NK Cells + N-803 for Kidney and Bladder Cancer

Recruiting at 2 trial locations

Overseen By Wenxin Xu, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Systemic corticosteroids

Disqualifiers: Autoimmune disease, Cardiovascular disease, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to treating advanced kidney and bladder cancer. It combines special immune cells called CIML NK cells (Cytokine Induced Memory-like Natural Killer Cells) with a low dose of IL-2, a protein that boosts the immune system. Researchers aim to determine if this combination is safe and effective for individuals whose cancer has progressed despite previous treatments. This trial suits those with clear cell renal cell carcinoma or urothelial carcinoma who have experienced treatment failures with prior standard therapies. As an Early Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had anti-tumor chemotherapy or investigational agents within 2 weeks prior to enrollment, or immunotherapy within 4 weeks prior. Also, you cannot be on systemic corticosteroid therapy at a dose of 10 mg or more of prednisone (or equivalent) for at least 2 weeks before enrolling.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that a new type of immune cell, called cytokine-induced memory-like (CIML) natural killer (NK) cells, is safe in early trials. These cells are designed to attack cancer cells and have been well-tolerated in initial studies, with few serious side effects reported.

Trials have demonstrated that N-803, a drug that boosts the immune system, is generally safe with mild side effects. Specifically, studies with bladder cancer patients found N-803 to have low toxicity and did not cause strong immune reactions.

Both treatments remain in the early testing stages, focusing primarily on ensuring safety for humans. While early results are promising, ongoing trials will continue to closely monitor safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Cytokine Induced Memory-like Natural Killer (CIML NK) Cells combined with N-803 for treating kidney and bladder cancer because this approach leverages the body's own immune cells to fight cancer more effectively. Unlike standard treatments like surgery, chemotherapy, or radiation, which can be broadly toxic, CIML NK cells are designed to specifically target and destroy cancer cells while minimizing harm to healthy cells. Additionally, N-803 acts as an immune booster, enhancing the effectiveness of these NK cells. This innovative combination not only aims to improve patient outcomes by precisely targeting cancer cells but also holds potential for fewer side effects compared to traditional therapies.

What evidence suggests that this trial's treatments could be effective for kidney and bladder cancer?

Research has shown that a special type of immune cell, called CIML NK cells, may help treat various cancers. These cells enhance the body's ability to fight cancer. Early results from similar treatments have demonstrated promising effects against tumors, suggesting potential benefits for patients with advanced cancers. In this trial, participants will receive CIML NK cells combined with low-dose IL-2 to determine the maximum tolerated dose.

For the treatment N-803, studies have shown impressive results, particularly for bladder cancer. In one study, 71% of patients with a specific type of bladder cancer experienced a complete response, meaning their cancer was no longer detectable. This suggests that using N-803 with CIML NK cells, as studied in this trial, could be an effective option for treating kidney and bladder cancers. ^{1 3 4 6 7}

Who Is on the Research Team?

Wenxin Xu, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with advanced renal cell carcinoma or urothelial carcinoma. Participants must have measurable disease and be able to provide a sample of their tumor tissue. They should not have had any other cancer treatments like chemotherapy, radiation, or surgery within the last 4 weeks.

Inclusion Criteria

I am fully active and can carry on all my pre-disease activities without restriction.

Ability to understand and the willingness to sign a written informed consent document.

Willing to provide blood and tissue from diagnostic biopsy.

Exclusion Criteria

I have lasting side effects from previous treatments, but they are not severe.

Prior recipients of organ transplantation including allogeneic stem cell transplantation.

I have heart problems that affect my daily life.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Leukapheresis and Chemotherapy

Collection of NK cells through leukapheresis and administration of lymphodepleting chemotherapy

1 week

Multiple visits (in-person)

Treatment

Administration of CIML NK Cell Therapy and low dose IL-2

4 weeks

Daily visits for infusion and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months in-clinic, with CT, MRI, or PET scan; every 4 months follow-up in-clinic, by phone, or remotely

What Are the Treatments Tested in This Trial?

