Phase 1 Trial of Umbilical Cord Blood Natural Killer Cells (CB-NK) Expressing Soluble IL-15 (sIL-15) and PD-L1 +/- Atezolizumab in Non-Small Cell Lung Cancer Patients Refractory to PD-1/PD-L1 Immune Checkpoint Inhibitors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Incidence of adverse events - ASTCT
研究概览
简要总结
This phase I trial studies the side effects and best dose of COH06 with or without atezolizumab in patients with non-small cell lung cancer previously treated with PD-1 and/or PD-L1 immune checkpoint inhibitors that has spread to other places in the body (advanced) and that has not responded to previous treatment (refractory). NK cells are infection fighting blood cells that can kill tumor cells. The NK cells given in this study, COH06, will come from umbilical cord blood and will have a new gene put in them that makes them express PD-L1, and express and secrete IL-15. NK cells that express PD-L1 may kill more tumor cells, and IL-15 may allow the NK cells to live longer. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving COH06 without or without atezolizumab may help control the disease in patients with non-small cell lung cancer.
详细描述
PRIMARY OBJECTIVES:
I. Assess the safety and determine the optimal biological dose (OBD) of COH06 as monotherapy and when given in combination with atezolizumab (Atezo).
II. Assess the cellular kinetics of COH06 through the detection and measurement of persistence in the peripheral blood.
SECONDARY OBJECTIVES:
I. Estimate overall response (complete response [CR] + partial response [PR]) and disease control (CR + PR + stable disease [SD]) rates, including duration.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented informed consent of the participant and/or legally authorized representative
- •Assent, when appropriate, will be obtained per institutional guidelines
- •Agreement to allow the use of archival tissue from diagnostic tumor biopsies
- •Age >= 18 years
- •Eastern Cooperative Oncology Group (ECOG) 0 or 1
- •Lung non-small cell carcinoma (NSCLC) patients with advanced, metastatic, or recurrent disease, previously treated with a PD-1 or PD-L1 immune checkpoint inhibitor, either as single agent or in combination with chemotherapy or other immunotherapy or experimental agents
- •Radiographically demonstrable tumor progression treatment on or after therapy with a PD-1/PD-L1 immune checkpoint inhibitor
- •Preserved organ function and recovery of prior drug related toxicities (except alopecia or grade 2 anemia) to grade 1 or better
- •No cytotoxic chemotherapy or immunotherapy over the three weeks prior to lymphodepletion
- •Histologically confirmed non-small cell lung cancer
- •Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1
- •Fully recovered from the acute toxic effects (except alopecia) to =< grade 1 to prior anti-cancer therapy
- •Absolute neutrophil count (ANC) >= 1,500/mm^3
- •Hemoglobin (Hgb) >= 8 g/dl
- •Platelets >= 100,000/mm^3
- •Total bilirubin =< 1.5 x upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) =< 1.5 x ULN
- •Alanine aminotransferase (ALT) =< 1.5 x ULN
- •Alkaline phosphatase (AP) =< 1.5 x ULN
- •Creatinine clearance of >= 60 mL/min per 24-hour urine test or the Cockcroft-Gault formula
- •If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (PT) =< 1.5 x ULN
- •If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
- •Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative)
- •If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed
- •Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- •Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 06 months after the last dose of protocol therapy
- •Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
排除标准
- •Autologous stem cell transplant within 1 year prior to day 1 of protocol therapy
- •Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21 days prior to day 1 of protocol therapy
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
- •Active diarrhea
- •Clinically significant uncontrolled illness
- •Active infection requiring antibiotics
- •Known history and/or positive serology for immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
- •Diagnosis of Gilbert's disease
- •Other active malignancy
- •Females only: Pregnant or breastfeeding
- •Severe (grade 3 or higher) immune related adverse events during prior PD-1 inhibitor treatment
- •Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
- •Concomitant use of other investigational agents
- •Patients with EGFR mutations or ALK translocations in their tumors, unless treatment with the indicated tyrosine kinase inhibitor has failed
- •Active brain metastases. Previously treated brain metastasis must demonstrate stability on subsequent magnetic resonance imaging (MRI) scans
- •Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
研究组 & 干预措施
Treatment (fludarabine, cyclophosphamide, COH06, atezolizumab)
Patients receive fludarabine IV on days -5 to -3, cyclophosphamide IV on days -5 to -3, and COH06 IV on days 0, 7, 14, and 21 in the absence of disease progression or unacceptable toxicity. Patients assigned to dose level 4 also receive atezolizumab IV over 60 minutes on days 0, 14, 28, and 42 in the absence of disease progression or unacceptable toxicity.
干预措施: Antineoplastic Immune Cell (Biological)
Treatment (fludarabine, cyclophosphamide, COH06, atezolizumab)
Patients receive fludarabine IV on days -5 to -3, cyclophosphamide IV on days -5 to -3, and COH06 IV on days 0, 7, 14, and 21 in the absence of disease progression or unacceptable toxicity. Patients assigned to dose level 4 also receive atezolizumab IV over 60 minutes on days 0, 14, 28, and 42 in the absence of disease progression or unacceptable toxicity.
干预措施: Biospecimen Collection (Procedure)
Treatment (fludarabine, cyclophosphamide, COH06, atezolizumab)
Patients receive fludarabine IV on days -5 to -3, cyclophosphamide IV on days -5 to -3, and COH06 IV on days 0, 7, 14, and 21 in the absence of disease progression or unacceptable toxicity. Patients assigned to dose level 4 also receive atezolizumab IV over 60 minutes on days 0, 14, 28, and 42 in the absence of disease progression or unacceptable toxicity.
干预措施: Atezolizumab (Biological)
Treatment (fludarabine, cyclophosphamide, COH06, atezolizumab)
Patients receive fludarabine IV on days -5 to -3, cyclophosphamide IV on days -5 to -3, and COH06 IV on days 0, 7, 14, and 21 in the absence of disease progression or unacceptable toxicity. Patients assigned to dose level 4 also receive atezolizumab IV over 60 minutes on days 0, 14, 28, and 42 in the absence of disease progression or unacceptable toxicity.
干预措施: Fludarabine (Drug)
Treatment (fludarabine, cyclophosphamide, COH06, atezolizumab)
Patients receive fludarabine IV on days -5 to -3, cyclophosphamide IV on days -5 to -3, and COH06 IV on days 0, 7, 14, and 21 in the absence of disease progression or unacceptable toxicity. Patients assigned to dose level 4 also receive atezolizumab IV over 60 minutes on days 0, 14, 28, and 42 in the absence of disease progression or unacceptable toxicity.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Incidence of adverse events - ASTCT
时间窗: Up to 2 years
Will be assessed and graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading system: The ASTCT grading for Cytokine Release Syndrome (CRS) and Neurotoxicity associated with Immune Effector Cells, using data obtained at each clinical assessment.
Dose limiting toxicities
时间窗: Within 28 days of the first COH06 infusion
Incidence of adverse events - CTCAE
时间窗: Up to 2 years
Will be assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) grading system: The National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events version 5.0, using data obtained at each clinical assessment.
次要结局
- Overall Response Rate (ORR)(Up to 2 years)
- Disease Control Rate (DCR)(Up to 2 years)
- Overall Survival (OS)(From the start of lymphodepletion to death from any cause, assessed up to 2 years)
- Progression-Free Survival (PFS)(From the start of lymphodepletion to the time of disease relapse, progression, or death from any cause, whichever comes first, assessed up to 2 years)
研究者
Miguel Angel Villalona
Professor and Chief
University of California, Irvine