Nogapendekin alfa

Systemic exposure of nogapendekin alfa inbakicept-pmln following intravesical administration of 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 nogapendekin alfa inbakicept-pmln 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.

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 of the approved dosage of nogapendekin alfa inbakicept-pmln 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-pmln and any potential adverse effects on the breastfed child from nogapendekin alfa inbakicept-pmln or from the underlying maternal condition.

Carcinogenicity and genotoxicity studies have not been conducted with nogapendekin alfa inbakicept-pmln.

Fertility studies with nogapendekin alfa inbakicept-pmln have not been conducted.

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 nogapendekin alfa inbakicept-pmln 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. Patients received 400 mcg nogapendekin alfa inbakicept-pmln 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 nogapendekin alfa inbakicept-pmln with BCG administered to patients was 12 (range 2–30) doses. The median duration of exposure to nogapendekin alfa inbakicept-pmln with BCG was 7.1 months (range: 0.26 to 36.3 months).

Serious adverse reactions occurred in 16% of patients receiving nogapendekin alfa inbakicept-pmln with BCG. Serious adverse reactions that occurred in ≥2% of patients who received nogapendekin alfa inbakicept-pmln with BCG included hematuria (3.4%). A fatal adverse reaction of cardiac arrest occurred in 1 (1.1%) patient receiving nogapendekin alfa inbakicept-pmln with BCG.

Permanent discontinuation of nogapendekin alfa inbakicept-pmln with BCG due to adverse reactions occurred in 7% of patients. Adverse reactions (>2%) resulting in permanent discontinuation of nogapendekin alfa inbakicept-pmln with BCG included musculoskeletal pain (2.3%).

Dosage interruptions due to adverse reactions occurred in 34% of patients receiving nogapendekin alfa inbakicept-pmln with BCG. Adverse reactions (≥5%) that resulted in interruption of nogapendekin alfa inbakicept-pmln 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 nogapendekin alfa inbakicept-pmln; 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

Clinically relevant adverse reactions in <15% of patients who received nogapendekin alfa inbakicept-pmln 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 posttreatment value.