Nogapendekin Alfa Inbakicept-pmln Approved for BCG-Unresponsive Non–Muscle-Invasive Bladder Cancer

The FDA has granted approval to nogapendekin alfa inbakicept-pmln (Anktiva®, Altor BioScience, LLC) with Bacillus Calmette-Guérin (BCG) for adult patients with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors.  

Why it matters: “Patients with BCG-unresponsive NMIBC have limited treatment options,” wrote Karim Chamie, MD, an Associate Professor of Urology at the University of California, Los Angeles (UCLA), and colleagues, in their published results of the QUILT-3.032 trial (NCT0302285), on which approval was based. “The immune cell–activating interleukin-15 (IL-15) superagonist nogapendekin alfa inbakicept, also known as N-803, may act synergistically with BCG to elicit durable complete responses in this patient population.”

What they studied: Efficacy was measured in the phase 2/3, open-label, single-arm, multicenter trial which enrolled 77 patients with BCG-unresponsive, high-risk NMIBC with carcinoma in situ with or without Ta/T1 papillary disease following transurethral resection. Patients received 400 mcg of nogapendekin alfa inbakicept-pmln via intravesical instillation with BCG for six consecutive weeks during the induction treatment period, followed by maintenance therapy once a week every three weeks for up to 37 months.

The primary efficacy end points measured were complete response and duration of complete response. Tumor status was assessed via cystoscopy and urine cytology every three months for up to two years, with random or cystoscopy-directed biopsy required within the first six months of treatment. Local community standards were used for subsequent assessment.

What they found: Nogapendekin alfa inbakicept-pmln produced a complete response rate of 62%, with 58% achieving a duration of complete response ≥12 months and 40% achieving a duration of complete response ≥24 months.

Adverse events: The most common adverse events experienced by ≥15% of those receiving nogapendekin alfa inbakicept-pmln, including laboratory test abnormalities, were increased creatinine, dysuria, hematuria, urinary frequency, micturition urgency, urinary tract infection, increased potassium, musculoskeletal pain, chills, and pyrexia.

Conclusion: “In patients with BCG-unresponsive bladder carcinoma in situ and papillary NMIBC treated with BCG and the novel agent nogapendekin alfa inbakicept-pmln, complete responses were achieved with a persistence of effect, cystectomy avoidance, and 100% bladder cancer–specific survival at 24 months,” concluded Dr. Chamie and colleagues.

Instructions: The recommended dosage is 400 mcg of nogapendekin alfa inbakicept-pmln administered intravesically with BCG once a week for six weeks as induction therapy. If complete response is not achieved within three months, a second induction course may be administered. Following induction therapy, the recommended dosage during maintenance therapy is 400 mcg administered intravesically with BCG once a week for three weeks at Months 4, 7, 10, 13, and 19, for a total of 15 doses. Of those with an ongoing complete response at Month 25 or later, maintenance instillations with BCG may be administered once a week for three weeks at Months 25, 31, and 37 for a maximum of nine additional instillations. The maximum treatment duration is 37 months. Treatment should be discontinued for disease persistence after second induction, disease recurrence or progression, or unacceptable toxicity.

For More Information

Chamie K, Chang SS, Kramolowsky E, et al (2023). IL-15 superagonist NAI in BCG-unresponsive non-muscle-invasive bladder cancer. NEJM Evid, 2(1):EVIDoa2200167. DOI:10.1056/EVIDoa2200167

Clinicaltrials.gov (2024). QUILT-3.032: A multicenter clinical trial of intravesical Bacillus Calmette-Guerin (BCG) in combination with ALT-803 (N-803) in patients with BCG unresponsive high grade non-muscle invasive bladder cancer. NLM identifier: NCT03022825.

Anktiva® (nogapendekin alfa inbakicept-pmln) prescribing information (2024). Altor BioScience, LLC. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761336s000lbl.pdf

US Food and Drug Administration (2024). FDA approves nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nogapendekin-alfa-inbakicept-pmln-bcg-unresponsive-non-muscle-invasive-bladder-cancer

Image credit: Mikael Häggström. Licensed under CC0 1.0

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