Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Recurrence

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immune Checkpoint Inhibitors

Atezolizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

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.

Antineoplastic Immune Cell

Biospecimen Collection

Miguel A Villalona-Calero

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.

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.

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

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

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.

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.

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.

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.

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.

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.

National Cancer Institute (NCI)

CytoImmune Therapeutics

City of Hope Medical Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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	NCT05334329	Advanced Lung N... Metastatic Lung... Recurrent Lung ... Refractory Lung... Stage III Lung ... Stage IIIA Lung... Stage IIIB Lung... Stage IIIC Lung... Stage IV Lung C... Stage IVA Lung ... Stage IVB Lung ...	Antineoplastic ... Atezolizumab Biospecimen Col... Cyclophosphamid... Fludarabine	18 Years -	City of Hope Medical Center
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	NCT05334329	Advanced Lung N... Metastatic Lung... Recurrent Lung ... Refractory Lung... Stage III Lung ... Stage IIIA Lung... Stage IIIB Lung... Stage IIIC Lung... Stage IV Lung C... Stage IVA Lung ... Stage IVB Lung ...	Antineoplastic ... Atezolizumab Biospecimen Col... Cyclophosphamid... Fludarabine	18 Years -	City of Hope Medical Center

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