02:01-positive advanced uveal melanoma who received tebentafusp (n = 245) in a randomized clinical trial.
Night sweats occurred in less than 20% of patients with HLA-A*02:01-positive advanced uveal melanoma who received tebentafusp (n = 245) in a randomized clinical trial.
Dyspnea occurred in less than 20% of patients with HLA-A*02:01-positive advanced uveal melanoma who received tebentafusp (n = 245) in a randomized clinical trial.
Headache (31%; grade 3 or 4, 0.4%), paresthesias (less than 20%), and dizziness (less than 20%) occurred in patients with HLA-A*02:01-positive advanced uveal melanoma who received tebentafusp (n = 245) in a randomized clinical trial.
Arthralgia (22%; grade 3 or 4, 0.8%), back pain (less than 20%), muscle cramps/spasms (less than 20%), myalgia (less than 20%), and pain in extremity (less than 20%) occurred in patients with HLA-A*02:01-positive advanced uveal melanoma who received tebentafusp (n = 245) in a randomized clinical trial.
Hypotension (39%; grade 3 or 4, 3.3%), tachycardia/sinus tachycardia (less than 20%), and hypertension (less than 20%) occurred in patients with HLA-A*02:01-positive advanced uveal melanoma who received tebentafusp (n = 245) in a randomized clinical trial.
Influenza-like illness and oropharyngeal pain each occurred in less than 20% of patients with HLA-A*02:01-positive advanced uveal melanoma who received tebentafusp (n = 245) in a randomized clinical trial.
Fatal pulmonary embolism was reported in 1 patient (0.4%) with HLA-A*02:01-positive advanced uveal melanoma who received tebentafusp (n = 245) in a randomized clinical trial.
Cytokine release syndrome (CRS) has been reported in 89% (grade 3 or 4, 0.8%) of patients with HLA-A*02:01-positive advanced uveal melanoma who received tebentafusp (n = 245) in a randomized clinical trial. Some cases of CRS were serious or life-threatening. Symptoms may include fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminase levels, fatigue, and headache. Closely monitor patients (e.g., fluid status, vital signs, and oxygenation level) for signs or symptoms of CRS for 16 hours after the completion of the infusion; initiate appropriate therapy/supportive care as required. In patients who do not experience grade 2 or greater hypotension (requiring medical intervention) during or after the third infusion, subsequent infusions may be given in an ambulatory setting; monitor patients for at least 30 minutes after the end of each infusion. Therapy interruption or discontinuation may be necessary in patients who develop CRS. In patients who develop 2 to 3 hours of moderate CRS or severe CRS, premedicate with dexamethasone (4 mg or equivalent) at least 30 minutes prior to the next dose. Administer IV corticosteroids (e.g., 2 mg/kg per day methylprednisolone or equivalent) in patients who develop severe or life-threatening CRS. In the clinical trial, 60% of patients experienced grade 2 or higher CRS with more than 1 tebentafusp infusion. The median number of CRS episodes was 2 (range, 1 to 12). Most (84%) of the CRS events started the day of infusion and the median time to resolution was 2 days in cases that resolved. Additionally, 23% of patients received systemic corticosteroids for at least 1 infusion, 8% of patients received supplemental oxygen during at least 1 infusion, and 0.8% of patients received a vasopressor for at least 1 infusion.
Elevated hepatic enzymes were reported in 65% of patients who received tebentafusp in a clinical trial. Most cases of elevated hepatic enzymes occurred within the first 3 infusions; some cases occurred concurrently with cytokine release syndrome (CRS). Monitor liver function tests including total bilirubin level prior to and during tebentafusp therapy. Therapy interruption or discontinuation may be necessary in patients who develop grade 3 or 4 hepatotoxicity. Increased ALT (52%; grade 3 or 4, 9%), AST (55%; grade 3 or 4, 13%), and alkaline phosphatase (34%; grade 3 or 4, 2.9%) levels and hyperbilirubinemia (27%; grade 3 or 4, 4.1%) occurred in patients with HLA-A*02:01-positive advanced uveal melanoma who received tebentafusp (n = 245) in a randomized clinical trial. Most transaminase level elevations (73%) occurred within the first 3 tebentafusp infusions; severe elevations typically improved to grade 1 or less within 7 days. In patient who developed increased ALT/AST levels without concurrent CRS, the median time to onset was 129 days and about 8% of patients experienced grade 3 or 4 transaminase level elevations.
