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Genetisch gemanipuleerde Natural Killer (NK)-cellen met of zonder atezolizumab voor de behandeling van niet-kleincellige longkanker die eerder is behandeld met PD-1 en/of PD-L1 Immune Checkpoint-remmers

1 oktober 2026 bijgewerkt door: Miguel Angel Villalona, University of California, Irvine

Fase 1-onderzoek met Natural Killer Cells (CB-NK) uit navelstrengbloed die oplosbaar IL-15 (sIL-15) en PD-L1 +/- Atezolizumab tot expressie brengen bij patiënten met niet-kleincellige longkanker die ongevoelig zijn voor PD-1/PD-L1 Immuun Checkpoint-remmers

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.

Studie Overzicht

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

6

Fase

  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

    • California
      • Orange, California, Verenigde Staten, 92868
        • Chao Family Comprehensive Cancer Center University of California, Irvine

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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)

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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

Andere namen:
  • Cytoxaan
  • CTX
  • (-)-cyclofosfamide
  • 2H-1,3,2-Oxazafosforine, 2-[bis(2-chloorethyl)amino]tetrahydro-, 2-oxide, monohydraat
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Clafeen
  • CP monohydraat
  • CYCLO-cel
  • Cycloblastine
  • Cyclofosfam
  • Cyclofosfamide-monohydraat
  • Cyclofosfamidum
  • Cyclofosfan
  • Cyclofosfaan
  • Cyclofosfanum
  • Cyclostine
  • Cytofosfan
  • Cytofosfaan
  • Fosfaseron
  • Genoxal
  • Genuxaal
  • Ledoxine
  • Mitoxan
  • Neosar
  • Opwekken
  • Syklofosfamide
  • WR-138719

Correlative studies

Andere namen:
  • Biologische monsterverzameling
  • Biospecimen verzameld

Given IV

Andere namen:
  • Fluradosa

Given IV

Andere namen:
  • Tecentriq
  • MPDL3280A
  • RO5541267
  • RG7446
  • MPDL 3280A
  • MPDL 328OA
  • MPDL-3280A
  • MPDL328OA

Given COH06 IV

Andere namen:
  • Immuuncel tegen kanker
  • Antineoplastische immuuncellen

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Dosisbeperkende toxiciteiten
Tijdsspanne: Binnen 28 dagen na de eerste COH06-infusie
Binnen 28 dagen na de eerste COH06-infusie
Incidence of adverse events - CTCAE
Tijdsspanne: 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
Tijdsspanne: 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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Overall Response Rate (ORR)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Onderzoekers

  • Hoofdonderzoeker: Miguel Villalona, MD, University of California, Irvine

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

20 juli 2022

Primaire voltooiing (Geschat)

30 november 2028

Studie voltooiing (Geschat)

30 november 2028

Studieregistratiedata

Eerst ingediend

3 maart 2022

Eerst ingediend dat voldeed aan de QC-criteria

12 april 2022

Eerst geplaatst (Werkelijk)

19 april 2022

Updates van studierecords

Laatste update geplaatst (Werkelijk)

6 oktober 2026

Laatste update ingediend die voldeed aan QC-criteria

1 oktober 2026

Laatst geverifieerd

1 oktober 2026

Meer informatie

Termen gerelateerd aan deze studie

Andere studie-ID-nummers

  • ZotIRB 6431
  • P30CA033572 (Subsidie/contract van de Amerikaanse NIH)
  • 20684 (Andere identificatie: City of Hope Medical Center)
  • NCI-2022-00611 (Register-ID: CTRP (Clinical Trial Reporting Program))
  • UCI 24-83 (Andere identificatie: UCI CFCCC)
  • 5R01CA266457-04 (Subsidie/contract van de Amerikaanse NIH)

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Ja

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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