Nogapendekin Alfa Inbakicept-pmln Receives FDA Approval for BCG-Unresponsive Bladder Cancer

On April 22, 2024, the US Food and Drug Administration (FDA) approved a treatment with Bacillus Calmette-Guérin (BCG) for adults with BCG-unresponsive non-muscle-invasive bladder cancer: nogapendekin alfa inbakicept-pmln (Anktiva, Altor BioScience, LLC). This cancer may occur with carcinoma in situ (CIS) or with papillary tumors.

How Does Nogapendekin Alfa Inbakicept-pmln Work?

Nogapendekin alfa inbakicept-pmln, marketed as Anktiva, is a biological treatment. It is a genetically modified form using alfa inbakicept, a derivative of the cytokine interleukin-2 (IL-2). It is therefore a type of immunotherapy. IL-2 is a natural part of the immune system, promoting T-cell activation and proliferation to help the body use its own defenses against cancer cells.

Nogapendekin alfa inbakicept-pmln uses IL-2's immune-activating properties but is designed more specifically to target the tumor microenvironment and activate immune cells there. These cells specifically target and destroy tumor cells. Local administration, such as direct intravesical delivery into the bladder, enables a direct effect while reducing systemic adverse effects.

This specific, local approach offers an effective alternative particularly for BCG (Bacillus Calmette-Guérin)-unresponsive non-muscle-invasive bladder cancer. It harnesses the immune system's natural power to strengthen anticancer responses and suppress tumor growth.

The Study Supporting FDA Approval

Efficacy was evaluated in QUILT-3.032 (NCT0302285), a single-arm, multicenter study of 77 patients with BCG-unresponsive, high-risk non-muscle-invasive bladder cancer. Patients received BCG followed by nogapendekin alfa inbakicept-pmln induction and maintenance treatment continuing for up to 37 months.

Tumor status was assessed by mandatory biopsy within the first 6 months after treatment initiation and by cystoscopy and urine cytology every 3 months for 2 years after treatment.

Findings

• The complete response (CR) rate was 62% (95% CI: 51, 73).
• Among complete responders, duration of response (DOR) was ≥ 12 months in 58% and ≥ 24 months in 40%.

Adverse Events

The most common adverse events included increased creatinine, dysuria, hematuria, urinary frequency, urgency, urinary tract infection, increased potassium, musculoskeletal pain, chills and fever.

Recommended Dosing

For induction, the recommended dose is 400 mcg intravesically with BCG once weekly for 6 weeks. If CR is not achieved at month 3, a second induction course may be given. For maintenance, the recommended dose is 400 mcg intravesically with BCG once weekly for 3 weeks at months 4, 7, 10, 13 and 19.

Conclusion

FDA-approved nogapendekin alfa inbakicept-pmln offers a promising option in BCG-unresponsive non-muscle-invasive bladder cancer. Healthcare professionals considering this treatment should monitor patients carefully when deciding whether to continue.

*

FDA-Approved Treatments for BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer

• The QUILT-3.032 Study: Nogapendekin alfa inbakicept-pmln produced a complete response rate of 62%. Responses lasted at least 12 months in 58% and at least 24 months in 40%. Median DOR was not reported.
• The KEYNOTE-057 Study: FDA approval was granted in 2020. With pembrolizumab immunotherapy, 41% had a complete response, and 46% had responses lasting at least 12 months. Median DOR was 16.2 months.
• The Adstiladrin Study: FDA approval was granted in 2022. Complete responses occurred in 51%, with responses lasting at least 12 months in 46%. Median DOR was 9.7 months.