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

Trial Summary

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.

What data supports the effectiveness of the treatment NK Cells + N-803 for Kidney and Bladder Cancer?

Research shows that cytokine-induced memory-like natural killer (CIML NK) cells, which are part of this treatment, have demonstrated enhanced anticancer functionality and promising clinical activity in early trials. Additionally, similar treatments using cytokine-induced killer (CIK) cells have shown effectiveness in treating renal cell carcinoma, with some patients experiencing complete or partial responses. ^{1 2 3 4 5}

Is the NK Cells + N-803 treatment safe for humans?

Early clinical trials and preclinical studies suggest that cytokine-induced memory-like (CIML) NK cells, which are part of the NK Cells + N-803 treatment, are generally safe for humans, with promising results in treating certain cancers like acute myeloid leukemia. ^{4 5 6 7 8}

What makes the NK Cells + N-803 treatment unique for kidney and bladder cancer?

This treatment is unique because it uses cytokine-induced memory-like (CIML) natural killer (NK) cells, which are enhanced by a combination of cytokines (IL-12, IL-15, and IL-18) to improve their longevity and anticancer functionality. This approach aims to overcome the limitations of traditional NK cell therapies by boosting their ability to remember and respond more effectively to cancer cells. ^{3 4 5 9 10}

What is the purpose of this trial?

The goal of this research study is to establish the safety and then to explore the effectiveness of infusing the combination of cytokine-induced memory-like (CIML) natural killer (NK) cells, a type of immune cell in the blood that is collected and bathed in special proteins to help identify and treat curtained advanced cancers, combined with low dose IL-2, which is a cytokine that activates immune cells, in advanced clear cell renal cell carcinoma and urothelial carcinoma. Names of the study therapies involved in this study are/is: * CIML NK cell therapy (a NK cell therapy) * IL-2 (a type of cytokine)

Research Team

Wenxin Xu, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

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 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) 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Cytokines for the induction of antitumor effectors: The paradigm of Cytokine-Induced Killer (CIK) cells. [2022]

2. France pubmed.ncbi.nlm.nih.gov

Effects of cytokine-induced killer cell treatment in colorectal cancer patients: a retrospective study. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Immunotherapy with cytokine-induced killer cells in metastatic renal cell carcinoma. [2010]

4. England pubmed.ncbi.nlm.nih.gov

Cytokine-induced memory-like natural killer cells for cancer immunotherapy. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Human Cytokine-Induced Memory-Like Natural Killer Cells. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Enhanced expression of natural cytotoxicity receptors on cytokine-induced memory-like natural killer cells correlates with effector function. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Innovative Clinical Perspectives for CIK Cells in Cancer Patients. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Cytokine-Induced Memory-Like NK Cells: From the Basics to Clinical Applications. [2022]

9. United States 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. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Cytokine-induced memory-like natural killer cells have enhanced function, proliferation, and in vivo expansion against ovarian cancer cells. [2021]