Intravesical BCG Plus Novel IL-15 Superagonist Complex Improves DFS in BCG-Unresponsive Non-Muscle Invasive Bladder Cancer

Patients with Bacillus Calmette-Guerin–unresponsive non-muscle invasive bladder cancer experienced a disease-free survival benefit when treated with intravesical Bacillus Calmette-Guerin and a novel IL-15 superagonist complex .

Treatment with intravesical Bacillus Calmette-Guerin (BCG) and a novel IL-15 superagonist complex (Anktiva; N-803) resulted in a promising disease-free survival (DFS) rate in a population of patients with BCG-unresponsive, papillary non-muscle invasive bladder cancer (NMIBC), according to findings from the phase 2/3 QUILT-3.032 study (NCT03022825).

Findings from the study indicated that the primary end points of complete response rate for cohort A (n = 81), which included patients with carcinoma in situ (CIT), and DFS rate for cohort B with papillary disease (n = 73) were met in both. Those with papillary disease had a 12-month DFS rate of 57% (95% CI, 43.7%-68.5%) and an 18-month rate of 53% (95% CI, 38.8%-64.6%). Additionally, the CIT cohort had a complete response rate of 72%. Notably, a new patent for intravesical use of N-803/BCG for patients with bladder was extended until 2035 at a minimum.

“Intravesical BCG has been the standard of care for more than 30 years for patients with non-invasive papillary tumors, yet, unfortunately some 40% of them don’t respond,” Patrick Soon-Shiong, MD, founder, executive chairman, and global chief Scientific and medical officer at ImmunityBio, said in a press release. “Anktiva has demonstrated strong disease control in CIS, and based on the latest data from our study, it is showing the same effect in papillary tumors. This gives us confidence in the potential for all BCG-unresponsive NMIBC patients to benefit from this combination therapeutic.”

IL-15 stimulates CD8-positive T cells and natural killer cells via its b-g T-cell receptor binding in addition to avoiding T-reg stimulation. N-803 had been observed to improve pharmacokinetic characteristics, yield a longer persistence in lymphoid tissues, and boost antitumor activity vs noncomplexed IL-15 in vivo.

A total of 154 patients were included in the study, 73 of whom were enrolled into cohort B with a median follow up of 17.3 months. Additionally, treatment with BCG and N-803 resulted in durable responses within both cohorts and significantly helped patients to avoid cystectomy (85%).

Safety signals related to N-803 within cohort B were consistent with what was previously seen in cohort A. This included no serious adverse effects (SAEs) or immune-related SAEs. Investigators reported that a full safety and efficacy analysis from both cohorts had been submitted to the American Society of Clinical Oncology Genitourinary Cancer Symposium for February 2022.

The FDA granted the treatment a fast track designation based on data from the pivotal phase 1 trial, as well as breakthrough therapy designation in 2019 based on the interim phase 2 findings, which indicated that the trial’s primary end point had already been met.


ImmunityBio announces primary endpoint ket in a second indication in bladder cancer trial with 57% disease-free survival in patients with BCG unresponsive papillary disease. News release. ImmunityBio Inc. October 19, 2021. Accessed October 20, 2021.