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

NKGen Biotech

Status and phase: Completed; Phase 1

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

Treatments: Biological: SNK01; Drug: Avelumab; Drug: Pembrolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03941262

SNK01-US01

Details and patient eligibility

About

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.

Enrollment: 27 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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27 participants in 5 patient groups

Cohort 1 - Low dose SNK01

Experimental group

Description:

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

Treatment:

Biological: SNK01

Cohort 2 - Medium dose SNK01

Experimental group

Description:

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

Treatment:

Biological: SNK01

Cohort 3 - High dose SNK01

Experimental group

Description:

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

Treatment:

Biological: SNK01

Cohort 4 - SNK01 with avelumab

Experimental group

Description:

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

Treatment:

Biological: SNK01

Drug: Avelumab

Cohort 4 - SNK01 with pembrolizumab

Experimental group

Description:

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

Treatment:

Biological: SNK01

Drug: Pembrolizumab