- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT05334329
Células Natural Killer (NK) geneticamente modificadas com ou sem atezolizumabe para o tratamento de câncer de pulmão de células não pequenas previamente tratado com inibidores do ponto de verificação imune PD-1 e/ou PD-L1
Ensaio de Fase 1 de Células Natural Killer do Sangue do Cordão Umbilical (CB-NK) Expressando IL-15 Solúvel (sIL-15) e PD-L1 +/- Atezolizumabe em Pacientes com Câncer de Pulmão de Células Não Pequenas Refratários a PD-1/PD-L1 Inibidores de Ponto de Verificação Imunológica
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.
Visão geral do estudo
Status
Condições
- Carcinoma metastático de pulmão de células não pequenas
- Carcinoma Pulmonar Refratário de Células Não Pequenas
- Câncer de Pulmão Estágio IVA AJCC v8
- Câncer de Pulmão Estágio IVB AJCC v8
- Câncer de Pulmão Estágio III AJCC v8
- Câncer de Pulmão Estágio IV AJCC v8
- Câncer de Pulmão Estágio IIIA AJCC v8
- Câncer de Pulmão Estágio IIIB AJCC v8
- Câncer de Pulmão Estágio IIIC AJCC v8
- Carcinoma Pulmonar de Células Não Pequenas Avançado
- Carcinoma Pulmonar de Células Não Pequenas Recorrente
Descrição detalhada
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.
II. Estimate the progression free survival (PFS) and overall survival (OS) rate, at 6-months and 1-year post (first) COH06 cell infusion.
CORRELATIVE STUDY OBJECTIVES:
I. Assess the phenotype and activation status of COH06 via flow cytometry, polymerase chain reaction (PCR), and cytokine analysis.
II. Assess T cell activation by flow cytometry and cytokine analysis.
OUTLINE: This is a phase I dose-escalation study of COH06.
Patients receive fludarabine intravenously (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.
After completion of the study treatment, patients are followed for 30 days, every 8 weeks until disease progression, and then annually for 15 years.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 1
Contactos e Locais
Locais de estudo
-
-
California
-
Orange, California, Estados Unidos, 92868
- Chao Family Comprehensive Cancer Center University of California, Irvine
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
-
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)
Exclusion Criteria:
- 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)
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: 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. |
Given IV
Outros nomes:
Correlative studies
Outros nomes:
Given IV
Outros nomes:
Given IV
Outros nomes:
Given COH06 IV
Outros nomes:
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Toxicidades limitantes de dose
Prazo: Dentro de 28 dias após a primeira infusão de COH06
|
Dentro de 28 dias após a primeira infusão de COH06
|
|
|
Incidence of adverse events - CTCAE
Prazo: 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. |
Up to 2 years
|
|
Incidence of adverse events - ASTCT
Prazo: 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. |
Up to 2 years
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Overall Response Rate (ORR)
Prazo: Up to 2 years
|
Overall response rate is calculated as the percent of evaluable subjects that have confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. |
Up to 2 years
|
|
Disease Control Rate (DCR)
Prazo: Up to 2 years
|
Disease control rate is calculated as the percent of evaluable subjects that have confirmed CR or PR or stable disease (SD) per RECIST 1.1 criteria. |
Up to 2 years
|
|
Progression-Free Survival (PFS)
Prazo: 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
|
The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse. |
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
|
|
Overall Survival (OS)
Prazo: From the start of lymphodepletion to death from any cause, assessed up to 2 years
|
The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that patients diagnosed with the disease are still alive. |
From the start of lymphodepletion to death from any cause, assessed up to 2 years
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Miguel Villalona, MD, University of California, Irvine
Publicações e links úteis
Publicações Gerais
- Villalona-Calero MA, Tian L, Li X, Palmer JM, Aceves C, Meisen H, Cortez C, Synold TW, Egelston C, VanDeusen J, Bruno I, Zhang L, Romeu-Bonilla E, Butt O, Forman SJ, Caligiuri MA, Yu J. Interim report on engineered NK cell trial in lung cancer refractory to immune checkpoint inhibitors. JCI Insight. 2025 Feb 4;10(6):e186890. doi: 10.1172/jci.insight.186890.
- Lu T, Ma R, Mansour AG, Bustillos C, Li Z, Li Z, Ma S, Teng KY, Chen H, Zhang J, Villalona-Calero MA, Caligiuri MA, Yu J. Preclinical Evaluation of Off-The-Shelf PD-L1+ Human Natural Killer Cells Secreting IL15 to Treat Non-Small Cell Lung Cancer. Cancer Immunol Res. 2024 Jun 4;12(6):731-743. doi: 10.1158/2326-6066.CIR-23-0324.
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Neoplasias por local
- Neoplasias
- Doenças Respiratórias
- Doenças pulmonares
- Neoplasias do Trato Respiratório
- Neoplasias Torácicas
- Carcinoma Broncogênico
- Neoplasias Brônquicas
- Neoplasias Pulmonares
- Carcinoma pulmonar de células não pequenas
- Produtos químicos orgânicos
- Hidrocarbonetos
- Mustarazas de fosforamida
- Compostos de mostarda de nitrogênio
- Compostos de mostarda
- Hidrocarbonetos, halogenados
- Fosforamidas
- Compostos organofosforos
- Ciclofosfamida
- fludarabina
- Atezolizumab
Outros números de identificação do estudo
- ZotIRB 6431
- P30CA033572 (Concessão/Contrato do NIH dos EUA)
- 20684 (Outro identificador: City of Hope Medical Center)
- NCI-2022-00611 (Identificador de registro: CTRP (Clinical Trial Reporting Program))
- UCI 24-83 (Outro identificador: UCI CFCCC)
- 5R01CA266457-04 (Concessão/Contrato do NIH dos EUA)
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .