Bladder Cancer

BCG Vaccine Shortage Ends in the United States

Karen McClorey Hackett — Wed, 19 Feb 2025 15:08:09 +0000

Reviewer:

Following years of inadequate supply, a recently approved recombinant Bacillus Calmette-Guérin (rBCG) is now available in the United States to treat non-muscle invasive bladder cancer (NMIBC) patients.

Access to this vaccine may end the multi-year shortage of the TICE® BCG vaccine.

ImmunityBio, Inc. announced today that the U.S. Food and Drug Administration (FDA) has authorized an expanded access program that will bring an alternative source of BCG, a standard-of-care medicine in bladder cancer, to patients in the United States.

As of February 19, 2025, ImmunityBio says shipments of the Serum Institute of India (SII) TUBERVAC-rBCG vaccine will begin immediately in the U.S.

TUBERVAC-rBCG was approved in India in 2023 as a single-dose tuberculosis (TB) prevention vaccine. In European bladder cancer phase 2 clinical trials, the rBCG vaccine has demonstrated potent immunogenicity with CD8+ and CD4+ T cell stimulation and improved safety compared to earlier BCG strains and formulations.

"With the increasing threat of supply shortages of essential medicines, the biopharmaceutical industry must innovate and secure new means of ensuring uninterrupted access to vital therapeutics," said Dr. Patrick Soon-Shiong, Founder, Executive Chairman and Global Chief Scientific and Medical Officer of ImmunityBio, in a press release.

"Our collaboration with the FDA and SII to ensure a reliable supply of this vital drug for bladder cancer patients underscores ImmunityBio's commitment to addressing critical access issues that affect so many patients."

BCG is a benign bacterium that was developed over 100 years ago as a live vaccine against TB. It has been administered to more than 4 billion individuals worldwide. In 2002, Neonatal BCG vaccination was practiced in 157 countries and territories.

SII is the world's largest manufacturer of BCG vaccines, while Merck & Co. is currently the only manufacturer of the U.S. FDA-approved TICE® BCG vaccine.

The WHO's Civil Society Taskforce on TB confirmed that 16 TB vaccines were available globally. Two gene modifications have been implemented in rBCG to improve its immunogenicity and safety compared to earlier strains and formulations of BCG.

ImmunityBio's FDA-approved ANKTIVA® is a cytokine interleukin-15 that plays a crucial role in the immune system by affecting the development, maintenance, and function of key immune cells, NK and CD8+ killer T cells, that kill cancer cells. ANKTIVA's protocol integrates rBCG vaccinations.

Sub Title:

BCG vaccine is FDA approved to bladder cancer and tuberculosis prevention

Reference:

FDA Authorizes ImmunityBio to Provide Recombinant BCG (rBCG) to Urologists to Address TICE® BCG Shortage

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Plain Language Review Explains Innovative Bladder Cancer Therapy

Donald Hackett — Thu, 18 Jul 2024 23:06:11 +0000

Reviewer:

Robert Carlson, MD

A recent Plain Language Summary of Publication stated ImmunityBio Inc.'s newly approved Anktiva® (N-803) plus Bacillus Calmette-Guérin (BCG) vaccine combination therapy produced positive results for certain bladder cancer patients.

The review of two company-sponsored clinical trials concluded that the addition of the IL-15 superagonist N-803 to BCG therapy produces a high rate of success in eliminating non-muscle invasive bladder cancer in both BCG-naive and BCG-unresponsive patients, with long-lasting effects that allow patients to avoid surgical removal of the bladder.

This clinical information is vital since bladder cancer treatment costs about $2 billion annually.

One small study was a Phase 1b study that tested increasing doses of N-803 in combination with the same dose of BCG in people with NMIBC who had never received BCG previously (BCG-naive).

The other study is a Phase 2/3 study of N-803 and BCG in people with NMIBC whose cancer wasn't eliminated by BCG alone (BCG unresponsive).

Treatments were delivered directly into the bladder once a week for six consecutive weeks.

In the Phase 1b study, the nine participants were split into three groups of 3 who received 100, 200, or 400 μg N-803 doses along with a standard 50 mg dose of BCG. In the Phase 2/3 study, one group (cohort A) of participants with carcinoma in situ disease and another group (cohort B) with papillary disease were treated with 400 μg N-803 plus 50 mg BCG. There was also a cohort C that received only 400 μg N-803.

Published by the journal Taylor and Francis Online on July 2, 2024, N-803 plus BCG eliminated NMIBC in all nine BCG-naive participants, and the effects were long-lasting, with participants remaining NMIBC-free for a range of 8.3 to 9.2 years.

In April 2024, ImmunityBio announced that the U.S. Food and Drug Administration had approved ANKTIVA plus BCG. On June 20, 2024, ImmunityBio announced the initial treatments in the U.S. had begun.

The 100-year-old BCG vaccine has been a well-established immunotherapy for NMIBC since the 1970s.

The authors of this review are affiliated with ImmunityBio, Inc., the manufacturer of N-803 and sponsor of the studies.

Sub Title:

Adding IL-15 superagonist N-803 to BCG therapy reduces non-muscle invasive bladder cancer

Reference:

A Plain Language Review

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ImmunityBio website July 2024

Bladder Cancer Immunotherapy First Commercial Doses Administered

Karen McClorey Hackett — Mon, 24 Jun 2024 19:18:58 +0000

Reviewer:

Robert Carlson, MD

Holly Lutmer PharmD

Over the past two months, people confronting a specific type of bladder cancer have received some optimistic news.

Multiple cancer patients have been treated with ANKTIVA® less than eight weeks after the U.S. FDA approved ImmunityBio Inc.’s approved immunotherapy for Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) carcinoma in situ.

On June 20, 2024, ImmunityBio confirmed the initial treatments with ANKTIVA in multiple patients in the United States. The company previously announced that ANKTIVA Drug Substance was released with two-year storage stability data sufficient for 170,000 doses.

And urologists treating eligible bladder cancer patients in the U.S. can now access the ImmunityBio CARE™ support program, which supports healthcare professionals and patients through comprehensive resources, from benefits investigation to billing assistance.

“We are pleased to see interest in our bladder cancer therapeutic among healthcare providers and are encouraged by the number of health plans covering this first-in-class therapy. These updates underscore the importance of a new treatment option for this difficult-to-treat cancer, and we’re actively working to increase access to this treatment for as many patients as we can," wrote Richard Adcock, President & CEO of ImmunityBio, in a message to Precision Vaccinations.

ImmunityBio's Cancer Moonshot program (QUILT clinical trials) launched in January 2016.

ANKTIVA's commercial launch in 2024 initiates the next era of immunotherapy beyond checkpoint inhibitors based on cytokines and natural killer (NK) cells.

The company says the drug’s novel mechanism of action activates the body’s immune system of NK and killer T cells to attack BCG-resistant tumor cells and induce memory T cells, resulting in a long duration of complete response exceeding 47 months.

ANKTIVA is a first-in-class IL-15 agonist IgG1 fusion complex consisting of an IL-15 mutant (IL-15N72D) fused with an IL-15 receptor alpha, which binds with high affinity to IL-15 receptors on NK, CD4+, and CD8+ T cells.

This fusion complex of ANKTIVA mimics the natural biological properties of the membrane-bound IL-15 receptor alpha, delivering IL-15 by dendritic cells and driving the activation and proliferation of NK cells with the generation of memory killer T cells that have retained immune memory against these tumor clones.

The proliferation of the trifecta of these immune-killing cells and the activation of trained immune memory results in immunogenic cell death, inducing a state of equilibrium with durable, complete responses. ANKTIVA has improved pharmacokinetic properties, longer persistence in lymphoid tissues, and enhanced anti-tumor activity compared to native, non-complexed IL-15 in-vivo.

In the U.S., the American Cancer Society (ACS) estimates there will be 83,190 new bladder cancer cases in 2024. The annual projected cost of treatment is over $2 billion. And the average treatment cost per patient ranges from $19,521 to $169,533 (metastatic disease).

In 2024, Anktiva is priced at $35,800 per dose, separate from the cost of Merck TICE® BCG vaccines.

Furthermore, the ACS projects over 16,000 deaths from bladder cancer this year.

More information for patients and healthcare professionals is available on Anktiva.com.

Sub Title:

ImmunityBio ANKTIVA initiates the new era of immunotherapy beyond checkpoint inhibitors

References:

ImmunityBio Announces Insurance Coverage of ANKTIVA®

ACS - Treating Bladder Cancer

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NCI - Bladder cancer 2024

100 Year Old Vaccine Protects People From Infectious Diseases

Donald Hackett — Fri, 14 Jun 2024 02:26:31 +0000

Reviewer:

Robert Carlson, MD

New research published by investigators at Massachusetts General Hospital (MGH) shows that the 100-year-old Bacillus Calmette-Guérin (BCG) vaccine, originally developed to prevent tuberculosis, protects individuals with type 1 diabetes from infectious diseases.

Two back-to-back randomized double-blinded placebo-controlled trials found that the BCG vaccine provided continuous protection for nearly the entire pandemic in the U.S., regardless of the SARS-CoV-2 variant.

The MGH Phase II and Phase III clinical trials testing BCG differed from other BCG trials in important ways.

Instead of receiving one dose of BCG, participants received five or six doses of a particularly potent strain of BCG vaccine.

“Individuals with type 1 diabetes are highly susceptible to infectious diseases and had worse outcomes when they were infected with the SARS-CoV-2 virus,” said senior author Denise Faustman, MD, PhD, director of the Immunobiology Laboratory at MGH and an Associate Professor of Medicine at Harvard Medical School, in a press release.

“....we’ve shown that BCG can protect type 1 diabetics from COVID-19 and other infectious diseases.”

The 18-month Phase III trial, published in iScience, was conducted when the highly transmissible Omicron variant was circulating.

A 15-month Phase II trial was conducted early in the pandemic; the results of that trial were published in Cell Reports Medicine.

During the COVID-19 pandemic, several international trials tested whether BCG, given as a single shot or booster to previously BCG-vaccinated adults, protected them from infection and COVID-19.

However, results from these COVID-19 booster trials were mixed in people previously vaccinated with BCG. Five randomized trials showed efficacy, and seven trials showed no benefit.

“Our study showed that the BCG vaccine neither increased the efficacy of the COVID-19 vaccine nor was it harmful to those who received the COVID-19 vaccine,” said Faustman.

The U.S. participants were followed for 36 months instead of weeks or months.

“We know that in people who are naïve to BCG vaccine, the off-target effects can take at least two years to achieve full protection,” said Faustman. “Giving multiple doses of the vaccine may speed up that process.”

The MGH trials enrolled 141 participants with type 1 diabetes; 93 people in the treatment group received five or six doses of BCG vaccine, and the 48 individuals in the placebo group received sham vaccine and were followed for 36 months to capture diverse COVID-19 genetic variants and many infectious disease exposures.

During the earlier Phase II trial (January 2020 to April 2021), when the virus was more lethal but less transmissible, the BCG vaccine’s efficacy was 92%, comparable to the efficacy of COVID-19 vaccines in healthy adults.

Over 34 months of the pandemic, the BCG vaccine had a significant efficacy of 54.3%.

The investigators also found that the BCG-treated participants had lower viral, bacterial, and fungal infection rates.

This research expanded the extensive global clinical trial database, showing that BCG administered to newborns works as a platform for all infectious diseases, maybe for decades.

In the U.S., BCG vaccinations have been an effective treatment for bladder cancer for several years.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. This research was supported by The Iacocca Foundation, Boston, MASS. No conflicts of interest were disclosed.

Sub Title:

Multi-dose BCG vaccine protects against tuberculosis, infectious diseases and bladder cancer

Reference:

BCG vaccines protect against COVID-19 and infectious diseases

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iScience May 2024

Enhanced Recombinant BCG Vaccine Awaits FDA Approval

Donald Hackett — Sat, 04 May 2024 14:57:43 +0000

Reviewer:

Robert Carlson, MD

While the standard Bacillus Calmette-Guerin (sBCG) vaccine has been in use for about 100 years and administered over 4 billion times, its clinical efficacy is debatable.

On May 2, 2024, the Serum Institute of India (SII) confirmed that it is developing a new recombinant BCG vaccine (iBCG) to enhance efficacy and address the current supply shortages.

Founded in 1966, SII, the world's largest vaccine producer, has implemented two gene modifications to improve sBCG's immunogenicity and safety, creating iBCG.

The next-generation recombinant iBCG has completed Phase1/2 human clinical studies in Europe.

According to SII's press release, iBCG has demonstrated potent immunogenicity with CD8+ and CD4+ stimulation and improved safety compared to standard BCG in European clinical trials.

Furthermore, this iBCG vaccine should provide a long-term solution for the recently approved bladder cancer vaccine.

And iBCG is intended for use with ImmunityBio's ANKTIVA® (nogapendekin alfa inbakicept-pmln) for currently approved non-muscle invasive bladder cancer (NMIBC) and potential future indications.

"The collaboration between SII and Immunity Bio will undoubtedly transform how we approach cancer treatment. It will improve global access to BCG, and at the same time, this unique therapy is the key to achieving a complete solution for bladder cancer. We are truly excited to witness the incredible impact this collaboration will have on improving patient outcomes and saving countless lives," said Mr. Adar C. Poonawalla, CEO of SII, in a press release.

Originally used as a tuberculosis vaccine, BCG administered via intravesical instillation (delivery to the bladder via a catheter) has been the standard of care for patients with NMIBCr since 1977. BCG is a benign bacterium that induces an immune response in the bladder near the cancer cells, leading to cancer clearance in many patients.

"The scale and quality of vaccines that the Serum Institute manufacturers are unparalleled, and we are honored to partner with Dr. Poonawalla and his leadership team on this important initiative," added Richard Adcock, President and CEO of ImmunityBio.

"By providing another option for BCG, we believe more NMIBC patients will benefit from this proven treatment as both a monotherapy and a combination therapy with ANTKIVA."

ImmunityBio plans to conduct clinical trials to study iBCG and sBCG manufactured by SII in combination with ANKTIVA to treat different types of bladder and other cancers.

The supply of BCG is expected to be available once the protocol for the trial has been authorized by the U.S. FDA. ImmunityBio plans to submit the protocol to the FDA and global regulatory bodies in the next 30 days.

Merck & Co. is currently the only manufacturer of the BCG TICE® vaccine approved for use in the U.S. to prevent tuberculosis and treat certain bladder cancer patients. BCG is limitedly available in the U.S.

Globally, about 16 versions of BCG are in use to prevent tuberculosis in 2024.

Sub Title:

Serum Institute of India produces recombinant BCG vaccine

References:

ImmunityBio, Serum Institute of India Agree on an Exclusive Arrangement for Global Supply of Bacillus Calmette-Guerin

Global Supply of Bacillus Calmette-Guerin (BCG) Across All Cancer Types

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US FDA Approves IL-15 Superagonist for Treating Bladder Cancer

Donald Hackett — Tue, 23 Apr 2024 16:32:53 +0000

Reviewer:

Robert Carlson, MD

Holly Lutmer PharmD

For several decades, a century-old vaccine has been used to treat a specific type of bladder cancer. In the 1970s, the Bacillus Calmette-Guérin (BCG) vaccine was approved as an immunotherapeutic treatment for bladder cancer patients.

Since then, various BCG vaccines have become the standard therapy for treating high-risk nonmuscle-invasive bladder cancer (NMIBC) patients to prevent the recurrence and progression of the disease.

Although BCG has shown moderate efficacy, researchers have sought a better therapy for bladder cancer patients.

Effective today, the U.S. Food and Drug Administration (FDA) has approved a new drug called Anktiva™ (nogapendekin alfa inbakicept-pmln) combined with Merck's TICE BCG for the treatment of adults with BCG-unresponsive NMIBC that has carcinoma in situ (CIS), with or without papillary tumors.

With the FDA's approval of Anktiva in combination with BCG, NMIBC patients who would otherwise face highly invasive surgery with life-long consequences have an important new therapeutic option with a long-term, durable, complete response, says ImmunityBio, Inc.

"The FDA's approval of Anktiva marks our launch of a next-generation immunotherapy beyond checkpoint inhibitors," said Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio, in a press release on April 22, 2024.

"Anktiva not only proliferates and activates the patient's own NK cells and CD8+ killer T cells, but also activates CD4+ T helper cells, thus enhancing the proliferation of memory killer T cells."

"This novel mechanism of action, which mimics the biology of the dendritic cell, begins the evolution of immunotherapy beyond T cells alone."

Dr. Soon-Shiong added, "We believe that by orchestrating the innate and adaptive immune system and driving long-term complete remission, ANKTIVA has the potential to play a key role as the immunotherapy beyond checkpoints in multiple tumor types in the years to come."

Bladder cancer is the 10th most commonly diagnosed cancer, and in the U.S., the American Cancer Society estimates there will be 83,190 new cases and 16,840 deaths from bladder cancer in 2024.

The annual projected total cost of bladder cancer treatment is over $2 billion.

The cost profile differs substantially among the stages of the disease. The average cost per patient varied from $19,521 (stage 0a) to $169,533 (metastatic disease).

According to the Compnay, Anktiva will be priced at $38,500 per dose.

According to the Company, Anktiva is expected to be available in the U.S. by mid-May 2024. ImmunityBio's Patient Assistance Program is expected to become operational for qualifying patients in May.

Sub Title:

ImmunityBio Anktiva N-803 Plus BCG vaccination is an FDA approved bladder cancer therapy

References:

FDA approves nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer

Bacillus Calmette-Guérin Therapy for Bladder Cancer

Economic impact of bladder cancer in the US

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Medline plus 2024

Bladder Cancer Vaccine Therapy Offers Favorable Risk-Benefit Ratio

Karen McClorey Hackett — Mon, 05 Feb 2024 18:10:00 +0000

Reviewer:

Robert Carlson, MD

Holly Lutmer PharmD

An innovative therapy that addresses the need for a safe, effective therapeutic option for bacille Calmette-Guérin (BCG) vaccine-unresponsive non-muscle invasive bladder cancer (NMIBC) patients posted additional good news today.

On February 5, 2024, ImmunityBio, Inc. announced that findings from Patient-Reported Outcomes (PROs) of participants in the phase 2/3 QUILT 3.032 study of (Anktiva™) N-803 plus BCG in bacillus Calmette-Guerin (BCG)-unresponsive NMIBC were published by the peer-reviewed journal Urology Practice.

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.

The ongoing phase 2/3 open-label multicenter registrational study QUILT 3.032 is evaluating the safety and efficacy of the investigational interleukin-15 superagonist N-803 (Anktiva and nogapendekin alfa inbakicept, NAI) in combination with a standard therapy for NMIBC, BCG, in patients who failed or in whom cancer returned after BCG monotherapy, and thus were diagnosed as BCG-unresponsive.

"The self-reported stability of health and physical function throughout 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, in a press release.

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

NMIBC represents approximately 75% of the 82,000 estimated new bladder cancer cases diagnosed in the United States in 2023. Bladder cancer is the fourth most common solid malignancy in men.

There were 16,700 estimated deaths last year, predominantly affecting males.

"Many current therapies for bladder cancer slow disease progression but can cause debilitating side effects," added Principal Investigator Karim Chamie, M.D., Associate Professor of Urology at UCLA.

"The QUILT 3.032 Quality of Life study data 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."

N-803 has received both Breakthrough Therapy and Fast Track designations by the U.S. FDA for the treatment of BCG-unresponsive NMIBC CIS, as well as Fast Track designation for BCG-unresponsive NMIBC papillary and BCG-naïve NMIBC CIS.

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

However, the FDA has set a user fee goal (Prescription Drug User Fee Act) for April 23, 2024.

The FDA has approved Merck's TICE® BCG vaccine for use in the U.S., which is used in this therapy.

