Anktiva

ANKTIVA in combination with Bacillus Calmette-Guérin (BCG) is indicated for the treatment of adult patients with BCG-unresponsive nonmuscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.

• For induction: 400 mcg administered intravesically with BCG once a week for 6 weeks. A second induction course may be administered if complete response is not achieved at month 3. (
  
  
  2.1 Recommended Dosage

  For Intravesical Use Only. Do NOT administer by subcutaneous or intravenous or intramuscular routes.

  • For induction: ANKTIVA is recommended at a dose of 400 mcg administered intravesically with BCG once a week for 6 weeks. A second induction course may be administered if complete response is not achieved at month 3.
  • For maintenance: After BCG and ANKTIVA induction therapy, ANKTIVA is recommended at a dose of 400 mcg administered intravesically with BCG once a week for 3 weeks at months 4, 7, 10, 13 and 19 (for a total of 15 doses). For patients with an ongoing complete response at month 25 and later, maintenance instillations with BCG may be administered once a week for 3 weeks at months 25, 31, and 37 for a maximum of 9 additional instillations.

  The recommended duration of treatment is until disease persistence after second induction, disease recurrence or progression, unacceptable toxicity, or a maximum of 37 months.
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• For maintenance: 400 mcg administered intravesically with BCG once a week for 3 weeks at months 4, 7, 10, 13 and 19. For patients with an ongoing complete response at month 25 and later, additional maintenance instillations with BCG may be administered once a week for 3 weeks at months 25, 31, and 37. (
  
  
  2.1 Recommended Dosage

  For Intravesical Use Only. Do NOT administer by subcutaneous or intravenous or intramuscular routes.

  • For induction: ANKTIVA is recommended at a dose of 400 mcg administered intravesically with BCG once a week for 6 weeks. A second induction course may be administered if complete response is not achieved at month 3.
  • For maintenance: After BCG and ANKTIVA induction therapy, ANKTIVA is recommended at a dose of 400 mcg administered intravesically with BCG once a week for 3 weeks at months 4, 7, 10, 13 and 19 (for a total of 15 doses). For patients with an ongoing complete response at month 25 and later, maintenance instillations with BCG may be administered once a week for 3 weeks at months 25, 31, and 37 for a maximum of 9 additional instillations.

  The recommended duration of treatment is until disease persistence after second induction, disease recurrence or progression, unacceptable toxicity, or a maximum of 37 months.
  )
  
  
  
  
  
• Instill intravesically only after dilution. Total time from vial puncture to the completion of the intravesical instillation should not exceed 2 hours. (
  
  
  2.2 Preparation and Administration

  Preparation of Agent

  
  
  See BCG Prescribing Information for information on preparation and handling of BCG.

  Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The solution is clear to slightly opalescent and colorless to slightly yellow. Discard the vial if visible particles are observed.

  Draw 0.4 mL of ANKTIVA into a small syringe and using aseptic technique add to the saline containing the BCG suspension that has been prepared following the instructions provided in the Prescribing Information for BCG. Mix the suspension gently. Using a 60-mL syringe connected to an appropriate size needle, withdraw the ANKTIVA BCG mixture to a final volume of 50 mL.

  If the admixture of ANKTIVA in combination with BCG is not used immediately, store refrigerated at 2°C to 8°C (36°F to 46°F) and use within 2 hours. Unused solution of admixture should be discarded after 2 hours.

  Treatment

  
  
  The admixture of ANKTIVA in combination with BCG is instilled into the bladder via a catheter. After instillation is complete, the catheter is removed. The ANKTIVA in combination with BCG admixture is retained in the bladder for 2 hours and then voided. Patients unable to retain the suspension for 2 hours should be allowed to void sooner, if necessary. Do not repeat the dose if the patient voids before 2 hours.

  See BCG Prescribing Information for information on retention in the bladder and patient positioning during bladder instillation.
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See full Prescribing Information for dilution and administration instructions.

400 mcg/0.4 mL, clear to slightly opalescent and colorless to slightly yellow solution in single-dose vials for intravesical instillation after dilution.

• Pregnancy: May cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. (
  
  
  8.1 Pregnancy

  Risk Summary

  
  
  Systemic exposure of nogapendekin alfa inbakicept-pmln following intravesical administration of the approved dosage of ANKTIVA was below the limit of quantitation

  [see Clinical Pharmacology 12.3)]

  .

  Based on its mechanism of action, ANKTIVA may cause fetal harm when administered to a pregnant woman if systemic exposure occurs

  [see Clinical Pharmacology ]

  . There are no available data on ANKTIVA use in pregnant women to inform a drug-associated risk. Animal reproductive and developmental toxicity studies have not been conducted with nogapendekin alfa inbakicept-pmln. Advise pregnant women and females of reproductive potential of the potential risk to a fetus.

  The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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.
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  8.3 Females and Males of Reproductive Potential

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

  [see Use in Specific Populations ]

  .

  Pregnancy Testing

  
  
  Verify pregnancy status in females of reproductive potential prior to initiating treatment with ANKTIVA.

  Contraception

  
  
  Advise females of reproductive potential to use effective contraception during treatment with ANKTIVA and for 1 week after the last dose.
  )
  

• Delaying cystectomy can lead to the development of metastatic bladder cancer, which can be lethal. (
  
  
  5.1 Risk of Metastatic Bladder Cancer with Delayed Cystectomy

  Delaying cystectomy in patients with BCG-unresponsive CIS could lead to development of muscle invasive or metastatic bladder cancer, which can be lethal. The risk of developing muscle invasive or metastatic bladder cancer increases the longer cystectomy is delayed in the presence of persisting CIS.

  Of the 77 evaluable patients with BCG-unresponsive CIS treated with ANKTIVA with BCG in QUILT-3.032, 10% (n = 8) progressed to muscle invasive (T2 or greater) bladder cancer, including 7 during the treatment period. Three patients had progression determined at the time of cystectomy. The median time between determination of persistent or recurrent CIS and progression to muscle-invasive disease was 107 days (range: 0 – 210).

  If patients with CIS do not have a complete response to treatment after a second induction course of ANKTIVA with BCG, reconsider cystectomy.
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