ImmunityBio Announces Over 24 Months Median Duration of Complete Remission, with 100% NMIBC CIS Patient Survival, Setting a New ‘Magnitude of Benefit’ in Patients with BCG Unresponsive Bladder Cancer
ImmunityBio, Inc. (NASDAQ: IBRX) announced promising results from its late-stage bladder cancer trial (QUILT-3.032). Of the 83 patients with BCG-unresponsive non-muscle invasive carcinoma in situ (CIS), 71% achieved complete response, with a median response duration of 24.1 months, surpassing FDA-approved therapies like pembrolizumab (41%) and valrubicin (18%). The study showed over 90% cystectomy avoidance and a remarkable safety profile with no severe adverse events. This trial positions ImmunityBio's treatment as a potential new standard of care for bladder cancer patients.
- 71% complete response rate for patients with BCG-unresponsive NMIBC CIS.
- Median response duration of 24.1 months, exceeding historical rates.
- Over 90% cystectomy avoidance rate (91% for CIS and 95% for papillary disease).
- Zero treatment-related adverse events reported.
- None.
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Results confirm prolonged sustained complete response, with
71% of patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) carcinoma in situ (CIS) having a complete remission with a median duration of response of 24.1 months -
By contrast, historical complete response rates for FDA-approved therapies pembrolizumab and valrubicin are of
41% and18% , respectively1 & 2 -
In addition, for patients with papillary disease, a disease-free survival rate at 18 months of
53% , which more than doubles the25% rate published by theInternational Bladder Cancer Group as clinically meaningful -
A cystectomy avoidance rate of over
90% (91% of CIS patients and95% of papillary patients) -
A
96% avoidance rate of progression to muscle invasive bladder cancer for CIS patients who responded to therapy - Zero treatment-related or immune-related adverse events or grade 4/5 adverse events
“We are excited with these promising results,” said
The latest data from this trial exceeds AUA-FDA workshop benchmarks for both the magnitude of complete remission and the duration of complete response for new therapies for BCG-unresponsive bladder cancer. Indeed, the benchmark of
“Trained immunity is a recently discovered immune system response triggered by BCG. Natural Killer (NK) and T cells are activated by BCG resulting in bladder cancer cell death. When an appropriate secondary stimulus is administered along with BCG, that trained immune response is enhanced to induce immune memory resulting in a prolonged duration of immunological response,” said
“These results support our hypothesis that immunogenic cell death can induce long-term memory and that N-803 increases the immunologic potential of BCG, even in patients who become unresponsive to BCG alone,” Soon-Shiong said. “N-803 does this by stimulating proliferation and enhancing activity of tumor-killing Natural Killer (NK) cells and T cells, acting as a secondary stimulus or boost to the prime trained immunity induced by BCG.”
The study results presented at ASCO GU are summarized below:
Cohort A (CIS)
Excellent safety and tolerability profile of N-803 + BCG for CIS
-
0% treatment-related SAEs -
0% immune-related AE -
0% grade 4 and 5 AE
-
71% Complete remission (CR) rate at anytime - 24.1 Months median durable complete remission
-
96% Avoidance of bladder cancer progression at 24 months in responders -
91% Avoidance of cystectomy at 24 months in responders -
100% Bladder cancer specific overall survival at 24 months - Favorable & familiar dosing schedule with activity localized to the bladder
Cohort B (Papillary Disease)
Excellent safety and tolerability profile of N-803 + BCG for papillary disease
-
0% treatment-related SAEs -
0% immune-related AE -
0% grade 4 and 5 AE
-
57% Disease free survival rate at 12 months -
99% Overall bladder cancer specific survival -
95% Cystectomy avoidance rate - Favorable & familiar dosing schedule with activity localized to the bladder
“When we began the QUILT trials across multiple tumor types, initiating our Cancer Moonshot program, the goal was to achieve a new paradigm in cancer care by activating the patient’s own immune system to induce NK and T cell memory with long-term complete remission in patients who have failed all current therapies,” Soon-Shiong said. “With these results in bladder cancer, as well as our recently reported results in pancreatic cancer, we are one step closer to proving our hypothesis that delivering therapies that harness the patient’s own immune system is what will truly transform current standards of care.”
