Kimmtrak

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

• Recommended dosage: 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 (
  2.2 Recommended Dosage

  The recommended dosage of KIMMTRAK administered intravenously is:

  • 20 mcg on Day 1
  • 30 mcg on Day 8
  • 68 mcg on Day 15
  • 68 mcg once every week thereafter

  Treat patients until unacceptable toxicity or disease progression occur.

  Administer the first three infusions of KIMMTRAK in an appropriate healthcare setting by intravenous infusion over 15-20 minutes. Monitor patients during the infusion and for at least 16 hours after the infusion is complete.

  If the patient does not experience Grade 2 or worse hypotension (requiring medical intervention) during or after the third infusion, administer subsequent doses in an appropriate ambulatory care setting, and monitor patients for a minimum of 30 minutes following each of these infusions

  [see Warnings and Precautions (5.1)]

  .
  ).
• Dilute and administer by intravenous infusion over 15-20 minutes (
  2.2 Recommended Dosage

  The recommended dosage of KIMMTRAK administered intravenously is:

  • 20 mcg on Day 1
  • 30 mcg on Day 8
  • 68 mcg on Day 15
  • 68 mcg once every week thereafter

  Treat patients until unacceptable toxicity or disease progression occur.

  Administer the first three infusions of KIMMTRAK in an appropriate healthcare setting by intravenous infusion over 15-20 minutes. Monitor patients during the infusion and for at least 16 hours after the infusion is complete.

  If the patient does not experience Grade 2 or worse hypotension (requiring medical intervention) during or after the third infusion, administer subsequent doses in an appropriate ambulatory care setting, and monitor patients for a minimum of 30 minutes following each of these infusions

  [see Warnings and Precautions (5.1)]

  .
  ,
  2.4 Preparation and Administration

  Preparation

  • A 2-step dilution process is required for preparation of the final KIMMTRAK dose for infusion.
  • Use aseptic technique for dilution and preparation of intravenous infusion solutions.
  • Visually inspect parenteral drug products and infusion bags for particulate matter and discoloration prior to administration, whenever solution and container permit.

  Step 1: Preparation of the Infusion Bag

  To prevent adsorption of tebentafusp-tebn to the infusion bag and other components of the drug delivery system, prepare an Albumin (Human) in 0.9% Sodium Chloride Injection, USP solution as follows:

  • Using a 1 mL syringe with graduations of 2 decimal places and a sterile needle, withdraw the calculated volume of Albumin (Human) into the syringe (see Table 2below) and add to the 100 mL 0.9% Sodium Chloride Injection, USP bag constructed of polyolefins (PO) [such as polyethylene (PE) and polypropylene (PP)] or polyvinyl chloride (PVC) to make a final Albumin (Human) concentration of 250 mcg/mL.
    Table 2: Examples of Albumin (Human) Concentration and Volumes

    *Albumin (Human); use concentration as per local availability. Examples include but are not restricted to the following strengths: 5%, 20%, or 25%.
    Albumin (Human) concentration*	Albumin (Human) volume for addition to a 100 mL 0.9% Sodium Chloride Injection, USP Infusion Bag to prepare a concentration of 250 mcg/mL Albumin (Human) in 0.9% Sodium Chloride Injection, USP
    5% (50 g/L)	0.5 mL
    20% (200 g/L)	0.13 mL
    25% (250 g/L)	0.1 mL

  • Gently homogenize the prepared solution by completing the following steps:
    • Invert the infusion bag so that the bag is upside down with the entry port positioned on top. Then tap the side of the port tubing to ensure that any residual solution is released into the bulk solution.
    • Mix the prepared solution by gently rotating the bag lengthwise 360 degrees from the inverted position at least 5 times.
      Do not shake the infusion bag.
    • Repeat (i) and (ii) an additional three times.

  Step 2- Preparation of KIMMTRAK Solution for Infusion

  • Do not shake the KIMMTRAK vial.
  • Using a 1 mL syringe with graduations of 2 decimal places and a sterile needle, withdraw the required volume of KIMMTRAK 100 mcg/ 0.5 mL as per the dose required (shown in Table 3below) and add to the prepared 100 mL infusion bag containing 0.9% Sodium Chloride Injection, USP plus Albumin (Human).
  • Discard the single-dose vial containing the unused portion of KIMMTRAK in accordance with local requirements. Do not prepare more than one dose from the vial.
    Table 3: KIMMTRAK Volumes Required for Addition to the Infusion Bag

    Day of treatment	Dose (mcg) of KIMMTRAK	Volume (mL) of KIMMTRAK
    Day 1	20	0.1
    Day 8	30	0.15
    Day 15 and weekly thereafter	68	0.34

  • Mix the infusion bag by following the same procedure outlined in Step 1b.