Interventions

• Cytokine Induced Memory-like Natural Killer (CIML NK) Cells
• N-803

Trial Overview

The study tests CIML NK cell therapy combined with N-803 in patients. CIML NK cells are immune cells treated to target cancer better, while N-803 boosts these cells' activity. The aim is to see if this combo is safe and how well it works against kidney and bladder cancers.

How Is the Trial Designed?

Group I: Dose Level 0: CIML NK + low dose IL-2 Experimental Treatment 2 Interventions

Participants will be enrolled in a staggered fashion into a 3+3 dose de-escalation design per protocol to establish a maximum tolerated dose (MTD) of CIML NK Cells. Dose will start at Dose Level 0. * Baseline visit. * Day -7: Apheresis for autologous NK cell collection. * Days -6 through -2: Predetermined dose of standard of care lymphodepleting chemotherapy per protocol. * Days 0: Predetermined dose of CIML NK Cell Therapy infusion 1x daily administered in-clinic or hospital. * Days 1 through 8: Low dose IL-2 every other day * Day 28 and then ever 2-3 months: CT/MRI/PET * In-clinic visit every 3 months with CT, MRI, or PET scan. * End of Treatment: in-clinic visit * Follow Up: every 4 months in-clinic, by telephone, or remotely. * If 2 or more out of 5 participants experience dose-limiting toxicities (DLTs), subsequent dose will be de-escalated to Dose Level -1.

Group II: Dose Level -1: CIML NK + low dose IL-2 Experimental Treatment 2 Interventions

Participants will complete: * Baseline visit. * Day -7: Apheresis for autologous NK cell collection. * Days -6 through -2: Predetermined dose of standard of care lymphodepleting chemotherapy per protocol. * Days 0: Predetermined dose of CIML NK Cell Therapy infusion 1x daily administered in-clinic or hospital. * Days 1 to 8: low dose IL-2 every other day * Day 28 and then ever 2-3 months: CT/MRI/PET * In-clinic visit every 3 months with CT, MRI, or PET scan. * End of Treatment: in-clinic visit * Follow Up: every 4 months in-clinic, by phone, or remotely. * If 1 or less DLTs are observed, this will be the maximum tolerated dose. If 2 or more DLTs are observed, accrual will stop.

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Kidney Cancer Association

Collaborator

Trials

1

Recruited

5+

ImmunityBio, Inc.

Industry Sponsor

Trials

75

Recruited

5,000+

Richard Adcock

ImmunityBio, Inc.

Chief Executive Officer since 2024

Information not available

Dr. Patrick Soon-Shiong

ImmunityBio, Inc.

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

Natural killer (NK) cells can develop a memory-like response after being activated by specific cytokines (IL-12, IL-15, and IL-18), allowing them to respond more effectively to future infections or tumors, which is a promising area of research for immunotherapy.

Cytokine-induced memory-like (CIML) NK cells maintain enhanced effector functions for weeks after initial activation, suggesting their potential use in treating hematologic malignancies through adoptive immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Cytokine-Induced Memory-Like Natural Killer Cells. Berrien-Elliott, MM., Wagner, JA., Fehniger, TA.[2020]

Cytokine-Induced Killer (CIK) cells are a promising option for cancer therapy due to their ability to be easily expanded and activated without needing specific antigens, allowing them to target tumor cells effectively in an HLA-independent manner.

CIK cells show reduced alloreactivity compared to traditional T cells, making them safer for use in patients, with only mild graft-versus-host disease (GVHD) reported in a few cases, and their effectiveness can be enhanced using techniques like chimeric antigen receptors and immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokines for the induction of antitumor effectors: The paradigm of Cytokine-Induced Killer (CIK) cells. Cappuzzello, E., Sommaggio, R., Zanovello, P., et al.[2022]

Autologous cytokine-induced killer (CIK) cell immunotherapy significantly improved the immune response in colorectal cancer patients, with notable increases in key immune cell subsets after 14 days of treatment.

