Safety of SNK01 in Subjects With Pathologically Confirmed Metastatic and/or Unresectable Cancer Refractory to Conventional Therapy

• ClinicalTrials.gov Identifier: NCT03941262
• Recruitment Status: Active, not recruiting
• First Posted: May 7, 2019
• Last Update Posted: March 15, 2023
• Sponsor: NKGen Biotech, Inc.
• Information provided by (Responsible Party): NKGen Biotech, Inc.

Tracking Information

• First Submitted Date: May 3, 2019
• First Posted Date: May 7, 2019
• Last Update Posted Date: March 15, 2023
• Actual Study Start Date: July 15, 2019
• Actual Primary Completion Date: February 17, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 18, 2020)

To assess the safety profile [ Time Frame: Up to 6 months ]

Assessed by the incidence and severity of dose limiting toxicity (DLT) and other adverse events graded according to the National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 5.0, or the cytokine release syndrome revised grading system.

Original Primary Outcome Measures (submitted: May 6, 2019)

• 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

Current Secondary Outcome Measures (submitted: July 18, 2020)

• 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.

Original Secondary Outcome Measures (submitted: May 6, 2019)

Preliminary Efficacy Measure: Objective Response [ Time Frame: From enrollment to end of treatment at nine weeks ]

Percentage of participants with objective response, either complete response or partial response, assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and iRECIST

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety of SNK01 in Subjects With Pathologically Confirmed Metastatic and/or Unresectable Cancer Refractory to Conventional Therapy
• Official Title: Phase 1, Open-Label, Safety Study of Escalating Doses of Ex Vivo Expanded, Autologous Natural Killer Cells in Patients With Pathologically Confirmed Cancer Refractory to Conventional Therapy
• Brief Summary: The purpose of the study is to evaluate the safety and preliminary efficacy of SNK01 (autologous natural killer cell), as a single agent and in combination with avelumab or pembrolizumab, for the treatment of subjects with advanced and/or metastatic refractory cancer that has failed three or more prior lines of conventional standard of care therapy.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

• 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

Study Arms

• 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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: July 18, 2020): 27
• Original Estimated Enrollment (submitted: May 6, 2019): 9
• Estimated Study Completion Date: May 2023
• Actual Primary Completion Date: February 17, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03941262
• Other Study ID Numbers: SNK01-US01
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: NKGen Biotech, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: NKGen Biotech, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Paul Chang, MPH; NKGen Biotech, Inc.

• PRS Account: NKGen Biotech, Inc.
• Verification Date: March 2023