Sub Title:

N-803 plus BCG bladder cancer vaccine therapy candidate has Prescription Drug User Fee Act date of April 23, 2024

References:

Unresponsive Bladder Cancer Trial Indicates Improved Physical Function in the 71% Complete Responders Suggesting a Favorable Ris

Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline: 2024 Amendment

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US CDC Bladder Cancer 2024

Non-Muscle-Invasive Bladder Cancer Vaccine Candidate Competes Resubmission to US FDA

Karen McClorey Hackett — Mon, 23 Oct 2023 16:11:30 +0000

Reviewer:

Holly Lutmer PharmD

Robert Carlson, MD

When the U.S. Food and Drug Administration (FDA) issued a complete response letter in May 2023, it indicated that the agency could not approve the biologics license application (BLA) for a Non-Muscle-Invasive Bladder Cancer (NMIBC) vaccine candidate, thousands of people impacted by this common cancer were disappointed.

However, ImmunityBio, Inc. today announced it has completed the resubmission of its BLA to the FDA for N-803 (Anktiva®), a first-in-class IL-15 superagonist, plus Bacillus Calmette-Guérin (BCG) for the treatment of BCG-unresponsive NMIBC carcinoma in situ (CIS) with or without Ta or T1 disease.

On October 23, 2023, the Company confirmed as part of this FDA resubmission, ImmunityBio provided an update on the Duration of Complete Response (CR) in BCG-unresponsive NMIBC patients with CIS ± Ta/T1 disease demonstrating a prolonged duration of remission with a median duration of CR not yet reached with a follow-up in responders exceeding 28 months.

In the responding BCG-unresponsive NMIBC patients, updated efficacy data demonstrated a probability of avoiding a cystectomy at ≥ 24 months of over 90%.

ImmunityBio also provided an update on the long-term follow-up clinical trial in BCG Naïve NMIBC patients, demonstrating a prolonged duration of complete remission in 6 out of 6 patients available for follow-up with a median survival of 8.8 years with ongoing bladder preservation to date.

These findings in both BCG-unresponsive and BCG-naïve patients demonstrate a prolonged duration of complete remission exceeding two years in the unresponsive cohort and over eight years in the BCG-naïve cohort.

This is positive news as bladder cancer is the fourth most common cancer in men, but it's less common in women, says the American Cancer Society (ACS). About 82,290 new bladder cancer cases (about 62,420 in men) are diagnosed annually.

As of October, the FDA has not approved a vaccine targeting this type of bladder cancer, and treatment options for BCG-unresponsive NMIBC patients are limited, says the ACS.

Patients with intermediate or high-risk NMIBC typically receive a treatment of transurethral resection of the bladder tumor (TURBT) followed by BCG intravesical instillation.

However, cancer will recur in 30% to 40% of patients with NMIBC despite adequate treatment with BCG.

Moreover, even among those in whom a complete response is achieved with BCG, up to 50% see their cancer return.

Recently, ImmunityBio announced that it has executed financing transactions resulting in approximately $200 million of proceeds to the Company.

As of September 11, 2023, ImmunityBio believes that it is well-positioned to fund its ongoing business operations and pre-commercialization efforts as it continues to drive toward potential regulatory approval of N-803 plus BCG for BCG-unresponsive non-muscle invasive bladder cancer.

Richard Adcock, Chief Executive Officer and President of ImmunityBio commented in a related press release, "With this additional financing, we are well positioned to execute our commercialization plans in anticipation of the approval of N-803 plus BCG in bladder cancer."

"This funding will also help support the planned expansion of our current clinical trials and the opening of new studies to explore the untapped potential of N-803 and our other platforms across multiple indications."

N-803 is a novel investigational IL-15 superagonist complex with an IL-15 mutant (IL-15N72D) bound to an IL-15 receptor α/IgG1 Fc fusion protein. The cytokine IL-15 plays a crucial role in the immune system by affecting the natural killer and T cells' development, maintenance, and function.

Merck's TICE® BCG vaccine is used in this therapy.

The N-803 vaccine candidate previously received both Breakthrough Therapy and Fast Track designations by the FDA for the treatment of BCG-unresponsive NMIBC CIS, as well as Fast Track designation for BCG-unresponsive NMIBC papillary and BCG-naïve NMIBC CIS.

