On February 16, 2021 ImmunityBio, Inc., a privately-held immunotherapy company, reported the oral presentation of "Phase II/III 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)" during a session at the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (Press release, NantKwest, FEB 16, 2021, https://nantkwest.com/immunitybio-announces-asco-genitourinary-cancer-symposium-presentation-of-phase-2-3-trial-for-bcg-unresponsive-non-muscle-invasive-bladder-cancer-cis-with-71-complete-response-rate/ [SID1234575104]).
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The data showed 51 out of 72 evaluable patients (71%), with 10.7 months median follow-up, had a complete response at any time to intravesical BCG plus N-803, also called AnktivaÔ (95% confidence interval), meeting the primary endpoint of the study. In addition, the study showed 59% probability of these patients maintaining a complete response for at least 12 months, with an estimated median duration of complete response of 19.2 months to date using Kaplan-Meier methods.
"The high rates of complete response without serious adverse events indicates that the combination of BCG plus N-803 is a promising alternative to existing therapies and compares favorably to the other approved options valrubicin and pembrolizumab," said presenting author Karim Chamie, M.D., Associate Professor of Urology, David Geffen School of Medicine at UCLA.
No immune-related adverse events were seen in any patients, and only 1% of patients reported treatment emergent serious adverse events, but none of which were treatment-related. Additionally, 24% of patients received additional chemotherapy and other therapies (excluding BCG) between last dose of BCG and study entry, and 100% of patients received prior BCG, thus the data support the potential for Anktiva plus BCG as a novel option for BCG unresponsive CIS, a therapeutically challenging disease. Patients with BCG unresponsive CIS disease face surgical removal of the bladder, a procedure fraught with high mobidity and mortality.
Bladder cancer has a high incidence worldwide; it caused 212,536 deaths and an estimated 73,278 new cases were diagnosed in 20201. In the United States, bladder cancer is the fourth most commonly diagnosed solid malignancy in men and the twelfth for women; The American Cancer Society estimates 80,470 new cases and 17,670 deaths in 20192. Approximately 75-85% of all newly diagnosed cases of bladder cancer are non-muscle invasive bladder cancer (NMIBC)3.
The 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) 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 December 2019, the FDA granted ImmunityBio Breakthrough Therapy Designation based on interim Phase 2 data indicating the primary endpoint of the trial was already met.
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. 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.
The Urgent, Unmet Need to Treat NMIBC and Avoid Cystectomy
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 for these patients 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 30% will progress and succumb to their disease over a 15-year period, and another 50% will undergo radical cystectomy of the bladder in an attempt to control their disease4.
For high-risk NMIBC patients who are BCG-unresponsive with persistent or recurrent disease, treatment guidelines recommend a surgical procedure called radical cystectomy, a surgery to remove the entire bladder that may require removal of other surrounding organs. In men, removal of the prostate may be necessary, and in women, surgeons may also remove the uterus, fallopian tubes, ovaries and cervix, and occasionally a portion of the vagina. Despite the advent of minimally invasive procedures and robotic techniques, the 90-day mortality and morbidity rates in patients who undergo cystectomy remain unacceptably high at 5.1-8.1% and 28-64%, respectively5. Based on this urgent need, FDA published guidance in February 2018 to address BCG unresponsive non-muscle invasive bladder cancer (NMIBC), stating that the goal of therapy in patients with BCG-unresponsive NMIBC is to avoid cystectomy.
NantKwest Transaction
ImmunityBio separately announced today that it has entered into an agreement to combine in a stock-for-stock transaction with NantKwest, Inc. (NASDAQ: NK). The combination will create a leading immunotherapy and cell therapy companies focused on oncology and infectious disease.