  Administration

  • Immediately administer the diluted solution via intravenous infusion over 15-20 minutes through a dedicated intravenous line. A sterile, non-pyrogenic, low protein binding 0.2 micron in-line filter infusion set should be used. Administer the entire contents of the KIMMTRAK infusion bag.
  • Administer the prepared infusion bag within 4 hours from the time of preparation including the duration of infusion. During the 4-hour window, the KIMMTRAK infusion bag should remain at room temperature.
  • If not used immediately, store the KIMMTRAK infusion bag in a refrigerator at 2°C to 8°C (36°F to 46°F) and infuse within 24 hours from the time of preparation, which includes the storage time in the refrigerator, the time allowed for equilibration of the infusion bag to room temperature, and the duration of the infusion.
  • Once removed from the refrigerator, do not refrigerate KIMMTRAK infusion bag again. Do not freeze. Discard unused KIMMTRAK solution beyond the recommended storage time.
  • Do not mix KIMMTRAK with other drugs or administer other drugs through the same intravenous line.
  • Upon completion of KIMMTRAK infusion, flush the infusion line with adequate volume of sterile 0.9% Sodium Chloride Injection, USP to ensure that the entire contents of the infusion bag are administered.
  ).
• See Full Prescribing Information for instructions on preparation and administration of the diluted solution for intravenous infusion (
  2.2 Recommended Dosage

  The recommended dosage of KIMMTRAK administered intravenously is:

  • 20 mcg on Day 1
  • 30 mcg on Day 8
  • 68 mcg on Day 15
  • 68 mcg once every week thereafter

  Treat patients until unacceptable toxicity or disease progression occur.

  Administer the first three infusions of KIMMTRAK in an appropriate healthcare setting by intravenous infusion over 15-20 minutes. Monitor patients during the infusion and for at least 16 hours after the infusion is complete.

  If the patient does not experience Grade 2 or worse hypotension (requiring medical intervention) during or after the third infusion, administer subsequent doses in an appropriate ambulatory care setting, and monitor patients for a minimum of 30 minutes following each of these infusions

  [see Warnings and Precautions (5.1)]

  .
  ,
  2.4 Preparation and Administration

  Preparation

  • A 2-step dilution process is required for preparation of the final KIMMTRAK dose for infusion.
  • Use aseptic technique for dilution and preparation of intravenous infusion solutions.
  • Visually inspect parenteral drug products and infusion bags for particulate matter and discoloration prior to administration, whenever solution and container permit.

  Step 1: Preparation of the Infusion Bag

  To prevent adsorption of tebentafusp-tebn to the infusion bag and other components of the drug delivery system, prepare an Albumin (Human) in 0.9% Sodium Chloride Injection, USP solution as follows:

  • Using a 1 mL syringe with graduations of 2 decimal places and a sterile needle, withdraw the calculated volume of Albumin (Human) into the syringe (see Table 2below) and add to the 100 mL 0.9% Sodium Chloride Injection, USP bag constructed of polyolefins (PO) [such as polyethylene (PE) and polypropylene (PP)] or polyvinyl chloride (PVC) to make a final Albumin (Human) concentration of 250 mcg/mL.
    Table 2: Examples of Albumin (Human) Concentration and Volumes

    *Albumin (Human); use concentration as per local availability. Examples include but are not restricted to the following strengths: 5%, 20%, or 25%.
    Albumin (Human) concentration*	Albumin (Human) volume for addition to a 100 mL 0.9% Sodium Chloride Injection, USP Infusion Bag to prepare a concentration of 250 mcg/mL Albumin (Human) in 0.9% Sodium Chloride Injection, USP
    5% (50 g/L)	0.5 mL
    20% (200 g/L)	0.13 mL
    25% (250 g/L)	0.1 mL

  • Gently homogenize the prepared solution by completing the following steps:
    • Invert the infusion bag so that the bag is upside down with the entry port positioned on top. Then tap the side of the port tubing to ensure that any residual solution is released into the bulk solution.
    • Mix the prepared solution by gently rotating the bag lengthwise 360 degrees from the inverted position at least 5 times.
      Do not shake the infusion bag.
    • Repeat (i) and (ii) an additional three times.

  Step 2- Preparation of KIMMTRAK Solution for Infusion

  • Do not shake the KIMMTRAK vial.
  • Using a 1 mL syringe with graduations of 2 decimal places and a sterile needle, withdraw the required volume of KIMMTRAK 100 mcg/ 0.5 mL as per the dose required (shown in Table 3below) and add to the prepared 100 mL infusion bag containing 0.9% Sodium Chloride Injection, USP plus Albumin (Human).
  • Discard the single-dose vial containing the unused portion of KIMMTRAK in accordance with local requirements. Do not prepare more than one dose from the vial.
    Table 3: KIMMTRAK Volumes Required for Addition to the Infusion Bag

    Day of treatment	Dose (mcg) of KIMMTRAK	Volume (mL) of KIMMTRAK
    Day 1	20	0.1
    Day 8	30	0.15
    Day 15 and weekly thereafter	68	0.34

  • Mix the infusion bag by following the same procedure outlined in Step 1b.

  Administration

  • Immediately administer the diluted solution via intravenous infusion over 15-20 minutes through a dedicated intravenous line. A sterile, non-pyrogenic, low protein binding 0.2 micron in-line filter infusion set should be used. Administer the entire contents of the KIMMTRAK infusion bag.
  • Administer the prepared infusion bag within 4 hours from the time of preparation including the duration of infusion. During the 4-hour window, the KIMMTRAK infusion bag should remain at room temperature.
  • If not used immediately, store the KIMMTRAK infusion bag in a refrigerator at 2°C to 8°C (36°F to 46°F) and infuse within 24 hours from the time of preparation, which includes the storage time in the refrigerator, the time allowed for equilibration of the infusion bag to room temperature, and the duration of the infusion.
  • Once removed from the refrigerator, do not refrigerate KIMMTRAK infusion bag again. Do not freeze. Discard unused KIMMTRAK solution beyond the recommended storage time.
  • Do not mix KIMMTRAK with other drugs or administer other drugs through the same intravenous line.
  • Upon completion of KIMMTRAK infusion, flush the infusion line with adequate volume of sterile 0.9% Sodium Chloride Injection, USP to ensure that the entire contents of the infusion bag are administered.
  ).
• Dosage interruption or permanent discontinuation may be required based on individual safety and tolerability (
  2.3 Dosage Modifications for Adverse Reactions

  No dosage reduction for KIMMTRAK is recommended. Dosage modifications for KIMMTRAK for adverse reactions are summarized in Table 1.

  Table 1: Dose Modifications for Adverse Reactions

  aBased on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (NCI CTCAEv4.03).
  Adverse Reaction	Severity	KIMMTRAK Dosage Modifications
  Cytokine Release Syndrome (CRS) [see Warnings and Precautions (5.1)]	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 hours or CRS worsens, escalate care and manage according to next higher level of severity For moderate CRS that is persistent (lasting 2-3 hours) or recurrent, administer corticosteroid premedication (e.g. dexamethasone 4 mg or equivalent) at least 30 minutes prior to 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 KIMMTRAK until CRS and sequelae have resolved Administer intravenous corticosteroid (e.g., 2 mg/kg/day methylprednisolone or equivalent) Resume KIMMTRAK at same dose level (i.e., do not escalate if severe CRS occurred during initial dose escalation; resume escalation once dosage is tolerated) For severe CRS, administer corticosteroid premedication (e.g. dexamethasone 4 mg or equivalent) at least 30 minutes prior to next dose
  	Life threatening defined as temperature ≥ 38°C with Hemodynamic instability requiring multiple vasopressors (excluding vasopressin) Worsening hypoxia or respiratory distress despite oxygen administration requiring positive pressure	Permanently discontinue KIMMTRAK Administer intravenous corticosteroid (e.g., 2 mg/kg/day methylprednisolone or equivalent)
  Skin Reactions [see Warnings and Precautions (5.2)]	Grade 2 or 3a	Withhold KIMMTRAK until ≤ Grade 1 or baseline Resume KIMMTRAK at same dose level (i.e., do not escalate if Grade 3 skin reactions occurred during initial dose escalation; resume escalation once dosage is tolerated) For persistent reactions not responding to oral steroids, consider intravenous corticosteroid (e.g., 2 mg/kg/day methylprednisolone or equivalent)
  	Grade 4a	Permanently discontinue KIMMTRAK Administer intravenous corticosteroid (e.g., 2 mg/kg/day methylprednisolone or equivalent)
  Elevated Liver Enzymes [see Warnings and Precautions (5.3)]	Grade 3 or 4a	Withhold KIMMTRAK until ≤ Grade 1 or baseline. Resume KIMMTRAK at same dose level if the elevated liver enzymes occur in the setting of Grade 3 CRS; resume escalation if next administration is tolerated. If the elevated liver enzymes occur outside the setting of Grade 3 CRS resume escalation if the current dose is less than 68 mcg, or resume at same dose level if dose escalation has completed Administer intravenous corticosteroids if no improvement within 24 hours
  Other Adverse Reactions [see Adverse Reactions (6.1)]	Grade 3a	Withhold KIMMTRAK until ≤ Grade 1 or baseline Resume KIMMTRAK at same dose level (i.e., do not escalate if other Grade 3 adverse reaction occurred during initial dose escalation; resume escalation once dosage is tolerated)
  	Grade 4a	Permanently discontinue KIMMTRAK
  ).

Injection: 100 mcg/0.5 mL clear, colorless to slightly yellowish solution in a single-dose vial

Based on the mechanism of action, KIMMTRAK may cause fetal harm when administered to a pregnant woman

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.