Sub Title:

Anktiva N-803 is a first-in-class IL-15 superagonist plus BCG vaccine

References:

US FDA - BCG-Unresponsive Nonmuscle Invasive Bladder Cancer: Developing Drugs and Biologics for Treatment Guidance for Industry

ImmunityBio Announces Biological License Application Resubmission for N-803 in BCG-Unresponsive Non-Muscle-Invasive Bladder Canc

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Tuesday, October 24, 2023 - 05:30

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by Leandro Aguilar

Bladder Cancer Treatment Innovates in the Right Direction

Donald Hackett — Mon, 09 Jan 2023 17:31:29 +0000

Reviewer:

Robert Carlson, MD

After 40 years, the Bacillus Calmette–Guérin (BCG) vaccine has remained the most effective treatment for non–muscle-invasive bladder cancer (NMIBC), wrote researchers with Memorial Sloan Kettering Cancer Center.

However, tumor recurrence and progression are common, especially for those patients with carcinoma in situ (CIS), commented Eugene J. Pietzak, M.D. and Harry W. Herr, M.D., in an Editorial published by the NEJM Evidence on December 27, 2022.

Furthermore, therapeutic options are limited when BCG treatment fails.

Pembrolizumab was approved by the U.S. Food and Drug Administration (FDA) for this indication in 2020.

Knowing innovation was needed, BCG-unresponsive NMIBC criteria were developed in 2015 to facilitate clinical trials of novel therapies.

Since then, world-class researchers have been very productive.

For example, the NEJM Evidence published results from a clinical trial studying the novel N-803 plus BCG in adults with NMIBC CIS with or without Ta/T1 papillary disease.

The ImmunityBio's QUILT 3.032 study's primary endpoint was met in the high-risk CIS cohort with a 71% complete response rate (CR) with a median duration of response of 26.6 months.

And a 53% CR rate at 24 months and a safety profile comparable to BCG vaccination alone.

The primary endpoint was also met in the papillary NMIBC cohort, with 55% remaining disease free at 12 months.

This IL-15 superagonist N-803, referred to as nogapendekin alfa inbakicept, acts synergistically with the TICE® BCG vaccine, with a 90% probability of avoiding cystectomy over 24 months in responders.

"The efficacy and minimal toxicity of this combination represents a major advance for the care of patients with BCG-unresponsive NMIBC."

"This promising combination offers a potential alternative to cystectomy and may allow us to move beyond single-arm studies toward randomized phase 3 trials against other novel therapies, added these researchers.

These positive data form the basis of ImmunityBio's Biologics License Application for BCG-unresponsive NMIBC CIS, which the FDA accepted for review in July 2022.

Furthermore, the FDA confirmed a Prescription Drug User Fee Act date for N-803 plus BCG's use of May 23, 2023.

"The peer review and publication of data in NEJM Evidence highlights (Nov. 2022) the significance of the positive results of the QUILT 3.032 trial in patients with BCG-unresponsive NMIBC," commented Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio, in a related press release on November 10, 2022.

"These data further our understanding of N-803's unique role in potentially boosting the proliferation of natural killer and T cells while synergistically enhancing BCG efficacy."

This is exciting news as bladder cancer is the 10th most commonly diagnosed cancer with the highest lifetime treatment costs per patient.

Moreover, N-803 has been studied in more than 700 patients in multiple phase 1 and 2 trials in liquid and solid tumors.

And it is currently being studied in trials for pancreatic cancer, non-small-cell lung cancer, non-Hodgkin's lymphoma, and HIV.

And roughly 80% of new bladder cancer diagnoses are NMIBC.

While the 100-year-old BCG vaccine continues to be used for various diseases, such as tuberculosis, 14 sub-strains have evolved and are used in BCG vaccines worldwide.

This new solution could be the right innovation for many in need today.

Disclosures: Data was published by the NEJM without any industry conflicts of interest disclosures, and this news article is not paid content. The article was updated on Jan. 12. 2023, regarding the type of BCG vaccine.

