search
Back to results

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

Primary Purpose

Advanced Lung Non-Small Cell Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Recurrent Lung Non-Small Cell Carcinoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Antineoplastic Immune Cell
Atezolizumab
Biospecimen Collection
Cyclophosphamide
Fludarabine
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Lung Non-Small Cell Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • City of Hope Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (fludarabine, cyclophosphamide, COH06, atezolizumab)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.
Dose limiting toxicities

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
March 3, 2022
Last Updated
July 12, 2023
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI), CytoImmune Therapeutics
search

1. Study Identification

Unique Protocol Identification Number
NCT05334329
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 20, 2022 (Actual)
Primary Completion Date
September 30, 2025 (Anticipated)
Study Completion Date
September 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI), CytoImmune Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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 (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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Lung Non-Small Cell Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Recurrent Lung Non-Small Cell Carcinoma, Refractory Lung Non-Small Cell Carcinoma, Stage III Lung Cancer AJCC v8, Stage IIIA Lung Cancer AJCC v8, Stage IIIB Lung Cancer AJCC v8, Stage IIIC Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (fludarabine, cyclophosphamide, COH06, atezolizumab)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Antineoplastic Immune Cell
Other Intervention Name(s)
Anti-cancer Immune Cell, Antineoplastic Immune Cells
Intervention Description
Given COH06 IV
Intervention Type
Biological
Intervention Name(s)
Atezolizumab
Other Intervention Name(s)
MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Biospecimen Collection
Other Intervention Name(s)
Biological Sample Collection, Biospecimen Collected
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
(-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fluradosa
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Incidence of adverse events - CTCAE
Description
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.
Time Frame
Up to 2 years
Title
Incidence of adverse events - ASTCT
Description
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.
Time Frame
Up to 2 years
Title
Dose limiting toxicities
Time Frame
Within 28 days of the first COH06 infusion
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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.
Time Frame
Up to 2 years
Title
Disease Control Rate (DCR)
Description
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.
Time Frame
Up to 2 years
Title
Progression-Free Survival (PFS)
Description
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.
Time Frame
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
Title
Overall Survival (OS)
Description
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.
Time Frame
From the start of lymphodepletion to death from any cause, assessed up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Miguel A Villalona-Calero
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Miguel A. Villalona-Calero
Phone
626-218-8482
Email
mvillalona@coh.org
First Name & Middle Initial & Last Name & Degree
Miguel A. Villalona-Calero

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs