ImmunityBio Announces Primary Endpoint Met of Phase 2/3 Trial for BCG Unresponsive Non-Muscle Invasive Bladder Cancer CIS with 72% Complete Response Rate

December 21, 2020 |

7 min read

QUILT 3.032 study completes planned enrollment of BCG unresponsive non-muscle invasive bladder cancer CIS cohort with 59% probability of patients maintaining complete response for at least 12 months

Dec. 21, 2020 11:05 UTC

QUILT 3.032 study completes planned enrollment of BCG unresponsive non-muscle invasive bladder cancer CIS cohort with 59% probability of patients maintaining complete response for at least 12 months
Over 85% of patients in this study have avoided a cystectomy to date
Breakthrough status for ImmunityBio’s superagonist Anktiva N-803 in this indication
Biologics License Application filing anticipated in second half of 2021

CULVER CITY, Calif.--(BUSINESS WIRE)-- ImmunityBio, Inc., a privately-held immunotherapy company, today announced positive data from the first cohort of a pivotal Phase 2/3 trial (QUILT 3.032) for non-muscle invasive bladder cancer in high risk carcinoma in situ (CIS) disease. The data showed 51 out of 71 evaluable patients (72%) had a complete response (at any time) to intravesical BCG plus N-803 (Anktiva), with 59% probability of these patients maintaining a complete response for at least 12 months, with a median duration of complete response of 19.2 months to date.

With the observed efficacy and only 1% of patients reporting treatment emergent serious adverse events, but none of which were treatment-related, 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 morbidity and mortality.

Bladder cancer has a high incidence worldwide; it caused 212,536 deaths and an estimated 573,278 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.

“The high rates of progression and recurrence for NMIBC make it one of the most expensive cancers to treat. This preliminary data is heartening and provides additional evidence of the potential for ImmunityBio’s Anktiva in treating a serious and potentially fatal cancer, for which the alternative is a highly invasive radical cystectomy,” said Patrick Soon-Shiong, M.D., Chairman and CEO of ImmunityBio. “We expect to file a Biologics License Application following a meeting with the FDA in 2021.”

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.

About ImmunityBio

ImmunityBio, Inc. is a late-clinical-stage immunotherapy company developing next-generation therapies that drive immunogenic mechanisms for defeating cancers and infectious diseases. The company’s immunotherapy platform activates both the innate (natural killer cell and macrophage) and adaptive (T-cell) immune systems to create long-term “immunological memory.” This novel approach is designed to eliminate the need for high-dose chemotherapy, improve upon the outcomes of current CAR T-cell therapies, and extend beyond checkpoint inhibitors.

ImmunityBio’s platform is based on the foundation of three separate modalities: antibody cytokine fusion proteins, synthetic immunomodulators, and second-generation human adenovirus (hAd5) vaccine technologies.

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 U.S. Food and Drug Administration (FDA) for BCG-unresponsive CIS non-muscle invasive bladder cancer (NMIBC). The company is also in Phase 2 or 3 trials for indications such as first- and second-line lung cancer, triple-negative breast cancer, metastatic pancreatic cancer, recurrent glioblastoma, and soft tissue sarcoma in combination with the company’s synthetic immune modulator (Aldoxorubicin).

ImmunityBio is also developing therapies, including vaccines, for the prevention and treatment of HIV, influenza, and the coronavirus SARS-CoV-2 with its second-generation human adenovirus (hAd5) vaccine technologies.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements concerning or implying that ImmunityBio will be successful in improving the treatment of the novel coronavirus, the timing and results of the clinical development of had5-COVID -19 oral capsule vaccine, or whether ImmunityBio will be successful in gaining regulatory approval of, commercializing or distributing the vaccine. Risks and uncertainties related to these endeavors include, but are not limited to the successful completion of the currently contemplated Phase 1 trials and the currently enrolling Phase 2 trial and subsequent clinical development and FDA approval of the vaccine on the currently anticipated timeline, if at all, as well as manufacturing and distribution challenges., Risks and uncertainties related to this endeavor include, but are not limited to, the company’s beliefs regarding the success, cost, and timing of its development activities and clinical trials.

Forward-looking statements are based on management’s current expectations and are subject to various risks and uncertainties that could cause actual results to differ materially and adversely from those expressed or implied by such forward-looking statements. Accordingly, these forward-looking statements do not constitute guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements. These forward-looking statements speak only as of the date hereof, and we disclaim any obligation to update these statements except as may be required by law.