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

July 12, 2023 updated by: NKGen Biotech, Inc.

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

27

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Santa Monica, California, United States, 90403
        • Sarcoma Oncology Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1 - Low dose SNK01
SNK01 (low dose) administered once a week for five weeks.
Biological: SNK01
Patient-specific ex vivo expanded autologous natural killer cells
Experimental: Cohort 2 - Medium dose SNK01
SNK01 (medium dose) administered once a week for five weeks.
Biological: SNK01
Patient-specific ex vivo expanded autologous natural killer cells
Experimental: Cohort 3 - High dose SNK01
SNK01 (high dose) administered once a week for five weeks.
Biological: SNK01
Patient-specific ex vivo expanded autologous natural killer cells
Experimental: Cohort 4 - SNK01 with avelumab
SNK01 (high dose) administered in combination with avelumab once every two weeks (14-day cycle) for five cycles.
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 Names:
  • Bavencio
Experimental: Cohort 4 - SNK01 with pembrolizumab
SNK01 (high dose) administered in combination with pembrolizumab once every three weeks (21-day cycle) for five cycles.
Biological: SNK01
Patient-specific ex vivo expanded autologous natural killer cells
Drug: Pembrolizumab
Pembrolizumab is a humanized monoclonal antibody immune checkpoint blockade immunotherapy that targets the programmed cell death receptor-1 (PD-1).
Other Names:
  • Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 12 months
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.
Up to 12 months
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.
Up to 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NKGen Biotech, Inc.

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 15, 2019

Primary Completion (Actual)

February 17, 2023

Study Completion (Estimated)

September 1, 2023

Study Registration Dates

First Submitted

May 3, 2019

First Submitted That Met QC Criteria

May 6, 2019

First Posted (Actual)

May 7, 2019

Study Record Updates

Last Update Posted (Actual)

July 14, 2023

Last Update Submitted That Met QC Criteria

July 12, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SNK01-US01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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