- 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% and 18%, respectively1 & 2
- In addition, for patients with papillary disease, a disease-free survival rate at 18 months of 53%, which more than doubles the 25% rate published by the International Bladder Cancer Group as clinically meaningful
- A cystectomy avoidance rate of over 90% (91% of CIS patients and 95% 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 Sam Chang, M.D., Urologic Surgery Chief Surgical Officer, Vanderbilt Ingram Cancer Center and trial investigator. “This study suggests that BCG induces trained immunity as the prime, while N-803 serves as a vital boost for innate immune memory. These results of high efficacy activity and excellent safety profile set a new bar for NMIBC treatment, and together with the familiar and favorable mode of administration, will advance our current standards of care for patients with bladder cancer.”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 30% durable response at 18 to 24 months for a clinically meaningful therapy “is likely too high and may not be realistically achievable,”3 according to recommendations published in the Journal of Clinical Oncology. This “realistically unachievable” endpoint of 30% durable response at 18 months has in fact now been achieved and exceeded with the combination of Anktiva and BCG in this trial reported today. Taken together, the high rates of complete response, cystectomy avoidance, avoidance of progression to muscle invasive disease in the patients that responded, and the prolonged duration of complete response, as well as the favorable safety profile, places this novel immunotherapy combination at the forefront of both existing approved and potential treatments for bladder cancer patients
“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 Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer of ImmunityBio. “N-803, our IL-15 superagonist which proliferates NK and T cells, 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.”
“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
- 1 Month 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 Friday, February 18 during an oral presentation at the 2022 ASCO Genitourinary Cancers Symposium titled "Phase II/III clinical results of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC)."
References:
- 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
Source: "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". 2022. Immunitybio.