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BAVENCIO® (avelumab) in combination with INLYTA® (axitinib) dosing

  • Premedicate patients with an antihistamine and with acetaminophen prior to the first 4 infusions of BAVENCIO
    • Premedication should be administered for subsequent BAVENCIO doses based upon clinical judgment and presence/severity of prior infusion reactions
  • When INLYTA is used in combination with BAVENCIO, dose escalation of INLYTA above the initial 5-mg dose may be considered at intervals of two weeks or longer
    • Review the full Prescribing Information for INLYTA prior to initiation

The recommended dose of BAVENCIO is 800 mg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity

Adverse reaction management

  • Management of some adverse reactions may require temporary interruption or permanent discontinuation. See BAVENCIO Dose Modifications

Premedication

  • Premedicate patients with an antihistamine and with acetaminophen prior to the first 4 infusions of BAVENCIO
    • Premedication should be administered for subsequent BAVENCIO doses based on clinical judgment and presence/severity of prior infusion reactions

Preparation

  • Visually inspect vial for particulate matter and discoloration. BAVENCIO is a clear, colorless to slightly yellow solution. Discard vial if the solution is cloudy, discolored, or contains particulate matter
  • Withdraw the required volume of BAVENCIO from the vial(s) and inject it into a 250 mL infusion bag containing either 0.9% sodium chloride injection or 0.45% sodium chloride injection
  • Gently invert the bag to mix the diluted solution and avoid foaming or excessive shearing
  • Inspect the solution to ensure it is clear, colorless, and free of visible particles
  • Discard any partially used or empty vials

Storage of diluted BAVENCIO solution

  • Protect from light
  • Store diluted BAVENCIO solution:
    • At room temperature up to 77°F (25°C) for no more than 4 hours from the time of dilution
    • Or
    • Under refrigeration at 36°F to 46°F (2°C to 8°C) for no more than 24 hours from the time of dilution. If refrigerated, allow the diluted solution to come to room temperature prior to administration
  • Do not freeze or shake diluted solution

Administration

  • Administer the diluted solution over 60 minutes through an intravenous line containing a sterile, non-pyrogenic, low protein binding in-line filter (pore size of 0.2 micron)
  • Do not coadminister other drugs through the same intravenous line

Recommended dose modifications of BAVENCIO for adverse reactions

Severity of Adverse Reactions Dose Modifications

Grade 2 pneumonitis

Withhold BAVENCIO.

Resume BAVENCIO in patients with complete or partial resolution (Grade 0 to 1) of pneumonitis after corticosteroid taper.

Grade 3 or 4 pneumonitis or recurrent Grade 2 pneumonitis Permanently discontinue.
Severity of Adverse Reactions*

Grade 2 pneumonitis

Dose Modifications

Withhold BAVENCIO.

Resume BAVENCIO in patients with complete or partial resolution (Grade 0 to 1) of pneumonitis after corticosteroid taper.

Severity of Adverse Reactions*
Grade 3 or 4 pneumonitis or recurrent Grade 2 pneumonitis
Dose Modifications
Permanently discontinue.
Severity of Adverse Reactions Dose Modifications
Aspartate aminotransferase (AST)/or alanine aminotransferase (ALT) more than 3 and up to 5 times the upper limit of normal or total bilirubin more than 1.5 and up to 3 times the upper limit of normal

Withhold BAVENCIO.

Resume BAVENCIO in patients with complete or partial resolution (Grade 0 to 1) of hepatitis after corticosteroid taper.

AST or ALT more than 5 times the upper limit of normal or total bilirubin more than 3 times the upper limit of normal Permanently discontinue.
Severity of Adverse Reactions*

Aspartate aminotransferase (AST)/or alanine aminotransferase (ALT) more than 3 and up to 5 times the upper limit of normal or total bilirubin more than 1.5 and up to 3 times the upper limit of normal

Dose Modifications

Withhold BAVENCIO.

Resume BAVENCIO in patients with complete or partial resolution (Grade 0 to 1) of hepatitis after corticosteroid taper.

Severity of Adverse Reactions*
AST or ALT more than 5 times the upper limit of normal or total bilirubin more than 3 times the upper limit of normal
Dose Modifications
Permanently discontinue.

In patients with RCC being treated with BAVENCIO in combination with INLYTA:

  • If ALT or AST ≥3 times ULN but <5 times ULN or total bilirubin ≥1.5 times ULN but <3 times ULN, withhold both BAVENCIO and INLYTA until these adverse reactions recover to grades 0-1. If persistent (greater than 5 days), consider corticosteroid therapy [initial dose of 0.5 mg to 1 mg/kg/day] prednisone or equivalent followed by a taper. Consider rechallenge with a single drug or sequential rechallenge with both drugs after recovery. Dose reduce per the INLYTA full Prescribing Information if rechallenging with INLYTA
  • If ALT or AST ≥5 times ULN or >3 times ULN with concurrent total bilirubin ≥2 times ULN or total bilirubin ≥3 times ULN, permanently discontinue both BAVENCIO and INLYTA and consider corticosteroid therapy [initial dose 1 to 2 mg/kg/day prednisone or equivalent followed by taper]
Severity of Adverse Reactions Dose Modifications
Grade 2 or 3 diarrhea or colitis

Withhold BAVENCIO.

Resume BAVENCIO in patients with complete or partial resolution (Grade 0 to 1) of colitis or diarrhea after corticosteroid taper.

