Nogapendekin Alfa Inbakicept-pmln (Monograph)

Brand name: Anktiva
Drug class: Antineoplastic Agents

Introduction

Interleukin-15 (IL-15) receptor agonist; antineoplastic agent.

Uses for Nogapendekin Alfa Inbakicept-pmln

Bladder Cancer

Used intravesically 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 (Ta or T1).

NMIBC is usually treated initially with surgical resection and/or fulguration. NMIBC includes papillary tumors limited to the epithelial mucosa (stage Ta), tumors invading the subepithelial tissue but not extending beyond the lamina propria of the bladder (stage T1), and CIS (stage Tis).

Intravesical BCG is the standard of care for patients with high risk of recurrence of NMIBC, including CIS, high-grade Ta, and T1 disease, following transurethral resection (TUR). However, up to 40–50% of patients fail BCG therapy. For BCG-unresponsive CIS, the International Bladder Cancer Group supports nogapendekin alfa inbakicept-pmln plus BCG as a bladder-sparing option.

Nogapendekin Alfa Inbakicept-pmln Dosage and Administration

General

Pretreatment Screening

Verify pregnancy status in females of reproductive potential.

Administration

Intravesical Administration

Administer by intravesical installation into the bladder. Do not administer by sub-Q, IV, or IM routes.

Must be administered with BCG and diluted before administration.

Available as a 400 mcg/0.4 mL solution in single-dose vials.

Dilution

Prepare the BCG suspension according to the BCG prescribing information.

Using aseptic technique, withdraw 0.4 mL of nogapendekin alfa inbakicept-pmln into a small syringe and add to the prepared BCG saline suspension. Gently mix, then transfer the admixture to a 60-mL syringe to a final volume of 50 mL.

Intravesical Administration

Instill the admixture into the bladder using a catheter, then remove the catheter. Patients should retain the solution for 2 hours before voiding; if unable to do so, earlier voiding is permitted, but the dose should not be repeated. Refer to the BCG prescribing information for additional guidance on retention and positioning.

Dosage

Adults

Bladder Cancer

Intravesical

Induction therapy: Administer 400 mcg with BCG once weekly for 6 weeks. Give a second induction course if the patient does not achieve a complete response by 3 months.

Maintenance therapy: After induction, administer 400 mcg with BCG once weekly for 3 weeks at months 4, 7, 10, 13, and 19 (15 doses total). If patient maintains a complete response at 25 months or later, may administer additional maintenance instillations with BCG once weekly for 3 weeks at months 25, 31, and 37 (up to 9 additional doses).

Continue treatment until lack of response after the second induction course, disease recurrence or progression, unacceptable toxicity, or a maximum of 37 months.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

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 CIS increases risk of progression to muscle-invasive or metastatic bladder cancer. If CIS persists after a second induction course, reconsider cystectomy.

Immunogenicity

insufficient information to characterize anti-drug antibody response to nogapendekin alfa inbakicept-pmln and the effects of such antibodies on pharmacokinetics, pharmacodynamics, safety, or effectiveness of the drug.

Specific Populations

Pregnancy

Minimal systemic absorption after intravesical use, but may cause fetal harm if exposure occurs; no human or animal reproductive data available.

Advise pregnant women and females of reproductive potential of the potential risk to a fetus.

Lactation

Minimal systemic absorption after intravesical use; presence in human milk is unknown. While exposure to the breastfed child is likely low, weigh benefits of breastfeeding against mother’s need for treatment and potential risks.

Females and Males of Reproductive Potential

May cause fetal harm based on mechanism of action.

Verify pregnancy status before treatment, and advise females of reproductive potential to use effective contraception during therapy and for 1 week after the last dose.

Pediatric Use

Safety and effectiveness not established.

Geriatric Use

In clinical studies, most patients were older adults (84% ≥65 years of age; 40% ≥75 years of age), with too few younger patients to evaluate age-related differences in response.

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, pyrexia.

Nogapendekin Alfa Inbakicept-pmln Pharmacokinetics

Absorption

Patients who received the approved dose of nogapendekin alfa inbakicept-pmln did not exhibit quantifiable systemic exposure.

Stability

Storage

Intravesical

Solution

Store vials under refrigeration at 2–8°C in original carton to protect from light. Do not freeze; do not shake.

If diluted solution not used immediately, refrigerate at 2–8°C and use within 2 hours; discard any unused solution.

Actions

IL-15 receptor agonist.
Activates IL-15 pathways to expand NK cells, CD8⁺ T cells, and memory T cells by binding the IL-2/IL-15 receptor, without stimulating regulatory T cells.
Recombinant protein complex consisting of nogapendekin alfa (a human IL-15N72D variant) bound to inbakicept (a dimeric human IL-15Rα sushi domain/human IgG1 Fc fusion protein).

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 possible risk to the fetus. Advise patients 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.
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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.

Nogapendekin alfa inbakicept-pmln is obtained through designated specialty pharmacies. Contact the manufacturer or consult the ANKTIVA website ([Web]).