Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Transitional Cell

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Transitional Cell Carcinoma

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

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, 7, 14, 35, 56, 77, and 98: Predetermined dose of N-803 1x daily.
* 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.

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, 7, 14, 35, 56, 77, and 98: Predetermined dose of N-803 1x daily.
* 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.

Autologous, cytokine induced memory-like natural killer cells, via intravenous (into the vein) infusion per protocol.

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

Recombinant Human Superagonist, 2 mL single-dose/single-use vial, via subcutaneous (under the skin) injection per protocol.

N-803

Wenxin Xu, MD

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 N-803, a medication that increases the activity of Interleukin-15, 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)
* N-803 (a type of recombinant human IL-15 superagonist)

The purpose of this research study is to obtain information on the feasibility of the combination of CIML NK cell therapy with N-803 to treat advanced clear cell renal cell carcinoma and urothelial carcinoma. This is the first time that the specific combination of CIML NK cells and NIZ803 (IL-15 superagonist) will be given to humans.

The U.S. Food and Drug Administration (FDA) has not approved CIML NK cells post Maintenance Culture as a treatment for renal cell carcinoma or urothelial carcinoma.

The FDA has not approved N-803 as a treatment for renal cell carcinoma or urothelial carcinoma.

This research study involves screening for eligibility, collection of natural killer (NK) cells in a process called leukapheresis, treatment visits, X-rays, Computerized Tomography (CT) scans, Magnetic Resonance Imaging (MRI) scans, Positron Emission Tomography (PET) scans, blood tests, urine tests, echocardiograms, electrocardiograms (ECGs), and tumor biopsies.

Participants will be in this research study for up to 5 years from the CIML NK cell infusion.

It is expected that about 5 people will take part in this research study.

This research is supported by a grant from the Kidney Cancer Association. ImmunityBio is supporting this research by providing the N-803 medication.

Memory-like Natural Killer (NK) Cell Therapy With N-803 in Patients With Renal Cell Carcinoma or Urothelial Carcinoma

A Phase 0 Pilot Study of Memory-like Natural Killer (NK) Cell Immune Therapy in Combination With N-803 in Patients With Renal Cell Carcinoma or Urothelial Carcinoma

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Feasibility is defined as the ability to collect cells, generate product, and administer CIML NK plus 6-day maintenance culture cells to participants. FFR is defined as the proportion pf participants that do not achieve the feasibility during the maintenance phase.

Kidney Cancer Association

ImmunityBio, Inc.

Dana-Farber Cancer Institute

Principal Investigator

Spots Global Cancer Trial Database for advanced clear renal cell carcinoma