Patients receiving CIK cell therapy showed longer progression-free survival (25.8 months) and overall survival (41.3 months) compared to the control group, indicating that this therapy can effectively enhance survival outcomes when combined with chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of cytokine-induced killer cell treatment in colorectal cancer patients: a retrospective study. Zhang, J., Zhu, L., Zhang, Q., et al.[2020]

Cytokine-induced memory-like (CIML) NK cells, stimulated with IL-12/15/18, showed significantly enhanced characteristics such as increased expression of activating receptors and granzyme B, indicating their potential for improved immune responses against tumors and viral infections.

CIML NK cells demonstrated greater degranulation capacity and higher production of IFN-γ compared to control NK cells, suggesting they could be more effective in immunotherapy applications, with specific biomarkers identified for clinical relevance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced expression of natural cytotoxicity receptors on cytokine-induced memory-like natural killer cells correlates with effector function. Carreira-Santos, S., López-Sejas, N., González-Sánchez, M., et al.[2023]

Cytokine-induced killer (CIK) cell therapy was administered to 16 patients with metastatic renal cell carcinoma (mRCC), showing minimal toxicity and no immediate adverse reactions, indicating a safe treatment option.

The therapy resulted in significant immunological responses, with 3 patients achieving complete response and 1 patient achieving partial response, suggesting that CIK cell immunotherapy is effective in enhancing the immune function against mRCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy with cytokine-induced killer cells in metastatic renal cell carcinoma. Su, X., Zhang, L., Jin, L., et al.[2010]

Circulating NK cells from bladder cancer patients showed significantly reduced cytotoxicity compared to healthy individuals, largely due to an overrepresentation of Tim-3+ NK cells, which are associated with immune exhaustion.

While proinflammatory cytokines like IL-2, IL-15, and IL-21 could moderately enhance NK cell activity, their effectiveness was limited by increased Tim-3 expression, suggesting that blocking Tim-3 could improve NK cell function in bladder cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The functional potency of natural killer cells in response to IL-2/IL-15/IL-21 stimulation is limited by a concurrent upregulation of Tim-3 in bladder cancer. Zhang, W., Feng, H., Chen, Q., et al.[2019]

Cytokine-induced memory-like (CIML) NK cells, generated by incubating NK cells with IL-12, IL-15, and IL-18, showed enhanced function and proliferation against ovarian cancer, demonstrating their potential for improved immunotherapy.

In both in vitro and in vivo models, CIML NK cells exhibited significant antitumor effects and maintained functionality even in the challenging immunosuppressive environment of ovarian cancer, suggesting a promising strategy for future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine-induced memory-like natural killer cells have enhanced function, proliferation, and in vivo expansion against ovarian cancer cells. Uppendahl, LD., Felices, M., Bendzick, L., et al.[2021]

Cytokine-induced killer (CIK) cells, which are modified T lymphocytes with both TCR and NK cell characteristics, show strong antitumoral activity while exhibiting minimal graft-versus-host disease (GvHD) toxicity, making them a promising option for cancer treatment.

CIK cells have demonstrated effective intratumoral targeting in various clinical trials, and their potential can be enhanced through genetic modification and combination with monoclonal antibodies, broadening their therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovative Clinical Perspectives for CIK Cells in Cancer Patients. Introna, M., Correnti, F.[2022]

Recent research shows that natural killer (NK) cells can develop memory-like features after short-term activation with specific cytokines (IL-12, IL-15, IL-18), leading to increased longevity and improved anticancer activity.

Preclinical studies and early clinical trials indicate that these cytokine-induced memory-like NK cells are safe and show promising effectiveness, making them a potential candidate for new immunotherapy treatments against cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine-induced memory-like natural killer cells for cancer immunotherapy. Tarannum, M., Romee, R.[2023]

Cytokine-induced memory-like (CIML) NK cells, which are generated through brief stimulation with IL-12, IL-15, and IL-18, show enhanced effector functions and long-term persistence, making them promising candidates for cancer immunotherapy.

Clinical trials have demonstrated that infusions of CIML NK cells are safe and have led to complete clinical remissions in patients with relapse/refractory acute myeloid leukemia (AML).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine-Induced Memory-Like NK Cells: From the Basics to Clinical Applications. Terrén, I., Orrantia, A., Astarloa-Pando, G., et al.[2022]

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