Dosing & Uses
Dosage Forms & Strengths
injectable solution
- 100mcg/0.5mL (single-dose vial)
Uveal Melanoma
Indicated for treatment of HLA-A*02:01-positive adults with unresectable or metastatic uveal melanoma
Day 1: 20 mcg IV
Day 8: 30 mcg IV
Day 15 and weekly thereafter: 68 mcg IV
Continue until unacceptable toxicity or disease progression occurs
Dosage Modifications
Cytokine release syndrome (CRS)
-
Moderate
- Defined as temperature ≥38°C with hypotension that responds to fluids (does not require vasopressors) OR hypoxia requiring low-flow nasal canula (≤6 L/min) or blow-by oxygen
- If hypotension and hypoxia do not improve within 3 hr or CRS worsens, escalate care and manage according to next higher level of severity
- For persistent moderate (lasting 2-3 hr) or recurrent CRS, administer corticosteroid premedication (eg, dexamethasone 4 mg or equivalent) at least 30 minutes before next dose
-
Severe
- Defined as temperature ≥38°C with hemodynamic instability requiring a vasopressor (with or without vasopressin) OR worsening hypoxia or respiratory distress requiring high-flow nasal canula (>6 L/min oxygen) or face mask
- Withhold until CRS and sequelae resolves
- Administer IV corticosteroid (eg, 2 mg/kg/day methylprednisolone or equivalent)
- Resume at same dose level (ie, do not escalate if severe CRS occurred during initial dose escalation; resume escalation once dosage is tolerated)
- For severe CRS, administer corticosteroid premedication (eg, dexamethasone 4 mg or equivalent) at least 30 minutes before next dose
-
Life-threatening
- Defined as temperature ≥38°C with hemodynamic instability requiring multiple vasopressors (excluding vasopressin) OR worsening hypoxia or respiratory distress despite oxygen administration requiring positive pressure
- Permanently discontinue
- Administer IV corticosteroid (eg, 2 mg/kg/day methylprednisolone or equivalent)
Skin reactions
-
Grade 2 or 3
- Withhold until Grade ≤1 or baseline
- Resume at same dose level (ie, do not escalate if Grade 3 skin reactions occurred during initial dose escalation; resume escalation once dose is tolerated)
- For persistent reactions not responding to oral steroids, consider IV corticosteroid (eg, 2 mg/kg/day methylprednisolone or equivalent)
-
Grade 4
- Permanently discontinue
- Administer IV corticosteroid (eg, 2 mg/kg/day methylprednisolone or equivalent)
Elevated liver enzymes
-
Grade 3 or 4
- Withhold until Grade ≤1 or baseline
- Occurs in Grade 3 CRS setting: Resume at same dose level; resume escalation if next administration is tolerated
- Occurs outside Grade 3 CRS setting: Resume escalation if current dose <68 mcg, or resume at same dose level if dose escalation completed
- Administer IV corticosteroids if no improvement within 24 hr
Other adverse reactions
-
Grade 3
- Withhold until Grade ≤1 or baseline
- Resume at same dose level (ie, do not escalate if other Grade 3 adverse reaction occurred during initial dose escalation; resume escalation once dosage is tolerated)
-
Grade 4
- Permanently discontinue
Renal impairment
- Mild or moderate (CrCl 30-89 mL/min): No dosage adjustment necessary
- Severe (CrCl <30 mL/min): Not studied
Hepatic impairment
- Mild (total bilirubin [TB] ≤1.5x ULN and any AST): No dosage adjustment necessary
- Moderate or severe (TB ≤10x ULN and any AST): Not studied
Dosing Considerations
Verify pregnancy status in females of reproductive potential before initiating
Patient selection
- Select patients for unresectable or metastatic uveal melanoma based on positive HLA-A*02:01 genotyping test
- An FDA-approved test for detecting HLA-A*02:01 genotype is currently unavailable
Safety and efficacy not established
Adverse Effects
>10%
All grades
- Lymphocyte count decreased (91%)
- Cytokine release syndrome (CRS) (89%)
- Creatinine increased (87%)
- Rash (83%)
- Pyrexia (76%)
- Pruritus (69%)
- Glucose increased (66%)
- Fatigue (64%)
- AST increased (55%)
- ALT increased (52%)
- Hemoglobin decreased (51%)
- Phosphate decreased (51%)
- Nausea (49%)
- Chills (48%)
- Albumin decreased (47%)
- Abdominal pain (45%)
- Calcium decreased (45%)
- Edema (45%)
- Hypotension (39%)
- Lipase increased (37%)
- Magnesium decreased (34%)
