Study of Allogeneic Blood-derived Natural Killer Cells to Evaluate Safety and Tolerability in Cancer Refractory to Conventional Therapy

Inclusion criteria

• Pathologically confirmed diagnosis of refractory cancer that has failed at least prior line of conventional standard of care therapy.
• Diagnosed with any histologically confirmed malignancy whose disease is confirmed to be metastatic and/or unresectable for which standard curative or beneficial treatments are no longer effective.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• ≥ 4 weeks since any prior systemic therapy (excluding corticosteroid therapy) to treat the underlying malignancy (standard or investigational).
• ≥ 2 weeks since prior palliative radiotherapy.
• Complete recovery to baseline or Grade 1 NCI CTCAE v5.0 from AE of prior surgery, radiotherapy, endocrine therapy, and other therapy as applicable, with exception of grade 2 alopecia from prior chemotherapy.
• Adequate bone marrow function:

• Neutrophils: ≥ 1.5 K/µL without colony-stimulating factor support
• Platelet Count: ≥ 100 K/µL
• Hemoglobin: ≥ 9.0 g/dL without need for hematopoietic growth factor or transfusion support
• No ongoing transfusion requirements
• Adequate hepatic function:

• Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN), does not apply to patients with Gilbert's syndrome
• Serum albumin ≥ 3.0 g/dL
• ALT and AST ≤ 2.5 × ULN, unless hepatic metastases are present then < 5 x ULN
• Adequate renal function with creatinine ≤ 2.0 mg/dL.
• Coagulation: INR or aPTT ≤1.5 X ULN unless the subject is receiving anticoagulant therapy.
• Adequate pulmonary function as assessed by pulse oximetry (>92% oxygen saturation on room air).
• Negative pregnancy test for women of childbearing potential (i.e., all women except those who are post menopause for ≥ 1 year or who have a history of hysterectomy or surgical sterilization) and agree to use of effective contraception (hormonal or barrier method of birth control) during study.
• Male participants and female participants of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception

Exclusion criteria

• Pregnant and/or lactating females.
• Life expectancy of less than three months.
• Currently being treated by "biological therapy" as defined by the National Cancer Institute (https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/bio-therapies-fact-sheet) Examples include checkpoint inhibitors, adoptive cell transfer, monoclonal antibodies, treatment vaccines, cytokines, CAR-T therapy, and natural killer (NK) cell therapy.
• Participants that are actively positive for COVID.
• Autoimmune disease requiring therapy; immunodeficiency, or any disease process requiring immunosuppressive therapy, with exception to the following:

• intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);
• Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent;
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• Prior clinical trial requiring participant to receive an investigational drug within four weeks of enrollment.
• Live vaccine within 30 days prior to enrollment.
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
• Mental or psychological illness preventing cooperation with treatment, efficacy evaluations.
• Participants who have undergone prior organ transplantation, including allogeneic stem-cell transplantation.