Grade 4 diarrhea or colitis or recurrent Grade 3 diarrhea or colitis Permanently discontinue.
Severity of Adverse Reactions*

Grade 2 or 3 diarrhea or colitis

Dose Modifications

Withhold BAVENCIO.

Resume BAVENCIO in patients with complete or partial resolution (Grade 0 to 1) of colitis or diarrhea after corticosteroid taper.

Severity of Adverse Reactions*
Grade 4 diarrhea or colitis or recurrent Grade 3 diarrhea or colitis
Dose Modifications
Permanently discontinue.
Severity of Adverse Reactions Dose Modifications
Grade 3 or 4

Withhold BAVENCIO.

Resume BAVENCIO in patients with complete or partial resolution (Grade 0 to 1) of endocrinopathies after corticosteroid taper.

Severity of Adverse Reactions*

Grade 3 or 4

Dose Modifications

Withhold BAVENCIO.

Resume BAVENCIO in patients with complete or partial resolution (Grade 0 to 1) of endocrinopathies after corticosteroid taper.

Severity of Adverse Reactions Dose Modifications
Serum creatinine more than 1.5 and up to 6 times the upper limit of normal

Withhold BAVENCIO.

Resume BAVENCIO in patients with complete or partial resolution (Grade 0 to 1) of nephritis and renal dysfunction after corticosteroid taper.

Serum creatinine more than 6 times the upper limit of normal Permanently discontinue.
Severity of Adverse Reactions*

Serum creatinine more than 1.5 and up to 6 times the upper limit of normal

Dose Modifications

Withhold BAVENCIO.

Resume BAVENCIO in patients with complete or partial resolution (Grade 0 to 1) of nephritis and renal dysfunction after corticosteroid taper.

Severity of Adverse Reactions*
Serum creatinine more than 6 times the upper limit of normal
Dose Modifications
Permanently discontinue.
Severity of Adverse Reactions Dose Modifications
For any of the following:
  • Moderate or severe clinical signs or symptoms of an immune-mediated adverse reaction not described above
  • Grade 3 or 4 endocrinopathies

Withhold BAVENCIO.

Resume BAVENCIO in patients with complete or partial resolution (Grade 0 to 1) of other immune-mediated adverse reactions after corticosteroid taper.

For any of the following:
  • Life-threatening adverse reaction (excluding endocrinopathies)
  • Recurrent severe immune-mediated adverse reaction
  • Requirement for 10 mg per day or greater prednisone or equivalent for more than 12 weeks
  • Persistent Grade 2 or 3 immune-mediated adverse reactions lasting 12 weeks or longer

Permanently discontinue.

Severity of Adverse Reactions*

For any of the following:

  • Moderate or severe clinical signs or symptoms of an immune-mediated adverse reaction not described above
  • Grade 3 or 4 endocrinopathies
Dose Modifications

Withhold BAVENCIO pending clinical evaluation.

Resume BAVENCIO in patients with complete or partial resolution (Grade 0 to 1) of other immune-mediated adverse reactions after corticosteroid taper.

Severity of Adverse Reactions*

For any of the following:

  • Life-threatening adverse reaction (excluding endocrinopathies)
  • Recurrent severe immune-mediated adverse reaction
  • Requirement for 10 mg per day or greater prednisone or equivalent for more than 12 weeks
  • Persistent Grade 2 or 3 immune-mediated adverse reactions lasting 12 weeks or longer
Dose Modifications
Permanently discontinue.
Severity of Adverse Reactions Dose Modifications
Grade 1 or 2 Interrupt or slow the rate of infusion.
Grade 3 or 4 Permanently discontinue.
Severity of Adverse Reactions*

Grade 1 or 2

Dose Modifications

Interrupt or slow the rate of infusion.

Severity of Adverse Reactions*
Grade 3 or 4
Dose Modifications
Permanently discontinue.

 

*Observed with BAVENCIO or with other anti-PD-1/PD-L1 monoclonal antibodies.

Starting dose for most patients is 5 mg orally taken twice daily

  • Dose titration
    • Dose can be increased or decreased based on individual safety and tolerability  

  • Half-life
    • The half-life of INLYTA ranges from 2.5 to 6.1 hours
INLYTA dosing considerations
  • For patients with moderate hepatic impairment, or for patients on a strong CYP3A4/5 inhibitor, decrease the INLYTA dose by approximately half
  • Avoid strong CYP3A4/5 inhibitors. If unavoidable reduce the dose
  • Avoid strong CYP3A4/5 inducers and, if possible, avoid moderate CYP3A4/5 inducers
  • Patients should not eat grapefruit, drink grapefruit juice, or take St John's wort while taking INLYTA
  • Stop treatment with INLYTA at least 2 days prior to elective surgery. Do not re-administer INLYTA for at least 2 weeks following major surgery and until adequate wound healing

Management of some AEs may require temporary interruption or permanent discontinuation and/or dose reduction

  • The dose of INLYTA may be increased or reduced based on individual safety or tolerability
  • Film-coated tablets in 2 different strengths (5 mg and 1 mg) allow for titration
  • Do not break apart INLYTA tablets

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Dose modification criteria

If a dose reduction from the starting dose is required:

  • Reduce dose to 3 mg twice daily
  • Reduce dose to 2 mg twice daily if additional dose reduction is required

 

Dose increase criteria: Patients tolerate INLYTA for at least 2 consecutive weeks with no AEs >Grade 2 and are normotensive without antihypertension medication

  • Dose may be increased to 7 mg twice daily if patients meet dose increase criteria at the starting dose
  • Dose may be further increased to 10 mg twice daily if patients meet the dose increase criteria at the 7-mg dose