- Alkaline phosphatase increased (34%)
- Dry skin (31%)
- Headache (31%)
- Vomiting (30%)
- Sodium decreased (30%)
- Potassium increased (29%)
- Skin hypopigmentation (28%)
- Bilirubin increased (27%)
- Diarrhea (25%)
- Erythema (24%)
- Amylase increased (23%)
- Arthralgia (22%)
- Hair color changes (20%)
- Glucose decreased (18%)
- Potassium decreased (17%)
- Platelet count decreased (16%)
- Neutrophil count decreased (14%)
- Calcium increased (13%)
Grade 3 or 4
- Lymphocyte count decreased (56%)
- Rash (18%)
- Lipase increased (15%)
- AST increased (13%)
- Phosphate decreased (11%)
1-10%
Grade 3 or 4
- ALT increased (9%)
- Fatigue (6%)
- Pruritus (4.5%)
- Bilirubin increased (4.1%)
- Amylase increased (4.1%)
- Pyrexia (3.7%)
- Hypotension (3.3%)
- Glucose increased (3.3%)
- Abdominal pain (2.9%)
- Sodium decreased (2.9%)
- Alkaline phosphatase increased (2.9%)
- Albumin decreased (2.1%)
- Nausea (2%)
- Neutrophil count decreased (2%)
- Potassium increased (1.6%)
- Calcium decreased (1.6%)
- Diarrhea (1.2%)
- Vomiting (1.2%)
<1%
Grade 3 or 4
- CRS (0.8%)
- Arthralgia (0.8%)
- Potassium decreased (0.8%)
- Hemoglobin decreased (0.8%)
- Chills (0.4%)
- Headache (0.4%)
- Creatinine increased (0.4%)
- Glucose decreased (0.4%)
Warnings
Black Box Warnings
Cytokine release syndrome (CRS)
- CRS, which may be serious or life-threatening, occurred
- Monitor for at least 16 hr following first 3 infusions and then as clinically indicated
Contraindications
None
Cautions
Increases in AST/ALT were observed; in majority of patients experiencing elevated ALT/AST, occurred within the first 3 infusions; monitor AST, ALT, and total blood bilirubin before initiating and during treatment; withhold according to severity
May cause fetal harm when administered to pregnant females
CRS
- CRS occurred
- May manifest as fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, and headache
- Ensure that healthcare providers have immediate access to medications and resuscitative equipment to manage CRS
- Ensure patients are euvolemic before initiating
- Closely monitor for signs or symptoms of CRS following infusions
- Monitor fluid status, vital signs, and oxygenation level and provide appropriate therapy
- Withhold or discontinue, depending on persistence and severity of CRS
Skin reactions
- Skin reactions (eg, rash, pruritus, cutaneous edema) reported
- Median time to onset was 1 day; median time to improvement to Grade ≤1 was ~6 days
- Monitor 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, depending on severity of skin reactions
Drug interaction overview
- Elevation of certain proinflammatory cytokines may suppress CYP450 enzyme activities
Pregnancy & Lactation
Pregnancy
Based on mechanism of action, fetal harm may occur when administered to pregnant females
No data are available data on pregnant females
Molecules of similar molecular weight can cross the placenta, resulting in fetal exposure; advise females of potential risks to fetus
Verify pregnancy status in females of reproductive potential before initiating
Contraception
- Females of reproductive potential: Use effective contraception during treatment and for 1 week following last dose
Animal data
- No animal reproductive and developmental toxicity studies have been conducted
Lactation
No data are available on presence of tebentafusp in human milk, effects on breastfed infants, or effects on milk production
Advise patients not to breastfeed during treatment and for at least 1 week after last dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Bispecific protein comprised of a soluble T-cell receptor fused to an anti-CD3 immune-effector function that specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma
Immune-mobilizing monoclonal T-cell receptors (TCRs) against cancer (ImmTAC) molecules bind cells that present a peptide derived from an antigen of interest, and recruit T-cells to lyse the target cells; to achieve this, ImmTAC molecules are composed of a TCR targeting domain and a single-chain variable fragment (scFv) anti-CD3 effector domain
The TCR targeting domain binds peptides presented on the cell surface as a human leukocyte antigen (HLA)–peptide (pHLA) complex, while the anti-CD3 effector domain engages and activates CD3+ cells