Antibody formation to tebentafusp were detected in 33% and 29% of patients in 2 clinical studies. These treatment-emergent anti-drug antibodies occurred at a median onset time of 6 to 9 weeks after the start of therapy. In an exploratory analysis, antibody formation did not have a clinically significant impact on overall survival or the frequency or severity of hypersensitivity reactions.
Cerebral edema that led to permanent therapy discontinuation was reported in 1 patient (0.4%) with HLA-A*02:01-positive advanced uveal melanoma who received tebentafusp (n = 245) in a randomized clinical trial.
Anaphylactoid reactions that led to permanent therapy discontinuation was reported in 1 patient (0.4%) with HLA-A*02:01-positive advanced uveal melanoma who received tebentafusp (n = 245) in a randomized clinical trial.
Cytokine release syndrome (CRS) has been reported in patients who received tebentafusp; some cases were serious or life-threatening. Symptoms may include fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminase levels, fatigue, and headache. Tebentafusp administration requires a specialized care setting where health care providers have immediate access to emergency medications and resuscitative equipment to manage CRS. Screen patients for dehydration prior to starting therapy. Closely monitor patients (e.g., fluid status, vital signs, and oxygenation level) for signs or symptoms of CRS for 16 hours after the completion of the infusion; initiate appropriate therapy as required. In patients who do not experience grade 2 or greater hypotension (requiring medical intervention) during or after the third infusion, subsequent infusions may be given in an ambulatory setting; monitor patients for at least 30 minutes after the end of each infusion. Therapy interruption or discontinuation may be necessary in patients who develop CRS. In patients who develop 2 to 3 hours of moderate CRS or severe CRS, premedicate with dexamethasone (4 mg or equivalent) at least 30 minutes prior to the next dose. Administer IV corticosteroids (e.g., 2 mg/kg per day methylprednisolone or equivalent) in patients who develop severe or life-threatening CRS.
Skin reactions have been reported in patients who received tebentafusp. Monitor patients for skin reactions including serious rash. Therapy interruption or discontinuation may be necessary in patients who develop grade 2 or higher skin toxicity. Treat skin toxicity with antihistamines and topical or systemic steroids based on persistence and severity of symptoms.
Hepatotoxicity (e.g., elevated hepatic enzymes, hyperbilirubinemia) has been reported in patients who received tebentafusp. Most cases occurred within the first 3 infusions; some cases occurred concurrently with cytokine release syndrome. Monitor liver function tests including total bilirubin level prior to and during tebentafusp therapy. Therapy interruption or discontinuation may be necessary in patients who develop grade 3 or 4 hepatotoxicity.
Tebentafusp may cause fetal harm if administered during pregnancy, based on its mechanism of action. Patients of reproductive potential should avoid pregnancy and use effective contraction during and after tebentafusp therapy. Advise pregnant patients of the potential risk to the fetus with tebentafusp use. It has not been studied in pregnant woman and no animal reproductive or developmental toxicity studies have been conducted. However, other drugs with similar molecular weight are known to cross the placenta resulting in fetal exposure.
Counsel patients about the reproductive risk and contraception requirements during tebentafusp treatment. Pregnancy testing should be performed prior to starting tebentafusp in patients of reproductive potential. These patients should use effective contraception during therapy and for 1 week after the last tebentafusp dose.
It is not known if tebentafusp is secreted in human milk or if it has effects on the breast-fed child or on milk production. Due to the potential for serious adverse reactions in a breastfed child, patients should avoid breast-feeding during therapy and for 1 week after the last tebentafusp dose.
For the treatment of uveal melanoma:
NOTE: The FDA has designated tebentafusp an orphan drug for this indication.
