Nogapendekin alfa inbakicept-pmln, an interleukin-15 (IL-15) receptor agonist, is an antineoplastic agent.1
Nogapendekin alfa inbakicept-pmln is 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.1
The efficacy of nogapendekin alfa inbakicept-pmln was evaluated in QUILT-3.032, a single-arm, multicenter trial in adults with high-risk, BCG-unresponsive NMIBC with CIS, with or without Ta (noninvasive)/T1 (invasion into the lamina propria but not muscle) papillary disease, following transurethral resection (TUR).1, 2 BCG-unresponsive CIS was defined as persistent or recurrent CIS (alone or with Ta/T1 disease) occurring within 12 months after completion of adequate BCG therapy (i.e., administration of at least 5 of 6 induction doses plus either administration of at least 2 of 3 maintenance doses or at least 2 of 6 doses of a second induction course).1, 2 All patients with Ta/T1 disease underwent TUR to remove resectable disease.1, 2 Residual CIS not amenable to complete resection, fulguration, or cauterization was permitted.1, 2 Patients with muscle-invasive (T2-T4), locally advanced, metastatic, or extra-vesical bladder cancer were excluded.1, 2
Patients received intravesical nogapendekin alfa inbakicept-pmln 400 mcg with BCG 50 mg (consistent with the labeled intravesical dose) weekly for 6 weeks as induction therapy.1, 2 Those without high-grade recurrence continued with maintenance doses every 3 weeks at months 4, 7, 10, 13, and 19.1, 2 Patients with persistent CIS or high-grade Ta disease at 3 months were eligible for a second induction course.1, 2 Those with ongoing complete response (CR) at 25 months could receive additional instillations at months 25, 31, and 37.1 Tumor assessments were performed every 3 months for the first 2 years, including cystoscopy and urine cytology, and biopsies were required within the first 6 months.1, 2 Monitoring beyond 24 months was conducted per local practice standards.1, 2 Primary efficacy outcomes included CR at any time (defined by negative cystoscopy and urine cytology) and duration of response.1, 2
The efficacy population consisted of 77 patients.1, 5 The median age of these patients was 73 years (range 50-91); 86% were male, 90% were White, and 83% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0.1 At baseline, 69% of patients had CIS without papillary disease, 21% had CIS with Ta disease, and 10% had CIS with T1 ± Ta disease; 43% were classified as refractory and 57% as relapsed.1, 2 Patients had received a median of 12 prior BCG doses (range 8-45), with 13% receiving partial-dose BCG.1
A total of 48 patients (62%) achieved a complete response at any time during the study.1 Of the 77 patients evaluated, 31% received a second induction course.1 The median duration of response was 45.5 months, but this was considered to be an unreliable estimate due to several study limitations; therefore, a range of 0 to 47+ months was reported for duration of response.1, 5 Among the 48 patients who achieved a complete response, 58% had a duration of response ≥12 months and 40% had a duration of response ≥24 months.1 Patient-reported health-related quality of life outcomes showed a modest decrease in global health and physical function scores, with less of a decrease among responders (those with a complete response) than nonresponders.2
Non-muscle invasive bladder cancer (NMIBC; previously referred to as superficial bladder cancer) represents approximately 75% of newly diagnosed bladder tumors and is usually treated initially with surgical resection and/or fulguration.4 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 carcinoma in situ (stage Tis).4 Risk stratification is recommended in patients with NMIBC to guide treatment decisions.4 At the time of each occurrence or recurrence, patients should be assigned a clinical stage and classified as "low-", "intermediate-", or "high-risk".4
Following transurethral resection (TUR) of the bladder tumor, intravesical BCG immunotherapy is the standard of care for patients with high risk of recurrence of NMIBC.2, 4 Current guidelines from the American Urological Association and Society of Urologic Oncology (AUA/SUO) recommend a 6-week induction course of BCG for patients with newly diagnosed CIS, high-grade T1, or high-risk Ta disease.2, 4 Despite the efficacy of BCG, up to 40-50% of patients fail initial therapy or experience disease recurrence.2, 4
The International Bladder Cancer Group recommends the use of nogapendekin alfa inbakicept-pmln plus BCG as a bladder-sparing option for patients with BCG-unresponsive CIS and supports its use in patients with high-grade papillary disease, contingent on BCG availability.3 Without effective treatment, high-risk NMIBC carries a significant risk of progression to muscle-invasive bladder cancer or metastatic disease.1, 3
Administer nogapendekin alfa inbakicept-pmln by intravesical instillation into the bladder.1 Do not administer by the subcutaneous, IV, or IM routes.1
Must be administered with BCG and diluted before administration.1
Nogapendekin alfa inbakicept-pmln is available as a 400 mcg/0.4 mL solution in single-dose vials.1
Store vials under refrigeration at 2-8°C in the original carton to protect from light.1 Do not freeze.1 Do not shake.1
Prior to administration, inspect the nogapendekin alfa inbakicept-pmln vial for particulate matter and discoloration; discard the vial if observed.1 Prepare the BCG saline suspension according to the BCG prescribing information.1 Using aseptic technique, withdraw 0.4 mL of nogapendekin alfa inbakicept-pmln into a small syringe and add it to the prepared BCG saline suspension.1 Gently mix the suspension.1 Then, using a 60-mL syringe with an appropriate needle, withdraw the nogapendekin alfa inbakicept-pmln and BCG admixture to a total volume of 50 mL.1 If not used immediately, store the admixture under refrigeration at 2-8°C and use within 2 hours; discard any unused solution after that time.1
Instill the admixture of nogapendekin alfa inbakicept-pmln and BCG into the bladder using a catheter, and remove the catheter after instillation.1 Patients should retain the solution in the bladder for 2 hours before voiding.1 If the patient cannot retain the admixture for the full 2 hours, the patient may void earlier.1 The dose should not be repeated if voiding occurs before 2 hours.1 Refer to the BCG prescribing information for additional details on bladder retention and patient positioning.1
The recommended adult dosage of nogapendekin alfa inbakicept-pmln for the treatment of BCG-unresponsive nonmuscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors is 400 mcg administered with BCG by intravesical installation once weekly for 6 weeks.1 If a complete response is not achieved by 3 months, a second induction course may be given.1
Following induction therapy with nogapendekin alfa inbakicept-pmln and BCG, the recommended maintenance dosage of nogapendekin alfa inbakicept-pmln is 400 mcg administered intravesically with BCG once weekly for 3 weeks at months 4, 7, 10, 13, and 19 (for a total of 15 doses).1 For patients who maintain complete response at month 25 and later, additional instillations of nogapendekin alfa inbakicept-pmln with BCG may be given once weekly for 3 weeks at months 25, 31, and 37, for up to 9 additional doses.1
Continue treatment until lack of response after the second induction course, disease recurrence or progression, unacceptable toxicity, or a maximum of 37 months.1
The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.1
The manufacturer makes no specific dosage recommendations for patients with renal impairment.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
Risk of Metastatic Bladder Cancer with Delayed Cystectomy
Delaying cystectomy in patients with Bacillus Calmette-Guérin (BCG) unresponsive carcinoma in situ (CIS) increases the risk of developing muscle-invasive or metastatic bladder cancer, which can be fatal.1 The longer cystectomy is postponed in the presence of persistent CIS, the greater the risk of disease progression.1
In the QUILT-3.032 study, 77 evaluable patients with BCG-unresponsive CIS were treated with nogapendekin alfa inbakicept-pmln plus BCG.1 Among these patients, 8 progressed to muscle-invasive bladder cancer (≥T2 disease), of which 7 progressed during the treatment period.1 The median time from persistent or recurrent CIS to progression to muscle-invasive disease was 107 days (range 0-210 days).1
If patients with CIS do not achieve a complete response after a second induction course of nogapendekin alfa inbakicept-pmln with BCG, cystectomy should be reconsidered.1
There is insufficient information to characterize the anti-drug antibody response to nogapendekin alfa inbakicept-pmln and the effects of such antibodies on the pharmacokinetics, pharmacodynamics, safety, or effectiveness of the drug.1
Systemic exposure of nogapendekin alfa inbakicept-pmln following intravesical administration at the approved dosage was below the limit of quantitation.1 Based on its mechanism of action, nogapendekin alfa inbakicept-pmln may cause fetal harm when administered to a pregnant woman if systemic exposure occurs.1 There are no available data on use of the drug in pregnant women to inform a drug-associated risk.1
Advise pregnant women and females of reproductive potential of the potential risk to a fetus.1
There are no data on the presence of nogapendekin alfa inbakicept-pmln in human milk, its effects on the breastfed child, or on milk production.1 Systemic exposure following intravesical administration at the approved dose was below the limit of quantitation, suggesting any drug in milk would be low.1
Weigh the benefits of breastfeeding against the mother's clinical need for treatment and the potential risks to the child.1
Females and Males of Reproductive Potential
Based on its mechanism of action, nogapendekin alfa inbakicept-pmln may cause fetal harm if administered during pregnancy.1 Verify pregnancy status before starting treatment and advise females of reproductive potential to use effective contraception during therapy and for 1 week after the last dose.1
Safety and effectiveness of nogapendekin alfa inbakicept-pmln in pediatric patients have not been established.1
In clinical studies of nogapendekin alfa inbakicept-pmln for BCG-unresponsive NMIBC, 84% of patients were ≥65 years of age and 40% were ≥75 years of age.1 There were insufficient younger adults to assess differences in response by age.1
The most common (≥15%) adverse reactions, including laboratory test abnormalities, reported with nogapendekin alfa inbakicept-pmln are increased creatinine, dysuria, hematuria, urinary frequency, micturition urgency, urinary tract infection, increased potassium, musculoskeletal pain, chills, and pyrexia.1
Nogapendekin alfa inbakicept-pmln is an IL-15 receptor agonist.1 IL-15 activates immune cells by binding to a receptor consisting of 3 parts: the common gamma chain (γc), the beta chain (βc), and the IL-15-specific alpha subunit (IL-15Rα).1 The IL-15Rα presents IL-15 to the shared IL-2/IL-15 receptor (βc and γc) on CD4+ and CD8+ T cells, as well as natural killer (NK) cells.1 Binding of nogapendekin alfa inbakicept activates and expands NK cells, CD8+ T cells, and memory T cells without promoting regulatory T cell proliferation.1 In vivo, intravesical nogapendekin alfa inbakicept-pmln alone or with BCG demonstrated greater anti-tumor activity than BCG alone in an immunocompetent rat model of bladder cancer.1 Nogapendekin alfa inbakicept-pmln is produced using engineered Chinese Hamster Ovary-K1 cells and consists of the soluble nogapendekin alfa protein complex (a human IL-15N72D variant) bound to inbakicept (a dimeric human IL-15Rα sushi domain/human IgG1 Fc fusion protein).1
Patients who receive the approved dosage of nogapendekin alfa inbakicept-pmln by intravesical installation do not appear to exhibit quantifiable systemic exposure to the drug.1
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.
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]).
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Intravesical | Solution, for intravesical use | 400 mcg/0.4 mL | Anktiva® | Altor BioScience |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions August 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Altor BioScience, LLC, an indirect wholly-owned subsidiary of ImmunityBio, Inc. ANKTIVA® (nogapendekin alfa inbakicept-pmln) INTRAVESICAL prescribing information. 2024 Apr. [Web]
2. Chamie K, Chang SS, Kramolowsky EV, et al. Quality of life in the Phase 2/3 trial of N-803 plus Bacillus Calmette-Guérin in Bacillus Calmette-Guérin-unresponsive nonmuscle-invasive bladder cancer. Urol Pract. 2024;11(2):367-375.
3. Li R, Hensley PJ, Gupta S, et al. Bladder-sparing therapy for Bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer: International bladder cancer group recommendations for optimal sequencing and patient selection. Eur Urol. 2024;86(6):516-527.
4. Holzbeierlein JM, Bixler BR, Buckley DI, et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO Guideline: 2024 Amendment [published correction appears in J Urol. 2024 Dec;212(6):936. doi: 10.1097/JU.0000000000004251.]. J Urol. 2024;211(4):533-538.
5. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 761336Orig1s000: Multi-discipline review.