Absorption
Peak plasma concentration: 13 ng/mL
AUC: 4.6 ng·day/mL
Distribution
Vd (steady-state): 7.56 L
Metabolism
Expected to be catabolized into small peptides and amino acids
Elimination
Clearance: 16.4 L/day
Half-life: 7.5 hr
Administration
IV Incompatibilities
Do not mix with other drugs or administer other drugs through same IV line
IV Compatibilities
Infusion bag: 0.9% NaCl and albumin (human)
Prepared IV bag for infusion: 0.9% NaCl
IV Preparation
Requires 2-step dilution process for preparing final dose for infusion
Visually inspect vials and infusion bags for particulate matter and discoloration before administering
Prepare infusion bag
- Using a 1-mL syringe with graduations of 2 decimal places and a sterile needle, withdraw calculated volume (listed below) of albumin (human) into syringe
- 5% (50 g/L) concentration: 0.5 mL
- 20% (200 g/L) concentration: 0.13 mL
- 25% (250 g/L): 0.1 mL
- Add albumin to 100-mL 0.9% NaCl bag constructed of polyolefins (PO) (eg, polyethylene [PE] and polypropylene [PP]) or polyvinyl chloride (PVC) to make a final 250 mcg/mL albumin concentration
-
Gently homogenize prepared solution by completing the following
- Invert infusion bag so that bag is upside-down, with entry port positioned on top; then tap side of port tubing to ensure the release of any residual solution
- Mix prepared solution by gently rotating bag lengthwise 360º from inverted position ≥5 times; do not shake infusion bag
- Repeat these steps an additional 3 times
Dilute tebentafusp solution before administration
- Do not shake vial
- Using a 1-mL syringe with graduations of 2 decimal places and a sterile needle, withdraw required drug volume and add to prepared 100-mL infusion bag containing 0.9% NaCl plus albumin
-
Dose and drug volume to add to prepared infusion bag
- Day 1: 20 mcg (0.1 mL)
- Day 8: 30 mcg (0.15 mL)
- Day 15 and weekly thereafter: 68 mcg (0.34 mL)
- Discard any unused portion in accordance with local requirements; do not prepare more than 1 dose from vial
-
Gently homogenize prepared solution by completing the following
- Invert infusion bag so that bag is upside-down, with entry port positioned on top; then tap side of port tubing to ensure the release of any residual solution
- Mix prepared solution by gently rotating bag lengthwise 360º from inverted position ≥5 times; do not shake infusion bag
- Repeat these steps an additional 3 times
IV Administration
Administer IV infusion immediately following preparation
Infuse over 15-20 minutes through a dedicated IV line; use sterile, nonpyrogenic, low–protein binding 0.2–micron inline filter infusion set
Administer entire contents of infusion bag within 4 hr from time of preparation including duration of infusion
Do not mix with other drugs or administer other drugs through same IV line
Once infusion completed, flush infusion line with sterile 0.9% NaCl to ensure that entire contents of infusion bag are administered
Administer first 3 infusions in an appropriate healthcare setting; observe patient for at least 16 hr following the first 3 infusions and for at least 30 minutes after future infusions
If patient does not experience Grade 2 or worse hypotension (requiring medical intervention) during or after third infusion, administer subsequent doses in an appropriate ambulatory-care setting, and monitor patients for a minimum of 30 minutes after infusion
Storage
Unopened vials
- Protect from light
- Refrigerate at 2-8ºC (36-46ºF)
- Do not freeze; do not shake
Diluted infusion bag for administration
- Use immediately
- Administer within 4 hr from time of preparation including duration of infusion; during 4-hr window, store infusion bag at room temperature
- If not used immediately, refrigerate at 2-8ºC (36-46ºF) and infuse within 24 hr from time of preparation, which includes storage time in refrigerator, recalibration to room temperature, and duration of infusion
- Once removed from refrigerator, do not refrigerate infusion bag again; do not freeze
- Discard unused solution beyond recommended storage time
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Formulary
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