- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT05334329
Geneticky upravené buňky přirozeného zabíječe (NK) s atezolizumabem nebo bez něj pro léčbu nemalobuněčného karcinomu plic dříve léčeného inhibitory imunitního kontrolního bodu PD-1 a/nebo PD-L1
Fáze 1 studie s přirozenými zabíječskými buňkami z pupečníkové krve (CB-NK) exprimujícími rozpustný IL-15 (sIL-15) a PD-L1 +/- atezolizumab u pacientů s nemalobuněčným karcinomem plic refrakterních na PD-1/PD-L1 Inhibitory imunitního kontrolního bodu
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.
Přehled studie
Postavení
Podmínky
- Metastatický nemalobuněčný karcinom plic
- Refrakterní nemalobuněčný karcinom plic
- Fáze IVA rakoviny plic AJCC v8
- Stádium IVB rakoviny plic AJCC v8
- Fáze III rakoviny plic AJCC v8
- Fáze IV rakoviny plic AJCC v8
- Stádium IIIA rakoviny plic AJCC v8
- Stádium IIIB rakoviny plic AJCC v8
- Stádium IIIC rakoviny plic AJCC v8
- Pokročilý nemalobuněčný karcinom plic
- Recidivující nemalobuněčný karcinom plic
Detailní popis
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.
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 1
Kontakty a umístění
Studijní místa
-
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California
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Orange, California, Spojené státy, 92868
- Chao Family Comprehensive Cancer Center University of California, Irvine
-
-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
-
Documented informed consent of the participant and/or legally authorized representative
- Assent, when appropriate, will be obtained per institutional guidelines
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Agreement to allow the use of archival tissue from diagnostic tumor biopsies
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Age >= 18 years
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Eastern Cooperative Oncology Group (ECOG) 0 or 1
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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
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Radiographically demonstrable tumor progression treatment on or after therapy with a PD-1/PD-L1 immune checkpoint inhibitor
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Preserved organ function and recovery of prior drug related toxicities (except alopecia or grade 2 anemia) to grade 1 or better
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No cytotoxic chemotherapy or immunotherapy over the three weeks prior to lymphodepletion
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Histologically confirmed non-small cell lung cancer
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Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1
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Fully recovered from the acute toxic effects (except alopecia) to =< grade 1 to prior anti-cancer therapy
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Absolute neutrophil count (ANC) >= 1,500/mm^3
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Hemoglobin (Hgb) >= 8 g/dl
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Platelets >= 100,000/mm^3
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Total bilirubin =< 1.5 x upper limit of normal (ULN)
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Aspartate aminotransferase (AST) =< 1.5 x ULN
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Alanine aminotransferase (ALT) =< 1.5 x ULN
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Alkaline phosphatase (AP) =< 1.5 x ULN
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Creatinine clearance of >= 60 mL/min per 24-hour urine test or the Cockcroft-Gault formula
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If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (PT) =< 1.5 x ULN
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If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
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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
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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
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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)
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: 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
Ostatní jména:
Correlative studies
Ostatní jména:
Given IV
Ostatní jména:
Given IV
Ostatní jména:
Given COH06 IV
Ostatní jména:
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Toxicita omezující dávku
Časové okno: Do 28 dnů od první infuze COH06
|
Do 28 dnů od první infuze COH06
|
|
|
Incidence of adverse events - CTCAE
Časové okno: 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
Časové okno: 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
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Overall Response Rate (ORR)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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
|
Spolupracovníci a vyšetřovatelé
Sponzor
Spolupracovníci
Vyšetřovatelé
- Vrchní vyšetřovatel: Miguel Villalona, MD, University of California, Irvine
Publikace a užitečné odkazy
Obecné publikace
- 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.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
- Novotvary podle místa
- Novotvary
- Nemoci dýchacích cest
- Plicní onemocnění
- Novotvary dýchacího traktu
- Novotvary hrudníku
- Karcinom, Bronchogenní
- Bronchiální novotvary
- Novotvary plic
- Karcinom, nemalobuněčné plíce
- Organické chemikálie
- Uhlovodíky
- Fosforamidové hořčice
- Sloučeniny hořčice dusíku
- Hořčičné sloučeniny
- Uhlovodíky, halogenované
- Fosforamidy
- Organofosforové sloučeniny
- Cyklofosfamid
- Fludarabine
- Atezolizumab
Další identifikační čísla studie
- ZotIRB 6431
- P30CA033572 (Grant/smlouva NIH USA)
- 20684 (Jiný identifikátor: City of Hope Medical Center)
- NCI-2022-00611 (Identifikátor registru: CTRP (Clinical Trial Reporting Program))
- UCI 24-83 (Jiný identifikátor: UCI CFCCC)
- 5R01CA266457-04 (Grant/smlouva NIH USA)
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
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