Nogapendekin alfa inbakicept

Nogapendekin alfa inbakicept – Description

• Nogapendekin alfa inbakicept-pmln is an interleukin-15 receptor agonist.
• It is indicated in combination with Bacillus Calmette-Guerin (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.
• It is for intravesical administration only.⁷⁰⁵⁴³

Indications & Dosage

•  Bladder cancer

For the treatment of bladder cancer

For the treatment of Bacillus Calmette-Guerin (BCG)-unresponsive nonmuscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors, in combination with BCG

Maximum Dosage Limits:

•Adults

400 mcg intravesically.

•Geriatric

400 mcg intravesically.

•Adolescents

Safety and efficacy have not been established.

•Children

Safety and efficacy have not been established.

•Infants

Safety and efficacy have not been established.

•Neonates

Safety and efficacy have not been established.

Patients with Hepatic Impairment Dosing

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Patients with Renal Impairment Dosing

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Precautions

•  breast-feeding
•  contraception requirements
•  pregnancy
•  pregnancy testing
•  reproductive risk
•  surgery

Pregnancy

• Pregnancy should be avoided by females of reproductive potential during nogapendekin alfa inbakicept treatment and for 1 week after the last dose.
• Although there are no adequately controlled studies in pregnant women or animals, nogapendekin alfa inbakicept can cause fetal harm when administered during pregnancy based on its mechanism of action.
• Systemic exposure of nogapendekin alfa inbakicept was below the limit of quantification following intravesical administration of the FDA approved dose. Women who are pregnant or who become pregnant while receiving nogapendekin alfa inbakicept should be apprised of the potential hazard to the fetus.⁷⁰⁵⁴³

Lactation

• Consider the developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for nogapendekin alfa inbakicept and any potential adverse effects on the breastfed child.
• It is not known whether nogapendekin alfa inbakicept is present in human milk, although many drugs are excreted in human milk.
• Systemic exposure of nogapendekin alfa inbakicept was below the limit of quantification following intravesical administration of the FDA approved dose.

Interactions

There are no drug interactions associated with Nogapendekin alfa inbakicept products.

Adverse Reactions

•  bladder discomfort
•  chills
•  diarrhea
•  dysuria
•  fatigue
•  fever
•  hematuria
•  hyperkalemia
•  increased urinary frequency
•  infection
•  musculoskeletal pain
•  nausea
•  nocturia

Mechanism of Action

• Nogapendekin alfa is a human interleukin (IL)-15N72D variant that is bound to inbakicept, a dimeric human IL-15R alpha sushi domain/human IgG1 Fc fusion protein; the nogapendekin alfa inbakicept complex acts as an IL-15 receptor agonist.
• IL-15 signals through a heterotrimeric receptor that is composed of the common gamma chain subunit, the beta chain subunit, and the alpha subunit which is specific to IL-15. IL-15 is trans-presented by the IL-15 receptor alpha to the shared IL-2/IL-15 receptors (beta chain and gamma chain) on the surface of CD4 and CD8 T cells and NK cells.
• Binding of these receptors results in proliferation and activation of NK, CD8, and memory T cells without proliferation of immunosuppressive T-reg cells.

In a carcinogen-induced model of bladder cancer in immunocompetent rats, intravesicular administration of nogapendekin alfa inbakicept either alone or in combination with BCG showed anti-tumor activity when compared to BCG alone.⁷⁰⁵⁴³

Pharmacokinetics

•Route-Specific Pharmacokinetics

Other Route(s)

Following intravesical administration at the recommended dose, the systemic exposure of nogapendekin alfa inbakicept was below the lower limit of quantification (100 pg/mL) in all patients.⁷⁰⁵⁴³

Monitoring Parameters

•  pregnancy testing

Classifications

• Antineoplastic and Immunomodulating Agents
  • Immunostimulating Agents
    • Interleukins

References

70543.Anktiva (nogapendekin alfa inbakicept-pmln) solution package insert. Bothell, WA; Altor BioScience, LLC: 2024 April.

70544.Chamie K, Chang SS, Kramolowsky E, et al. IL-15 Superagonist NAI in BCG-Unresponsive Non–Muscle-Invasive Bladder Cancer. NEJM Evid. 2022;2(1):1-11.