Nogapendekin Alfa Inbakicept Plus BCG Meets Primary End Point, sBLA Planned by Year-End

Adding intravesical nogapendekin alfa inbakicept-pmln (Anktiva; ImmunityBio) to Bacillus Calmette-Guérin (BCG) produced a statistically significant improvement in efficacy compared with BCG alone in patients with BCG-naïve, high-grade NMIBC with carcinoma in situ (CIS), with or without papillary tumors. The data comes from the final analysis of the primary end point in Cohort A of the randomized, controlled, registrational QUILT-2.005 trial (NCT02138734).¹

ImmunityBio did not disclose response rates, hazard ratios, or P values in its announcement; additional study details are expected at an upcoming medical congress. The company reported that patient-reported quality of life was maintained and that median duration of response had not yet been reached in the combination arm.¹

If the data hold up, the regimen would be the first chemotherapy-free immunotherapy given directly into the bladder alongside BCG in the BCG-naïve setting—moving an agent currently reserved for BCG-unresponsive disease up to the point of first treatment. ImmunityBio plans to submit a supplemental Biologics License Application to the FDA by the end of 2026.¹

Trial Design

QUILT-2.005 randomly assigned 370 patients receiving BCG-based therapy for the first time to intravesical nogapendekin alfa inbakicept plus BCG or BCG alone across more than 75 sites.

Christopher Pieczonka, MD, corporate director of clinical research at US Urology Partners and global principal investigator of QUILT-2.005, said frontline innovation in high-risk NMIBC has been limited, and he characterized the improved response rates in patients with CIS as "an important practice-changing advance." He added that improving responses earlier in the disease course could help more patients stay disease-free longer and avoid additional treatment.¹

Einar F. Sverrisson, MD, a urologist at Dartmouth Hitchcock Medical Center, noted that recurrence after standard-of-care BCG remains a significant challenge and that the study was built to test whether adding the IL-15 agonist could raise response rates and reduce the risk of early recurrence.¹

Safety

The most common treatment-emergent and treatment-related adverse events with the combination were consistent with those seen with BCG alone, and no treatment-related deaths were reported.¹

Mechanism and Regulatory History

Nogapendekin alfa inbakicept is a first-in-class IL-15 receptor agonist IgG1 fusion complex that combines an IL-15 mutant (IL-15N72D) with IL-15 receptor alpha. It binds IL-15 receptors on natural killer (NK), CD4+, and CD8+ T cells, driving NK-cell activation and proliferation and the generation of memory T cells.¹

The FDA first approved the agent with BCG in April 2024 for BCG-unresponsive NMIBC CIS with or without papillary disease. In October 2026, the indication was expanded to BCG-unresponsive NMIBC, including both CIS and papillary disease.¹

What Pharmacists Should Watch

An earlier-line indication would put nogapendekin alfa inbakicept in front of a much larger patient population—and onto the desks of pharmacists who handle intravesical therapy preparation, BCG supply planning, and patient counseling. Several points from the current labeling carry over directly:¹

• Route. The product is for intravesical use only and must not be given subcutaneously or intravenously.
• Adverse reactions. In the approved BCG-unresponsive setting, the most common adverse reactions (15% or more), including laboratory abnormalities, are increased creatinine, dysuria, hematuria, urinary frequency, micturition urgency, urinary tract infection, increased potassium, musculoskeletal pain, chills, and pyrexia. Counseling on expected irritative voiding symptoms vs signs of infection remains central.
• Reproductive risk. The agent may cause fetal harm; females of reproductive potential should be advised to use effective contraception.
• BCG dependence. Because the regimen is given with BCG, a frontline indication would add pressure to an already constrained BCG supply—a manufacturing and supply risk the company itself flags.

The full congress presentation will be the real test. Until response rates, durability, and the CIS vs papillary breakdown are public—and the open-label design is weighed against them—the headline result is a signal, not yet a practice change.

REFERENCE

ImmunityBio announces ANKTIVA plus BCG meets primary endpoint in BCG-naïve non-muscle invasive bladder cancer randomized QUILT-2.005 trial. News release. ImmunityBio. November 9, 2026. Accessed November 10, 2026. https://ir.immunitybio.com/news-releases/news-release-details/immunitybio-announces-anktivar-plus-bcg-meets-primary-endpoint