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Advanced Lung Non-Small Cell CarcinomaPhase 1NCT05334329

Genetically Engineered Natural Killer (NK) Cells With or Without Atezolizumab for the Treatment of Non-small Cell Lung Cancer Previously Treated With PD-1 and/or PD-L1 Immune Checkpoint Inhibitors

A Phase 1 study testing Antineoplastic Immune Cell, Atezolizumab and Biospecimen Collection in people with Advanced Lung Non-Small Cell Carcinoma and Metastatic Lung Non-Small Cell Carcinoma, run by University of California, Irvine at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Antineoplastic Immune Cell, Atezolizumab and Biospecimen Collection
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
20 Jul 2022to 30 Nov 2028
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Chao Family Comprehensive Cancer Center University of California, Irvine

    Orange, California, 92868

Other trials in United States

About this study

Official title: 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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
Antineoplastic Immune Cell, Atezolizumab, Biospecimen Collection, Cyclophosphamide, Fludarabine
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Antineoplastic Immune CellBiological

    Also called Anti-cancer Immune Cell, Antineoplastic Immune Cells

    Given COH06 IV

  • AtezolizumabBiological

    Also called MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A

    Given IV

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected

    Correlative studies

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • FludarabineDrug

    Also called Fluradosa

    Given IV

Study groups in NCT05334329
Study groupRoleWhat they receive
Treatment (fludarabine, cyclophosphamide, COH06, atezolizumab)ExperimentalPatients 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.
Receives: Biological: Antineoplastic Immune Cell; Biological: Atezolizumab; Procedure: Biospecimen Collection; Drug: Cyclophosphamide; Drug: Fludarabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of adverse events - CTCAE

    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.

    Measured: Up to 2 years

  2. Incidence of adverse events - ASTCT

    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.

    Measured: Up to 2 years

  3. Dose limiting toxicities

    Measured: Within 28 days of the first COH06 infusion

Secondary outcomes (4)

  1. Overall Response Rate (ORR)

    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.

    Measured: Up to 2 years

  2. Disease Control Rate (DCR)

    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.

    Measured: Up to 2 years

  3. Progression-Free Survival (PFS)

    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.

    Measured: 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

  4. Overall Survival (OS)

    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.

    Measured: From the start of lymphodepletion to death from any cause, assessed up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Apr 2022
  2. Study start20 Jul 2022
  3. Primary completion30 Nov 2028 (estimated)
  4. Study completion30 Nov 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05334329
Sponsor's protocol ID
ZotIRB 6431
Other IDs
NCI-2022-00611, 20684, P30CA033572, 5R01CA266457-04, UCI 24-83
Status last verified
Oct 2026
First submitted
3 Mar 2022
Last updated
6 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 39903538

  • 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.

    PubMed 38572955

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Antineoplastic Immune Cell, Atezolizumab and Biospecimen Collection in people with Advanced Lung Non-Small Cell Carcinoma and Metastatic Lung Non-Small Cell Carcinoma, run by University of California, Irvine at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 6 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events - CTCAE (time frame: Up to 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05334329, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2026.

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