Nogapendekin Alfa Inbakicept-Pmln

Description

11 DESCRIPTION Nogapendekin alfa inbakicept-pmln is an interleukin-15 (IL-15) receptor agonist. It is a soluble complex consisting of (a) nogapendekin alfa (a human IL-15N72D variant, 114 amino acids) bound to (b) inbakicept [a dimeric human IL-15Rα sushi domain (65 amino acids)/human IgG1 Fc fusion protein (232 amino acids)]. Each fully assembled nogapendekin alfa inbakicept-pmln complex consists of a single inbakicept and two nogapendekin alfa components. Each IL-15N72D component is bound to one of the IL-15Rα sushi domains. The recombinant protein complex is produced by a recombinant cell line that was created by transfecting a Chinese hamster ovary (CHO-K1) cell line with plasmids carrying genes for the IL-15N72D and IL-15RαSu/IgG1 Fc proteins. Purification of the product is achieved by conventional chromatography. The molecular weight of the deglycosylated nogapendekin alfa inbakicept-pmln complex is 92,106.5 Da. The molecular weights of the individual deglycosylated sub-units are 66565.6 Da (dimer) and 12,770.45 Da for the IL-15RαSu/IgG1 Fc domain and the IL-15N72D domain, respectively. ANKTIVA (nogapendekin alfa inbakicept-pmln) solution is a clear to slightly opalescent, colorless to slightly yellow solution provided in a single-dose vial containing 400 mcg in 0.4 mL for intravesical administration upon dilution [see Dosage and Administration ( 2 )] . Each vial also contains dibasic sodium phosphate (0.57 mg), monobasic potassium phosphate (0.54 mg), sodium chloride (3.27 mg) and Water for Injection, USP. Hydrochloric acid and sodium hydroxide is added to adjust the pH to 7.4.

What Is Nogapendekin Alfa Inbakicept-Pmln Used For?

1 INDICATIONS AND USAGE 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. ANKTIVA is an interleukin-15 (IL-15) receptor agonist indicated 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 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION For Intravesical Use Only 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 ) 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 ) Instill intravesically only after dilution. Total time from vial puncture to the completion of the intravesical instillation should not exceed 2 hours. ( 2.2 ) See full Prescribing Information for dilution and administration instructions. 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. 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...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS 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. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Altor BioScience, LLC, an indirect wholly-owned subsidiary of ImmunityBio, Inc. at toll-free phone 877-265-8482 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of ANKTIVA with BCG was evaluated in Cohort A of QUILT-3.032, a single-arm, multicenter clinical study in 88 patients with BCG-unresponsive high-grade NMIBC with CIS with or without Ta/T1 papillary disease [see Clinical Studies ( 14 )]. Patients received 400 mcg ANKTIVA with BCG weekly for 6 consecutive weeks during induction and then once a week for every 3 weeks at 4, 7, 10, 13, and 19 months for patients with no or low grade disease. Patients with persistent CIS or high grade Ta at 3 months were eligible to receive a second induction. Patients with ongoing CR at 25 months were eligible to receive additional instillations once a week every 3 weeks at months 25, 31, and 37. The median number of doses of ANKTIVA with BCG administered to patients was 12 (range 2 – 30) doses. The median duration of exposure to ANKTIVA with BCG was 7.1 months (range: 0.26 to 36.3 months). Serious adverse reactions occurred in 16% of patients receiving ANKTIVA with BCG. Serious adverse reactions that occurred in ≥2% of patients who received ANKTIVA with BCG included hematuria (3.4%). A fatal adverse reaction of cardiac arrest occurred in 1 (1.1%) patient receiving ANKTIVA with BCG. Permanent discontinuation of ANKTIVA with BCG due to adverse reactions occurred in 7% of patients. Adverse reactions (>2%) resulting in permanent discontinuation of ANKTIVA with BCG included musculoskeletal pain (2.3%). Dosage interruptions due to adverse reactions occurred in 34% of patients receiving ANKTIVA with BCG. Adverse reactions (≥5%) that resulted in interruption of ANKTIVA with BCG were urinary tract infection (10%), dysuria (8%), hematuria (6%), and bladder irritation (6%). Dosage reductions due to adverse reactions were not permitted for ANKTIVA; however, dose reduction of BCG was allowed for adverse reactions and occurred in 3.4% of patients including (>1%) urinary tract infection (2.3%), hematuria (1.1%), urinary frequency (1.1%), and bladder irritation (1.1%). The most common (≥15%) adverse reactions, including laboratory test abnormalities, were increased creatinine, dysuria, hematuria, urinary frequency, micturition urgency, urinary tract infection, increased potassium, musculoskeletal pain, chills and pyrexia. Table 1 summarizes the adverse reactions in Cohort A of QUILT-3.032. Table 1: Adverse Reactions Occurring in ≥15% of Patients in Cohort A in QUILT-3.032 1 Includes other related terms Adverse Reaction ANKTIVA with BCG (n=88) All Grades % Grades 3 or 4 % Dysuria 32 0 Hematuria 1 32 3.4 Urinary Frequency 27 0 Micturition Urgency 1 25 0 Urinary Tract Infection 1 24 2.3 Musculoskeletal Pain 1 17 2.3 Chills 15 0 Pyrexia 15 0 Clinically relevant adverse reactions in <15% of patients who received ANKTIVA with BCG included fatigue (14%), nausea (14%), bladder irritation (11%), diarrhea (9%), and nocturia (7%). Table 2 summarizes the laboratory test abnormalities occuring in ≥15% of patients in QUILT-3.032. Table 2: Select Laboratory Test Abnormalities (≥15%) That Worsened From Baseline in Patients in Cohort A of QUILT-3.032 1 The denominator used to calculate the rates was 88 based on the number of patients with a baseline value and at least one post-treatment value....

Contraindications

4 CONTRAINDICATIONS None None ( 4 )

Pregnancy and Breastfeeding

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 ( 12.1 )] . 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.

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 ( 8.1 )] . 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.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING ANKTIVA (nogapendekin alfa inbakicept-pmln) is clear to slightly opalescent and colorless to slightly yellow solution available in: Carton containing 400 mcg/0.4 mL, single-dose vial (NDC 81481-803-01). Store vials under refrigeration at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Do not shake.