ImmunityBio, Inc. (NASDAQ: IBRX) has announced that the European Medicines Agency (EMA) has accepted for review its marketing authorization application (MAA) for ANKTIVA (nogapendekin alfa inbakicept-pmln) in combination with Bacillus Calmette-Guérin (BCG) for the treatment of patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors. The EMA's decision marks a significant step toward potentially expanding the availability of this immunotherapy to patients across the European Union, Iceland, Norway, and Liechtenstein.
The MAA is based on data from the ongoing QUILT 3.032 study, a single-arm, multicenter trial evaluating the safety and efficacy of ANKTIVA plus BCG in patients with BCG-unresponsive NMIBC CIS. As of the July 15, 2024, data cutoff, the study demonstrated a 71% complete response (CR) rate among 100 evaluable patients in Cohort A. Notably, in these responders, the duration of response ranged from 0.03 to 54 months and was ongoing, exceeding the benchmark of 18 months for clinically meaningful results suggested by the International Bladder Cancer Group.
Durable Responses Observed with ANKTIVA
The QUILT 3.032 study's findings, including the 71% complete response rate and the extended duration of response, align with previous data published in the New England Journal of Medicine. These results underscore ANKTIVA's potential to provide durable responses in patients with limited treatment options. The consistency between this expanded cohort and earlier data strengthens the reliability of these results.
"We are encouraged by the speed in which the EMA accepted our marketing authorization application and determined it would begin its assessment of our innovative treatment for this serious condition, just nine months after it was first approved by the FDA for use in the United States," said Dr. Patrick Soon-Shiong, Founder, Executive Chairman and Global Chief Scientific and Medical Officer of ImmunityBio.
Mechanism of Action
ANKTIVA is a first-in-class IL-15 agonist IgG1 fusion complex, consisting of an IL-15 mutant (IL-15N72D) fused with an IL-15 receptor alpha. This complex binds with high affinity to IL-15 receptors on NK, CD4+, and CD8+ T cells, mimicking the natural biological properties of the membrane-bound IL-15 receptor alpha. By activating NK cells, ANKTIVA overcomes the tumor escape phase of clones resistant to T cells and restores memory T cell activity with resultant prolonged duration of complete response.
Implications for Bladder Cancer Treatment
Bladder cancer is a significant global health concern, with NMIBC representing a substantial proportion of cases. BCG immunotherapy is a standard treatment for NMIBC, but many patients become unresponsive to it, creating an unmet medical need. ANKTIVA, in combination with BCG, offers a potential new treatment option for these patients, with the goal of improving outcomes and reducing the need for cystectomy (surgical bladder removal).
With the EMA's acceptance of the MAA, ANKTIVA is one step closer to becoming available to patients with BCG-unresponsive NMIBC in Europe. The ongoing QUILT 3.032 study continues to monitor patients to assess the durability of responses and overall survival outcomes.