-for the treatment of HLA-A*02:01-positive unresectable or metastatic uveal melanoma:
NOTE: Select patients based on a positive HLA-A*02:01 genotyping test of a whole blood sample. Information on FDA-approved tests is available at http://www.fda.gov/companiondiagnostics.
Intravenous dosage:
Adults: 20 micrograms (mcg) IV on day 1, 30 mcg IV on day 8, 68 mcg IV on day 15, and then 68 mcg IV once weekly until disease progression. Therapy interruption or permanent discontinuation may be necessary in patients who develop severe toxicity. At a median follow-up time of 43.3 months, the median overall survival (OS) time was significantly improved with tebentafusp compared with investigator-choice therapy (21.6 months vs. 16.9 months; hazard ratio (HR) = 0.68; 95% CI, 0.54 to 0.87) in adult patients with previously untreated HLA-A*02:01-positive metastatic uveal melanoma in a randomized (2:1), phase 3 (IMCgp100-202) trial (n =378). The estimated 1-year OS rates were 73% and 60% in the tebentafusp and investigator-choice arms, respectively; the estimated 3-year OS rates were 27% and 18%, respectively. The median progression-free survival time was also significantly improved with tebentafusp compared with investigator-choice therapy (3.4 months vs. 2.9 months; HR = 0.76; 95% CI, 0.6 to 0.97). Of note, 16 patients in the investigator-choice arm crossed over to the tebentafusp arm after a favorable survival benefit was demonstrated with tebentafusp therapy in the first interim analysis. In this study, investigator-choice therapy consisted of single-agent pembrolizumab (n = 103), ipilimumab (n = 16), or dacarbazine (n = 7).
Therapeutic Drug Monitoring:
Management of Treatment-Related Toxicity
Cytokine Release Syndrome (CRS)
Moderate CRS defined as temperature of 38 degrees C or higher with either hypotension that responds to fluids (does not require vasopressors) or hypoxia requiring low flow nasal canula (6 L/min or less) or blow-by oxygen: If hypotension and/or hypoxia do not improve within 3 hours or CRS symptoms worsen, escalate care and manage according to next higher level of severity. In patients who experience 2 to 3 hours of moderate CRS, administer dexamethasone (4 mg or equivalent) premedication at least 30 minutes prior to the next dose.
Severe CRS defined as temperature of 38 degrees C or higher with either hemodynamic instability requiring a vasopressor (with or without vasopressin) or worsening hypoxia or respiratory distress requiring high flow nasal canula (more than 6 L/minute of oxygen) or face mask: Hold therapy until CRS and associated symptoms have resolved and start IV corticosteroids (e.g., 2 mg/kg per day methylprednisolone or equivalent). Resume tebentafusp at the same dose level; if the toxicity occurs with the initial dose escalation, do not escalate the dose until that dose is tolerated. Administer dexamethasone (4 mg or equivalent) premedication at least 30 minutes prior to the next dose.
Life-threatening CRS defined as temperature of 38 degrees C or higher with hemodynamic instability requiring multiple vasopressors (excluding vasopressin) and/or worsening hypoxia or respiratory distress despite oxygen administration requiring positive pressure: Permanently discontinue therapy and start IV corticosteroids (e.g., 2 mg/kg per day methylprednisolone or equivalent).
Skin Reactions
Grade 2 or 3 toxicity: Hold therapy until toxicity resolves to grade 1 or less or baseline. Resume tebentafusp at the same dose level; if grade 3 skin toxicity occurs with the initial dose escalation, do not escalate the dose until that dose is tolerated. Consider changing to an IV corticosteroid (e.g., 2 mg/kg per day methylprednisolone or equivalent) for persistent reactions not responding to oral steroids.
Grade 4 toxicity: Permanently discontinue therapy and start IV corticosteroids (e.g., 2 mg/kg per day methylprednisolone or equivalent).
Other Adverse Reactions
Grade 3 toxicity: Hold therapy until toxicity resolves to grade 1 or less or baseline. Resume tebentafusp at the same dose level; if grade 3 toxicity occurs with the initial dose escalation, do not escalate the dose until that dose is tolerated.