Sub Title:

N-803 Plus BCG in Patients with Bladder Cancer found effective

References:

An Interleukin-15 Superagonist with BCG

IL-15 Superagonist NAI in BCG-Unresponsive Non–Muscle-Invasive Bladder Cancer

N-803 plus BCG Vaccine Therapy

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Tuesday, January 10, 2023 - 06:30

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by Gerd Altmann

NantKwest ‘Triangle-Offense’ Induces Immunogenic Cell Death

Don Hackett — Thu, 16 Jan 2020 19:20:39 +0000

Reviewer:

Robert Carlson, MD

Danielle Reiter, RN

A California based therapeutics company announced results from their Phase 1 clinical trial investigating a novel, first-in-human immunotherapy consisting of NantKwest’s off-the-shelf, PD-L1 tumor-targeted NK cells.

The findings on the Phase 1 safety and early signals of efficacy were reported on January 14, 2020, by Patrick Soon-Shiong, M.D., Chairman and CEO of NantKwest.

“We hypothesize that a common treatment protocol that harnesses both the natural-killer cell and the T cells could be effective in treating cancer across multiple tumor types.”

“This has been supported by the early signals of safety and efficacy in Phase 1 and 2 studies of NantKwest’s natural killer cells in advanced cancers.”

“We recently reported at the 2019 Society for Immunotherapy of Cancer conference complete responses in third-line Merkel cell carcinoma and fourth-line head and neck cancers when haNK CD-16 NK cells combined with Pfizer’s PD-L1 antibody, Avelumab, and with ImmunityBio’s N-803, an IL-15 superagonist were administered,” said Dr. Soon-Shiong, in a press release.

“Most recently we reported complete responses using combination therapies which included haNK, Avelumab, and N-803 in Triple-Negative Breast Cancer.

“Durable complete responses were observed in these patients who had failed all standards of care therapy for breast cancer. The results were presented at the 2019 San Antonio Breast Cancer Symposium (SABCS) in December 2019.“

“The evolution of the next generation NK in our platform was now to enable haNK cells to target tumors by expressing PD-L1 CAR (chimeric antigen receptor) on the surface of haNK NK cells.

“These PD-L1.taNK NK cells have the properties of targeting PD-L1 on tumors, without the need of an additional PD-L1 checkpoint, Avelumab.”

The FDA authorized the first-in-human safety studies of PD-L1.t-haNK (Quilt 3.064; NCT04050709) at doses of two billion cells administered bi-weekly as outpatients. The study is now enrolling the dose cohort of four billion cells per infusion.

No dose-limiting or treatment-related events were noted in patients treated to date in this first dosing cohort.

In addition, NantKwest and ImmunityBio, Inc., reported on January 14th, a compassionate use expanded access combining the PD-L1-targeted NK cell with ImmunityBio’s IL-15 fusion protein (N-803) in a patient with metastatic pancreatic cancer.

“We are extremely pleased that the FDA granted us this expanded IND authorization to initiate this novel immunotherapy treatment enabling the cross-talk of the innate natural killer system with the adaptive T cell,” said Dr. Soon-Shiong.

“Achieving complete response in metastatic pancreatic cancer and durable, complete responses in metastatic TNBC patients that have failed all current standards of care is a promising finding which may further validate our approach to orchestrate both the innate and adaptive immune system,” continued Soon-Shiong.

“Pancreatic cancer and TNBC are highly aggressive cancers with limited treatment options.”

“These results are important, proof-of-concept supporting our hypothesis that comprehensively activating the immune responses of the NK, T, and Dendritic cells, the “triangle offense”, would induce immunogenic cell death leading to durable responses, even among this challenging patient population.”

“Based on these encouraging findings, we plan to initiate clinical trials to confirm efficacy in second-line metastatic pancreatic cancer and third-line Triple Negative Breast cancer.”

NantKwest is an innovative, clinical-stage immunotherapy company focused on harnessing the power of the innate immune system to treat cancer and virally induced infectious diseases.

Cancer Immunotherapy news published by Precision Vaccinations.

Sub Title:

NantKwest Inc. believes a common treatment protocol that harnesses both the natural-killer cell and the T cells could be effective in treating cancer across multiple tumor types

Reference:

NantKwest and ImmunityBio Announce Complete Response in Metastatic Pancreatic Cancer in the First Patient to Receive PD-L1 Tumor

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