On February 5, 2024 ImmunityBio, Inc. (NASDAQ: IBRX), a clinical-stage immunotherapy company, reported that findings from Patient-Reported Outcomes (PROs) of participants in the phase 2/3 QUILT 3.032 study of N-803 plus BCG in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) were published by the peer-reviewed journal Urology Practice (Press release, ImmunityBio, FEB 5, 2024, View Source [SID1234639844]). These PROs support the positive interim results from the study published in NEJM Evidence, wherein 71% of patients in cohort A with CIS with or without Ta/T1 disease achieved a complete response.

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The published PROs based on a May 16, 2022 data cutoff indicate that both physical function and global health as self-reported by QUILT 3.032 participants with BCG-unresponsive NMIBC CIS (cohort A) or papillary disease (cohort B), remained stable over the 2-year course of the study for patients who completed the PRO questionnaires and reached 24 months on-study. In addition, overall both cohort A and B participants who reached month 24 on-study and also completed an NMIBC-specific questionnaire focusing on the challenges of bladder cancer, also reported no decline of their health or urinary tract-related symptoms while in the study. Overall, participants who achieved a complete response with the novel combination therapy reported better physical function by month six of the study than those who did not achieve a complete response.

"The self-reported stability of health and physical function over the course of the study by the participants reflect another aspect of safety and tolerability of this new combination therapy," said Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio. "Taken together with the positive response rate in cohort A of over 70%, the persistence of responses and cystectomy avoidance, these QoL findings suggest a favorable risk-benefit ratio for this potential new therapeutic option for patients with BCG-unresponsive bladder cancer."

The finding of relative stability of global health and physical function during the course of the study is similar to that reported by others for BCG monotherapy, suggesting the novel combination is as tolerable as treatment with BCG alone.

"Many current therapies for bladder cancer slow disease progression but can cause debilitating side effects," said Principal Investigator Karim Chamie, M.D., Associate Professor of Urology at UCLA. "The data from the QUILT 3.032 Quality of Life study suggest that many patients not only have a durable response but also report no decline in physical function, which is very important for these patients."

QUILT 3.032 Study Details

The ongoing phase 2/3 open-label multicenter registrational study QUILT 3.032 (NCT03022825) is evaluating the safety and efficacy of the investigational interleukin-15 superagonist N-803 (also known as Anktiva and nogapendekin alfa inbakicept, NAI) in combination with a standard therapy for NMIBC, bacillus Calmette-Guerin (BCG), in patients who failed or in whom cancer returned after BCG monotherapy, and thus were diagnosed as BCG-unresponsive. The study comprises three cohorts, with cohort A enrolling patients with carcinoma in situ (CIS) with or without Ta/T1 disease and cohort B enrolling patients with high grade Ta/T1 papillary disease. Both cohorts A and B received combination N-803 plus BCG therapy. Cohort C patients, with CIS +/- Ta/T1 disease received N-803 monotherapy.

The primary end point is the incidence of CR at the 3- or 6-month assessment visit for cohorts A and C, and the disease-free survival (DFS) rate at 12 months for cohort B.
Durability, cystectomy avoidance, progression-free survival, disease-specific survival (DSS), and overall survival are secondary end points for cohort A.
Cohort C was discontinued due to a low response rate with N-803 monotherapy, per study design.
The FDA has accepted for review ImmunityBio’s resubmission of its biologics license application (BLA) for N-803 plus BCG for the treatment of BCG-unresponsive NMIBC CIS with or without Ta or T1 disease, and has set a user fee goal date (PDUFA date) of April 23, 2024.
Bladder cancer is the 10th most-commonly diagnosed cancer, with approximately 80% of newly diagnosed cases being NMIBC. Intravesical (directly to the bladder) instillation of BCG after removal of cancer tissue from the lining of the bladder (transurethral resection of the bladder tumor; TURBT) is Standard-of-Care (SoC) for intermediate and high-risk NMIBC patients, but up to 40% of patients will fail BCG therapy and ~50% will relapse after an initial response and given a diagnosis of being BCG-unresponsive. Therapies approved by the FDA for this indication include pembrolizumab, nadofaragene, combined gemcitabine and docetaxel, and valrubicin. Radical cystectomy – surgical removal of the bladder – is also an option for these patients. QUILT 3.032 is being conducted to address the need for a safe, effective therapeutic option for BCG-unresponsive NMIBC patients that provides an opportunity for avoidance of radical cystectomy.

N-803 is investigational. Safety and efficacy have not been established by any Health Authority or Agency, including the FDA.