tebentafusp (Rx)

Brand and Other Names:Kimmtrak, tebentafusp-tebn
  • Print

Dosing & Uses

AdultPediatric

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

Next:

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%)
Previous
Next:

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

Previous
Next:

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.

Previous
Next:

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

Previous
Next:

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
Previous
Next:

Images

No images available for this drug.
Previous
Next:

Patient Handout

A Patient Handout is not currently available for this monograph.
Previous
Next:

Formulary

FormularyPatient Discounts

Adding plans allows you to compare formulary status to other drugs in the same class.

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
  • Manage and view all your plans together – even plans in different states.
  • Compare formulary status to other drugs in the same class.
  • Access your plan list on any device – mobile or desktop.

The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
Additional Offers
Email to Patient

From:

To:

The recipient will receive more details and instructions to access this offer.

By clicking send, you acknowledge that you have permission to email the recipient with this information.

Email Forms to Patient

From:

To:

The recipient will receive more details and instructions to access this offer.

By clicking send, you acknowledge that you have permission to email the recipient with this information.

Previous
Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.