Clinical trial NCT03941262: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Refractory Cancer
Metastatic Cancer
Recurrent Cancer
Unresectable Carcinoma
Solid Tumor, Adult
Advanced Cancer
Advanced Solid Tumor
Keywords: Natural killer cell
NK cell
Expanded natural killer cell
Immunotherapy
Cancer
Metastatic cancer
Advanced solid tumor
Refractory cancer
Recurrent cancer
Unresectable carcinoma
Solid tumor
Neoplasms
Lead sponsor: NKGen Biotech, Inc.
Sponsor class: INDUSTRY
First posted: 2019-05-07
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: To assess the safety profile
timeFrame: Up to 6 months
Secondary outcomes:
measure: To assess clinical objective response rate (ORR) of SNK01 in patients with refractory cancer
timeFrame: Up to 12 months
measure: To assess clinical objective response rate (ORR) of SNK01 in combination with avelumab in patients with refractory cancer
timeFrame: Up to 12 months
measure: To assess clinical objective response rate (ORR) of SNK01 in combination with pembrolizumab in patients with refractory cancer
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Sarcoma Oncology Research Center
state: California
Study officials:
affiliation: NKGen Biotech, Inc.
name: Paul Chang, MPH
role: STUDY_DIRECTOR
References: