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

Study Overview
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Brief Summary
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The goal of this clinical trial is to test SNK02 in participants with pathologically confirmed cancer that is refractory to conventional therapy. The main questions it aims to answer are: Is SNK02 safety and tolerable when administered weekly as an intravenous infusion What is the maximum dose that is tolerated of SNK02 Participants will be administered SNK02 weekly for 8 weeks and undergo medical evaluation to provide initial clinical safety data for the treatment of cancer with allogeneic NK cells as a monotherapy treatment.

Official Title
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A Phase 1, Open-Label, Dose Escalation Study of Allogeneic Blood-derived Natural Killer Cells to Evaluate Safety and Tolerability in Participants With Pathologically Confirmed Cancer Refractory to Conventional Therapy

Conditions
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Pathologically Confirmed Cancer Refractory to Conventional Therapy, Refractory Cancer, Metastatic Cancer, Recurrent Cancer, Solid Tumor, Adult, Solid Tumor, Advanced Cancer, Advanced Solid Tumor

Intervention / Treatment
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* Biological: SNK02


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>SNK02 will be administered as an IV infusion weekly for 8 weeks. | Biological: SNK02<br>* SNK02 is ex vivo expanded allogeneic NK cells for IV injection, is a light-yellow cryopreserved cell suspension consisting of NK cells isolated from healthy donor's peripheral blood mononuclear cells.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with dose-limiting toxicity as assessed by labs, PE and AEs | Evaluate the safety and tolerability of SNK02 assessed by labs, PE and AEs | 4 weeks | 
| MTD and/or RP2D | Determine the maximum tolerated dose or the ready for Phase 2 dose of SNK02 | 8 weeks | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | Evaluate the safety and tolerability of SNK02 assessed by labs, PE and AEs | 12 weeks |