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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- To assess the safety profile
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 <
- •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.
排除标准
- •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.
研究组 & 干预措施
Cohort 1 - Low dose SNK01
SNK01 (low dose) administered once a week for five weeks.
干预措施: SNK01 (Biological)
Cohort 2 - Medium dose SNK01
SNK01 (medium dose) administered once a week for five weeks.
干预措施: SNK01 (Biological)
Cohort 3 - High dose SNK01
SNK01 (high dose) administered once a week for five weeks.
干预措施: SNK01 (Biological)
Cohort 4 - SNK01 with avelumab
SNK01 (high dose) administered in combination with avelumab once every two weeks (14-day cycle) for five cycles.
干预措施: SNK01 (Biological)
Cohort 4 - SNK01 with avelumab
SNK01 (high dose) administered in combination with avelumab once every two weeks (14-day cycle) for five cycles.
干预措施: Avelumab (Drug)
Cohort 4 - SNK01 with pembrolizumab
SNK01 (high dose) administered in combination with pembrolizumab once every three weeks (21-day cycle) for five cycles.
干预措施: SNK01 (Biological)
Cohort 4 - SNK01 with pembrolizumab
SNK01 (high dose) administered in combination with pembrolizumab once every three weeks (21-day cycle) for five cycles.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
To assess the safety profile
时间窗: 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.
次要结局
- To assess clinical objective response rate (ORR) of SNK01 in patients with refractory cancer(Up to 12 months)
- To assess clinical objective response rate (ORR) of SNK01 in combination with avelumab in patients with refractory cancer(Up to 12 months)
- To assess clinical objective response rate (ORR) of SNK01 in combination with pembrolizumab in patients with refractory cancer(Up to 12 months)