N-803 Plus Intravesical BCG Produces 57% DFS in BCG-Unresponsive Papillary Bladder Cancer


Intravesical Bacillus Calmette–Guérin in combination with N-803 resulted in a 12-month disease-free survival rate of 57% in patients with BCG-unresponsive high-grade papillary non–muscle invasive bladder cancer, meeting the primary end point for cohort B of the phase 2/3 QUILT 3.032 trial.

Patrick Soon-Shiong, MD

Patrick Soon-Shiong, MD

Intravesical Bacillus Calmette–Guérin (BCG) in combination with N-803 (Anktiva) resulted in a 12-month disease-free survival (DFS) rate of 57% in patients with BCG-unresponsive high-grade papillary non–muscle invasive bladder cancer (NMIBC), meeting the primary end point for cohort B of the phase 2/3 QUILT 3.032 trial (NCT03022825).1

At a median follow-up of 17.3 months, the DFS rate at 12 months was 57% (95% CI, 43.7%-68.5%) among the 73 patients with papillary disease who were enrolled to cohort B. The 18-month DFS rate in this population was 53.0% (95% CI, 38.8%-64.6%) per Kaplan-Meier analysis. Notably, durable responses were observed, and 85% of patients were significantly able to avoid cystectomy with this approach.

Regarding safety, the profile of N-803 proved to align with what has previously been reported in cohort A of the trial. No serious adverse effects (SAEs), including immune-related effects, were observed.

Full safety and efficacy data for cohorts A and B of the trial have been submitted for presentation at the 2022 Genitourinary Cancers Symposium, according to ImmunityBio, Inc.

“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 and executive chairman and global chief scientific and medical officer of ImmunityBio, Inc., stated in a press release. “[N-803] has demonstrated strong disease control in carcinoma in situ [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.”

The open-label, 3-cohort, multicenter trial enrolled patients with unresponsive, high-grade NMIBC who were 18 years of age or older, had histologically confirmed presence of BCG-unresponsive CIS or BCG-unresponsive high-grade Ta or T1 disease, and an ECOG performance status ranging from 0 to 2.2 Participants needed to have absence of resectable disease after transurethral resection procedures, and those with high-grade Ta and/or T1 disease should have undergone complete resection before treatment.

Patients were administered weekly N-803 plus BCG through a urinary catheter in the bladder for the duration of 6 consecutive weeks during the initial induction period. After the first disease assessment was conducted, patients received either a 3-week maintenance course or a 6-week reinduction course, which served as the second treatment period, at month 3. In the third period, patients who were determined to be eligible went on to receive maintenance treatment at 6, 9, 12, and 18 months of the 24-month study.

The primary end point of cohorts A and C were complete response (CR) and DFS. Secondary end points were duration of CR in cohorts A and C, and DFS in cohort B.

A total of 81 patients with histologically confirmed BCG-unresponsive NMIBC, with persistent or recurrent CIS within 12 months of receiving adequate BCG treatment, were enrolled to cohort A of the trial.3 Participants received 50 mg of BCG plus 400 mg of intravesical N-803 on a weekly basis for 6 weeks; this was followed by re-induction and maintenance for up to 3 years.

This cohort was comprised of heavily pretreated patients with a median of 5.0 transurethral resections of a bladder tumor, and median of 12.0 prior BCG instillations. Forty-two percent of patients previously received chemotherapy and 17% had prior checkpoint inhibitors, Vicinium, interferon, etc.

Findings presented during the 2021 American Urological Association Annual Meeting showed that the approach resulted in a CR rate of 72% (95% CI, 61%-81%), and a 58.6% (95% CI, 43.1%-71.2%) probability of maintaining a CR for at least 12 months. Moreover, at a median follow-up of 20.4 months, the median duration of CR was 19.9 months (95% CI, 7.8–not reached).

Among those who experienced an initial CR at 3 months, a 64% (95% CI, 47.3%-77.3%) probability of maintaining that response at 12 months was reported; the probability of maintaining the response at 18 months was 61% (95% CI, 43.2%-74.5%).

The regimen resulted in a durable response rate of 30% at 18 months, and 85% of patients had not progressed to radical cystectomy.

The combination was found to be well tolerated. No treatment-related SAEs, immune-related toxicities, or grade 4 or 5 treatment-related AEs were reported. Two patients experienced grade 3 TRAEs, which were urinary tract infection and arthralgia. The most common AEs that were grade 1 or 2 in severity included dysuria (22%), hematuria (16%), and pollakiuria (19%).

The US Patent & Trademark Office has permitted that the patent application for the use of N-803 in combination with BCG be extended to at least 2035.


  1. ImmunityBio announces primary endpoint met in a second indication in bladder cancer trial with 57% disease-free survival in patients with BCG unresponsive papillary disease. News release. October 19, 2021. Accessed October 20, 2021. https://yhoo.it/3vuqrCg
  2. QUILT-3.032: a multicenter clinical trial of intravesical Bacillus Calmette-Guerin (BCG) in combination with ALT-803 in patients with BCG unresponsive high grade non-muscle invasive bladder cancer. ClinicalTrials.gov. Updated December 22, 2020. Accessed December 22, 2020. https://clinicaltrials.gov/ct2/show/NCT03022825
  3. Chamie K, Chang S, Gonzalgo M, et al. Phase 2/3 clinical results of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) carcinoma in-situ (CIS) patients (cohort A). Presented at: 2021 American Urological Association Annual Meeting; September 10-13, 2021; virtual. Abstract PD09-05.
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