Grade 4 toxicity: Permanently discontinue therapy.
Maximum Dosage Limits:
-Adults
68 mcg IV.
-Geriatric
68 mcg IV.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Baseline hepatic impairment: Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Treatment-related grade 3 or 4 elevated hepatic enzymes: Hold therapy until toxicity resolves to grade 1 or less or baseline. Administer an IV corticosteroid if there is no improvement within 24 hours. If the toxicity occurred concurrently with grade 3 cytokine release syndrome (CRS), resume tebentafusp at the same dose level and resume dose escalation if the next administration is tolerated. If the toxicity occurred without grade 3 CRS, resume dose escalation if the dose is less than 68 mcg or resume at the same dose level if dose escalation has completed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Tebentafusp is a bispecific T-cell engager (BiTE) fusion protein that binds the gp100 peptide presented by human leukocyte antigen-A*02:01 (HLAA*02:01) on the cell surface of uveal melanoma tumor cells to CD3 expressed on the surface of T cells. Tebentafusp is a cancer immunotherapy that utilizes an immune-mobilizing monoclonal T-cell receptors against cancer (ImmTAC) platform. ImmTAC molecules work by binding to cells that present a peptide derived from a target antigen and then recruiting T cells to lyse the target. Tebentafusp binding enables polyclonal activation of native T cells to release inflammatory cytokines and cytolytic proteins resulting in direct lysis of uveal melanoma tumor cells. ImmTAC molecules may have an advantage over antibody-based therapeutics that target only highly expressed, cell surface proteins and immune checkpoint inhibitors which require preexisting cancer-specific T-cells to lyse cancer cells.
Tebentafusp is administered intravenously. It has a geometric mean steady-state volume of distribution of 7.56 L (coefficient of variation (CV), 24%), geometric mean clearance of 16.4 L/day (CV, 24.5%), and median terminal half-life of 7.5 hours (range, 6.8 to 7.5 hours). It is metabolized into small peptides and amino acids via catabolism.
Affected cytochrome P450 isoenzymes: CYP450 substrates
Although no drug interaction studies have been performed with tebentafusp, CYP450 enzyme activity may be suppressed due to an elevation of certain proinflammatory cytokines during therapy.
-Route-Specific Pharmacokinetics
Intravenous Route
The steady-state geometric mean Cmax and AUC(0-7d) values are 13 nanograms (ng)/mL (coefficient of variation (CV), 34.6%) and 4.6 ng X day/mL (CV, 23%), respectively, with no accumulation following the administration of the approved recommended tebentafusp dosage in patients with metastatic uveal melanoma. After a single dose of tebentafusp, the Cmax and AUC(0-7d) values increased in an approximate dose proportional manner over a dose range of 20 to 68 mg.
-Special Populations
Hepatic Impairment
Mild hepatic impairment (total bilirubin level up to the ULN and AST level greater than the ULN OR total bilirubin level of 1 to 1.5 times the ULN and any AST level) has no clinically significant impact on the pharmacokinetic (PK) parameters of tebentafusp. The effects of moderate to severe hepatic impairment (total bilirubin level greater than 1.5 times the ULN and any AST level) on the PK parameters of tebentafusp have not been evaluated.
Renal Impairment
Mild to moderate renal impairment (creatinine clearance (CrCl) of 30 to 89 mL/min) has no clinically significant impact on the pharmacokinetic (PK) parameters of tebentafusp. The effects of severe renal impairment (CrCl of less than 30 mL/min) on the PK parameters of tebentafusp have not been evaluated.
Geriatric
Age (range, 23 to 91 years) has no clinically significant impact on the pharmacokinetic parameters of tebentafusp.
Gender Differences
Sex has no clinically significant impact on the pharmacokinetic parameters of tebentafusp.
Obesity
Weight (range, 43 to 163 kg) has no clinically significant impact on the pharmacokinetic parameters of tebentafusp.
Other
Immunogenicity
The tebentafusp clearance was increased, exposure was decreased (by 97%), and the terminal half-life was decreased (to 10 to 14 minutes) in patients with high titer anti-drug antibodies.