The data will be announced on
Incidence of Bladder Cancer
Bladder cancer has a high incidence worldwide; in 2020, an estimated 573,278 new cases were diagnosed and caused 212,536 deaths.4 In
For the last 30 years, BCG immunotherapy has been the standard for treating NMIBC. However, disease recurrence and progression rates remain unacceptably high. Standard-of-care recommendations include lifetime invasive surveillance and rapid treatment of recurrences, creating a substantial financial burden and drastic impact on quality of life. Of those patients who experience recurrence, approximately
There is an urgent, unmet need to treat NMIBC and avoid cystectomy. Despite the advent of minimally-invasive procedures and robotic techniques, the 90-day mortality and morbidity rates in cystectomy patients remain unacceptably high at 3
About the Study and Breakthrough Designation
QUILT 3.032 is an open-label, three cohort, multicenter Phase 2/3 study of intravesical BCG plus Anktiva (N-803) in patients with BCG-unresponsive high-grade NMIBC (NCT03022825) and was opened in 2017. The primary endpoint for Cohort A of this Phase 2/3 study is incidence of complete response (CR) of CIS at any time. The FDA had granted Fast Track Designation to the pivotal trial based on Phase I data. In
ImmunityBio’s IL-15 superagonist Anktiva (N-803)
The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of the natural killer (NK) and T cells. N-803 is a novel IL-15 superagonist complex consisting of an IL-15 mutant (IL-15N72D) bound to an IL-15 receptor α/IgG1 Fc fusion protein. Its mechanism of action is direct specific stimulation of CD8+ T cells and NK cells through beta gamma T-cell receptor binding (not alpha) while avoiding T-reg stimulation. N-803 has improved pharmacokinetic properties, longer persistence in lymphoid tissues and enhanced anti-tumor activity compared to native, non-complexed IL-15 in vivo.
N-803 is currently being evaluated for adult patients in two clinical NMIBC trials. QUILT 2.005 is investigating use of N-803 in combination with BCG for patients with BCG-naïve NMIBC; QUILT 3.032 is studying N-803 in combination with BCG in patients with BCG-unresponsive NMIBC.
Mechanism of Action & Contribution of N-803 (Anktiva) and BCG for Bladder Cancer
Trained immunity10 is a recently discovered immune system response triggered by BCG. Natural Killer (NK) and T cells11 are activated by BCG resulting in bladder cancer cell death. When an appropriate secondary stimulus is administered along with BCG, that trained immune response is enhanced to induce immune memory resulting in a prolonged duration12 of immunological response. N-803, an IL-15 superagonist which proliferates NK and T cells13, serves as this enhancing secondary boost and augments the immunological response when given in combination with BCG. This mechanism of action of inducing trained innate immune memory, through the combination of N-803 and BCG, accounts for the prolonged 24-month durable complete response reported in this trial.
About
ImmunityBio’s clinical pipeline consists of 21 clinical trials—13 of which are in Phase II or III development—across 12 indications in solid and liquid cancers (including bladder, pancreatic, and lung cancers) and infectious diseases (including SARS-CoV-2 and HIV). Anktiva™, ImmunityBio’s lead cytokine infusion protein, is a novel interleukin-15 (IL-15) superagonist complex and has received Breakthrough Therapy and Fast Track Designations from the
The company has established GMP manufacturing capacity at scale with cutting-edge cell manufacturing expertise and ready-to-scale facilities, as well as extensive and seasoned R&D, clinical trial, and regulatory operations, and development teams. For more information, please visit: www.immunitybio.com
- https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00147-9/fulltext
- https://www.sciencedirect.com/science/article/abs/pii/S1078143912001512
- https://ascopubs.org/doi/10.1200/JCO.2015.64.4070
- https://www.sciencedirect.com/science/article/abs/pii/S0302283808008397
- Global cancer statistics: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries: https://gco.iarc.fr/
- https://www.cancer.org/cancer/bladder-cancer/about/key-statistics.html
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3263923/
- https://doi.org/10.1016/j.eururo.2018.09.028
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1945091/
- https://www.nature.com/articles/s41585-020-0346-4
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https://onlinelibrary.wiley.com/doi/full/10.1002/1097
-0215% 2820010601% 2992% 3A5%3C697%3A%3AAID-IJC1245%3E3.0.CO%3B2-Z - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418256/
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https://ashpublications.org/blood/article/131/23/2515/36958/First-in-human-phase-1-clinical-study-of-the-IL-15
Forward Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, such as statements regarding the development of therapeutics for cancer and infectious diseases, the advancement of our Phase II and III trials, the efficacy of ImmunityBio’s product candidates as compared to existing treatment options, and regulatory approval, commercialization and commercial success of ImmunityBio’s product candidates and related matters. Statements in this press release that are not statements of historical fact are considered forward-looking statements, which are usually identified by the use of words such as “anticipates,” “believes,” “continues,” “could,” “estimates,” “expects,” “intends,” “may,” “plans,” “potential,” “predicts,” “projects,” “seeks,” “should,” “will,” and variations of such words or similar expressions. Statements of past performance, efforts, or results of our clinical trials, about which inferences or assumptions may be made, can also be forward-looking statements and are not indicative of future performance or results. Forward-looking statements are neither forecasts, promises nor guarantees, and are based on the current beliefs of ImmunityBio’s management as well as assumptions made by and information currently available to
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