Nogapendekin Alfa Inbakicept-pmln (Monograph)

Brand name: Anktiva
Drug class: Antineoplastic Agents

Introduction

Nogapendekin alfa inbakicept-pmln, an interleukin-15 (IL-15) receptor agonist, is an antineoplastic agent.

Uses for Nogapendekin Alfa Inbakicept-pmln

Nogapendekin alfa inbakicept has the following uses:

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

Nogapendekin Alfa Inbakicept-pmln Dosage and Administration

General

Nogapendekin alfa inbakicept-pmln is available in the following dosage form(s) and strength(s):

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

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

For intravesical use only; do not administer by subcutaneous or IV or IM routes.

Instill intravesically only after dilution. See Full Prescribing Information for dilution and administration instructions. Total time from vial puncture to the completion of the intravesical instillation should not exceed 2 hours.
Recommended dosage 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.
Recommended dosage for maintenance: 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, additional 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.

Cautions for Nogapendekin Alfa Inbakicept-pmln

Contraindications

None.

Warnings/Precautions

Risk of Metastatic Bladder Cancer with Delayed Cystectomy

Delaying cystectomy in patients with BCG-unresponsive carcinoma in situ (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 nogapendekin alfa inbakicept-pmln with BCG in the QUILT-3.032 study, 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 nogapendekin alfa inbakicept with BCG, reconsider cystectomy.

Specific Populations

Pregnancy

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

Based on its mechanism of action, nogapendekin alfa inbakicept-pmln may cause fetal harm when administered to a pregnant woman if systemic exposure occurs. There are no available data on use of the drug 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.

Lactation

There are no data on the presence of nogapendekin alfa inbakicept-pmln in human milk, or the effects on the breastfed child, or on milk production. Systemic exposure of nogapendekin alfa inbakicept-pmln in patients receiving intravesical administration at the approved dosage was below the limit of quantitation, indicating any amount in the milk will be low. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for nogapendekin alfa inbakicept and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition.

Females and Males of Reproductive Potential

Based on its mechanism of action, nogapendekin alfa inbakicept-pmln may cause fetal harm when administered to a pregnant woman.

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

Advise females of reproductive potential to use effective contraception during treatment with nogapendekin alfa inbakicept-pmln and for 1 week after the last dose.

Pediatric Use

Safety and effectiveness of nogapendekin alfa inbakicept-pmln in pediatric patients have not been established.

Geriatric Use

Of the total number of patients in clinical studies of nogapendekin alfa inbakicept-pmln for BCG-unresponsive NMIBC, 84% were 65 years of age or older and 40% were 75 years or older. Clinical studies of nogapendekin alfa inbakicept-pmln did not include sufficient numbers of younger adult patients to determine if patients 65 years of age and older respond differently than younger adult patients.

Common Adverse Effects

The most common (≥15%) adverse reactions, including laboratory test abnormalities, are increased creatinine, dysuria, hematuria, urinary frequency, micturition urgency, urinary tract infection, increased potassium, musculoskeletal pain, chills and pyrexia.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Nogapendekin alfa inbakicept-pmln is an IL-15 receptor agonist. IL-15 signals through a heterotrimeric receptor that is composed of the common gamma chain (γc) subunit, the beta chain (βc) subunit, and the IL-15-specific alpha subunit, IL-15 receptor α. IL-15 is trans-presented by the IL-15 receptor α to the shared IL-2/IL-15 receptor (βc and γc) on the surface of CD4 ⁺ and CD8 ⁺T cells and NK cells.

Binding of nogapendekin alfa inbakicept to its receptor results in proliferation and activation of NK, CD8 ⁺, and memory T cells without proliferation of immuno-suppressive Treg cells. In vivo, intravesicular nogapendekin alfa inbakicept-pmln alone or in combination with BCG showed anti-tumor activity when compared to BCG alone, in a carcinogen-induced model of bladder cancer in immunocompetent rats.

Advice to Patients

Inform patients that delaying cystectomy could lead to development of metastatic bladder cancer. Discuss the risk of metastatic bladder cancer and that the risk increases the longer cystectomy is delayed in the presence of persisting carcinoma in situ (CIS).
Inform patients that irritable bladder symptoms may occur during instillation, and retention of nogapendekin alfa inbakicept, and following voiding.
Inform patients that for the first 24 hours following administration, red-tinged urine may occur.
Advise patients to immediately report prolonged irritable bladder symptoms or prolonged passage of red-colored urine to their healthcare provider.
Instruct patients to maintain adequate hydration following nogapendekin alfa inbakicept treatment.
Inform patients that the nogapendekin alfa inbakicept in combination with BCG admixture should be retained in the bladder for 2 hours and then voided.
Advise patients that if unable to retain the suspension for 2 hours, they can void sooner if necessary.
Instruct patients to void while seated to avoid splashing of urine.
Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy.
Advise females of reproductive potential to use effective contraception during treatment with nogapendekin alfa inbakicept and for 1 week after the last dose.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.