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

NCT ID: NCT03941262

Last Updated: 2023-11-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-15
• Study Completion Date: 2023-02-17

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1 - Low dose SNK01

SNK01 (low dose) administered once a week for five weeks.

Group Type: EXPERIMENTAL

SNK01

Intervention Type: BIOLOGICAL

Patient-specific ex vivo expanded autologous natural killer cells

Cohort 2 - Medium dose SNK01

SNK01 (medium dose) administered once a week for five weeks.

Group Type: EXPERIMENTAL

SNK01

Intervention Type: BIOLOGICAL

Patient-specific ex vivo expanded autologous natural killer cells

Cohort 3 - High dose SNK01

SNK01 (high dose) administered once a week for five weeks.

Group Type: EXPERIMENTAL

SNK01

Intervention Type: BIOLOGICAL

Patient-specific ex vivo expanded autologous natural killer cells

Cohort 4 - SNK01 with avelumab

SNK01 (high dose) administered in combination with avelumab once every two weeks (14-day cycle) for five cycles.

Group Type: EXPERIMENTAL

SNK01

Intervention Type: BIOLOGICAL

Patient-specific ex vivo expanded autologous natural killer cells

Avelumab

Intervention Type: DRUG

Avelumab is a humanized monoclonal antibody immune checkpoint blockade immunotherapy that targets the programmed cell death-ligand 1 (PD-L1).

Cohort 4 - SNK01 with pembrolizumab

SNK01 (high dose) administered in combination with pembrolizumab once every three weeks (21-day cycle) for five cycles.

Group Type: EXPERIMENTAL

SNK01

Intervention Type: BIOLOGICAL

Patient-specific ex vivo expanded autologous natural killer cells

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab is a humanized monoclonal antibody immune checkpoint blockade immunotherapy that targets the programmed cell death receptor-1 (PD-1).

Interventions

SNK01

Patient-specific ex vivo expanded autologous natural killer cells

Intervention Type: BIOLOGICAL

Avelumab

Avelumab is a humanized monoclonal antibody immune checkpoint blockade immunotherapy that targets the programmed cell death-ligand 1 (PD-L1).

Intervention Type: DRUG

Pembrolizumab

Pembrolizumab is a humanized monoclonal antibody immune checkpoint blockade immunotherapy that targets the programmed cell death receptor-1 (PD-1).

Intervention Type: DRUG

Other Intervention Names

Bavencio; Keytruda

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NKGen Biotech, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul Chang, MPH

Role: STUDY_DIRECTOR

NKGen Biotech, Inc.

Locations

Sarcoma Oncology Research Center

Santa Monica, California, United States

Countries

United States

Other Identifiers

SNK01-US01

Identifier Type: -

Identifier Source: org_study_id