A Phase 0 Pilot Study of Memory-like Natural Killer (NK) Cell Immune Therapy in Patients With Renal Cell Carcinoma or Urothelial Carcinoma
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)
• Histologically or cytologically confirmed, advanced or metastatic clear cell renal cell carcinoma, translocation renal cell carcinoma, chromophobe renal cell carcinoma, or urothelial carcinoma. The presence of rhabdoid or sarcomatoid differentiation is permitted if a clear cell or urothelial carcinoma component is also present.
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for nonnodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam. See Section 11 (Measurement of Effect) for the evaluation of measurable disease.
• Age ≥18 years. Because no dosing or adverse event data are currently available on the use of CIML NK cells in participants \<18 years of age, children are excluded from this study, but would be eligible for future pediatric trials.
• Participants with clear cell RCC or UC must have progression after prior treatment failure with at least one PD-1/PD-L1 immune checkpoint inhibitor that is FDA approved for treatment of UC or RCC as of the date of informed consent.
• Patients with renal cell carcinoma should also have prior treatment failure with at least one prior VEGFR TKI, or contraindication to VEGFR TKIs as determined by the treating clinician. Patients with urothelial carcinoma should have either prior treatment failure with ≥1 prior cytotoxic chemotherapy or antibody-drug conjugate. There is no limit on the number of prior lines of therapy received.
• ECOG performance status ≤1 (Karnofsky ≥80%, see Appendix A).
• Participants must meet the following organ and marrow function as defined below:
‣ absolute neutrophil count ≥1,000/mcL
⁃ hemoglobin ≥8g/dL (prior transfusion permitted)
⁃ platelets ≥75,000/mcL
⁃ total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) except if secondary to Gilbert's, then \< 3 x ULN
⁃ AST(SGOT)/ALT(SGPT) ≤3.0 × institutional ULN
⁃ creatinine ≤ 2.0 OR
⁃ glomerular filtration rate (GFR) ≥40 mL/min/1.73 m2 for participants with creatinine levels above institutional ULN.
⁃ oxygen saturation ≥ 90% on room air
⁃ left ventricular ejection fraction \> 40%
⁃ No laboratory evidence of ongoing hemolysis in opinion of investigator
• Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
• Willing to provide blood and tissue from diagnostic biopsy
• Negative serum or urine pregnancy test at screening for women of childbearing potential. Highly effective contraception for female subjects of childbearing potential throughout the study if the risk of conception exists.
• Ability to understand and the willingness to sign a written informed consent document.
• Recipients of prior allogeneic stem cell transplantation are eligible if there is no evidence of ongoing acute or chronic graft versus host disease.