• Safety Measure: Adverse Events [ Time Frame: From enrollment to end of treatment at nine weeks] ]
  Frequency and type of adverse events, assessed using NCI-CTCAE v 5.0, )
• Safety Measure: Cytokine Release Syndrome (CRS) [ Time Frame: From enrollment to end of treatment at nine weeks ]
  CRS revised grading system (Lee et al., Blood 2014 July 10; 124(2) 188-95

• To assess clinical objective response rate (ORR) of SNK01 in patients with refractory cancer [ Time Frame: Up to 12 months ]
  Objective response rate (ORR) is defined by the percentage of subjects who achieve a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1.
• To assess clinical objective response rate (ORR) of SNK01 in combination with avelumab in patients with refractory cancer [ Time Frame: Up to 12 months ]
  Objective response rate (ORR) is defined by the percentage of subjects who achieve a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1.
• To assess clinical objective response rate (ORR) of SNK01 in combination with pembrolizumab in patients with refractory cancer [ Time Frame: Up to 12 months ]
  Objective response rate (ORR) is defined by the percentage of subjects who achieve a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1.

• Refractory Cancer
• Metastatic Cancer
• Recurrent Cancer
• Unresectable Carcinoma
• Solid Tumor, Adult
• Advanced Cancer
• Advanced Solid Tumor

• Biological: SNK01
  Patient-specific ex vivo expanded autologous natural killer cells
• Drug: Avelumab
  Avelumab is a humanized monoclonal antibody immune checkpoint blockade immunotherapy that targets the programmed cell death-ligand 1 (PD-L1).
  Other Name: Bavencio
• Drug: Pembrolizumab
  Pembrolizumab is a humanized monoclonal antibody immune checkpoint blockade immunotherapy that targets the programmed cell death receptor-1 (PD-1).
  Other Name: Keytruda

• Experimental: Cohort 1 - Low dose SNK01
  SNK01 (low dose) administered once a week for five weeks.
  Intervention: Biological: SNK01
• Experimental: Cohort 2 - Medium dose SNK01
  SNK01 (medium dose) administered once a week for five weeks.
  Intervention: Biological: SNK01
• Experimental: Cohort 3 - High dose SNK01
  SNK01 (high dose) administered once a week for five weeks.
  Intervention: Biological: SNK01
• Experimental: Cohort 4 - SNK01 with avelumab
  SNK01 (high dose) administered in combination with avelumab once every two weeks (14-day cycle) for five cycles.
  Interventions:

  • Biological: SNK01
  • Drug: Avelumab
• Experimental: Cohort 4 - SNK01 with pembrolizumab
  SNK01 (high dose) administered in combination with pembrolizumab once every three weeks (21-day cycle) for five cycles.
  Interventions:

  • Biological: SNK01
  • Drug: Pembrolizumab

Inclusion Criteria:

• Voluntary written informed consent signed by patient, obtained prior to study enrollment.
• Males and females ages 18 to 75 years, inclusive.
• Pathologically confirmed diagnosis of refractory cancer that has failed three or more prior lines 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 <2.
• At least 4 weeks since any prior systemic therapy (excluding corticosteroid therapy) to treat the underlying malignancy (standard or investigational).
• At least 2 weeks since prior palliative radiotherapy.

• Adequate bone marrow function:

  • Neutrophils: 2.0-8.0 K/uL
  • Platelet Count: 140-440 K/uL
  • Hemoglobin: 10.0-18.0 g/dL
  • No ongoing transfusion requirements

• Adequate hepatic function:

  • Serum total bilirubin < 1.5 x upper limit of normal (ULN)
  • Serum albumin ≥ 3.0 g/dL
  • Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5 x ULN
  • International normalized ratio (INR) ≤ 1.5 x ULN
• Adequate renal function with creatinine ≤ 2.0 mg/dL.
• Negative pregnancy test for women of childbearing potential and use of effective contraception (hormonal or barrier method of birth control) during study.

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 (example: checkpoint inhibitors, adoptive cell transfer, monoclonal antibodies, treatment vaccines, cytokines, Bacillus Calmette-Guerin (BCG), chimeric antigen receptor T cell therapy (CAR-T), and natural killer cell therapy).
• Patients tested positive for hepatitis B and/or C surface antigen.
• High fever or any active or unresolved infection, including human immunodeficiency virus (HIV) positive.
• Autoimmune disease requiring therapy; immunodeficiency, or any disease process requiring immunosuppressive therapy.
• Prior clinical trial requiring patient to receive an investigational drug within two weeks of enrollment.
• Congestive heart failure, unstable angina or other underlying cardiac disease; history of thrombosis currently requiring anticoagulation.
• Mental or psychological illness preventing cooperation with treatment, efficacy evaluations, or unable to understand the informed consent process.
• Subjects who have undergone prior organ transplantation, including allogeneic stem-cell transplantation.
• Adult subjects who lack capacity to consent for themselves and for whom consent must be provided by a legally authorized representative.
• For SNK01+avelumab arm only: Subjects with prior hypersensitivity to avelumab or its excipients, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3).
• For SNK01+avelumab arm only: Subjects with a significant immune-mediated adverse event due to a prior checkpoint inhibitor immunotherapy that led to permanent discontinuation of the therapy.