tebentafusp

Therapeutic Classification: antineoplastics

Pharmacologic Classification: T-cell engagers

High Alert

HLA-A*02:01-positive patients with unresectable or metastatic uveal melanoma.

Binds to a gp100 peptide presented by HLA-A*02:01 on the surface of uveal melanoma tumor cells. Once bound, this complex acts as a T-cell engager, binding to the CD3 receptor on T-cells. T cells are then activated, which causes release of proinflammatory cytokines, resulting in direct lysis of uveal melanoma tumor cells.

Therapeutic effects:

Improved overall survival and progression-free survival.

Absorption: IV administration results in complete bioavailability.

Distribution: Minimal distribution to tissues.

Metabolism/Excretion: Broken down into small peptides and amino acids. Excretion pathway unknown.

Half-Life: 7.5 hr.

(increase in proinflammatory cytokine concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	8–24 hr	unknown‡

‡Concentrations returned to baseline before next dose.

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

CV: edema, hypotension, hypertension, tachycardia

Derm: cutaneous edema, dry skin, erythema, hair color changes, hypopigmentation, pruritus, rash, alopecia, flushing, hyperpigmentation

Endo: hyperglycemia, hypoglycemia

F and E: hypercalcemia, hyperkalemia, hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia

GI: ↑amylase, ↑lipase, ↑liver enzymes, abdominal pain, diarrhea, hyperbilirubinemia, hypoalbuminemia, nausea, vomiting, constipation, oropharyngeal pain

GU: ↑serum creatinine

Hemat: anemia, lymphocytopenia, neutropenia, thrombocytopenia

Metab: ↓appetite

MS: arthralgia, muscle spasm, myalgia, pain

Neuro: fatigue, headache, dizziness, paresthesia

Resp: dyspnea

Misc: chills, cytokine release syndrome (CRS), fever, night sweats

Drug-drug:

None reported.

IV (Adults ): Day 1: 20 mcg as single dose; Day 8: 30 mcg as single dose; Day 15: 68 mcg as single dose; Day 22 and beyond: 68 mcg once weekly until disease progression or unacceptable toxicity.

Solution for injection: 100 mcg/0.5 mL

Monitor for CRS during and ≥16 hr after infusion complete. If moderate CRS (temperature ≥100.4°F, hypotension responsive to fluids, or hypoxia requiring oxygen at ≤6 L/min) lasts 2–3 hr or recurs, administer dexamethasone 4 mg or equivalent ≥30 min prior to next dose. If moderate hypotension and hypoxia do not improve in 3 hr or worsen, manage at next higher severity level. If severe CRS (temperature ≥100.4°F, hypotension requiring vasopressor, or worsening hypoxia/dyspnea requiring oxygen at >6 L/min or face mask) occurs, hold infusion until symptoms resolve. Administer methylprednisolone 2 mg/kg/day or equivalent and resume at same tebentafusp dose. Do not escalate dose if severe CRS occurred during 1st dose escalation; may escalate dose once tolerated. Administer dexamethasone 4 mg or equivalent ≥30 min prior to next dose. If life-threatening CRS (temperature ≥100.4°F; hypotension requiring multiple vasopressors, including vasopressin; or worsening hypoxia/dyspnea despite oxygen administration with positive pressure) occurs, permanently discontinue tebentafusp and administer methylprednisolone 2 mg/kg/day or equivalent.
Monitor for hypotension during and for ≥16 hr after 1st three infusions. If no Grade 2 or worse hypotension occurs after 3rd infusion, may monitor for ≥30 min following subsequent infusions.
Monitor for skin reactions (rash, pruritus, erythema, cutaneous edema) for 1–6 days after infusion. For Grade 2–3 skin reactions, hold tebentafusp until Grade ≤1. Resume at same dose. Do not escalate dose if Grade 3 reaction occurred during initial dose escalation; may escalate dose once tolerated. Consider methylprednisolone 2 mg/kg/day or equivalent for persistent reactions not responsive to antihistamine or topical or oral steroids. For Grade 4 skin reactions, permanently discontinue tebentafusp. Administer methylprednisolone 2 mg/kg/day or equivalent.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
Monitor ALT, AST and total bilirubin at baseline and during therapy. For Grade 3–4 ↑ in liver enzymes, hold tebentafusp until Grade ≤1. Resume at same dose if ↑ liver enzymes are concurrent with Grade 3 CRS; resume dose escalation if next dose tolerated. If ↑ liver enzymes are unrelated to Grade 3 CRS, resume at same dose or escalate if current dose <68 mcg. Administer IV corticosteroid if no improvement in 24 hr.

Keep appropriate resuscitation equipment and medication nearby.

IV Administration:

Intermittent Infusion: To prevent absorption of tebentafusp to the infusion bag, prepare an infusion bag made of polyolefins and polypropylene or PVC with albumin. Inject the following calculated volume of albumin into 100-mL bag of 0.9% NaCl: 0.5 mL of albumin 5%; 0.13 mL of albumin 20%; 0.1 mL of albumin 25%. Invert infusion bag so entry port is on top; tap the side of the port tubing to release any residual solution. Repeat an additional 3 times. Do not shake.Diluent: Withdraw volume of tebentafusp from vial for required dose and add to prepared infusion bag of 0.9% NaCl with albumin. Mix infusion bag following the above procedure. Solution is clear, colorless to slightly yellow, do not use if cloudy, discolored or contains particulates.Concentration: 0.2–0.68 mcg/mLRate: Infuse over 15–20 min.Administer within 4 hr, including infusion time, through a dedicated IV line with nonpyrogenic low-protein-binding 0.2-micron in-line filter. May refrigerate for <24 hr, including time to bring solution to room temperature and infusion time.
Y-Site Incompatibility: Do not administer other drugs through same IV line.

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care professional for symptoms of CRS (fever, fatigue, dizziness, nausea, headache, muscle and joint pain).
Advise patient to notify health care professional for progressive or intolerable skin reactions.
Advise patient to notify health care professional for signs and symptoms of liver toxicity (right-sided abdominal pain, jaundice).
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception and to not breastfeed during and for 1 wk after last dose. Advise patient to notify health care professional if pregnancy is planned or suspected.

Improved overall survival and progression-free survival.

NDC Code

80446- Immunocore Commercial LLC
- 80446-401- KIMMTRAK
  - 80446-401-01- 1 VIAL, GLASS in 1 CARTON (80446-401-01) / .5 mL in 1 VIAL, GLASS

82507- AGC Biologics A/S
- 82507-003-
  - 82507-003-01- 2000 mL in 1 BOTTLE (82507-003-01)

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