Umbilical CB-NK Expressing sIL-15 & PD-L1 +/- Atezolizumab in NSCLC Pts Refractory to PD-1/PD-L1
Phase I 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 Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Study Type
Study Type
Enrollment (Estimated)
Enrollment
Phase
Phase
- Phase 1
Contacts and Locations
Study Contact
Study Contact
- Name: Chao Family Comprehensive Cancer Center University of California, Irvine
- Phone Number: 1-877-827-8839
- Email: ucstudy@uci.edu
Study Contact Backup
- Name: University of California Irvine Medical Center
Study Locations
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-
California
-
Orange, California, United States, 92868
- Chao Family Comprehensive Cancer Center University of California, Irvine
-
Contact:
- Miguel Villalona, MD
- Phone Number: 877-827-8839
- Email: ucstudy@uci.edu
-
-
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Documented informed consent of the participant
- Agreement to allow the use of archival tissue from diagnostic tumor biopsies
- Age: ≥ 18 years
- ECOG 0 to 1
- NSCLC patients with advanced, metastatic, or recurrent disease, previously treated with a PD-1 or PDL-1 immune checkpoint inhibitor, either as single agent or in combination with chemotherapy or other immunotherapy or experimental agents
- Radiographically demonstrated tumor progression on or after PD-1/PD-L1 immune checkpoint inhibitor treatment
- 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 RECIST criteria 1.1
- Fully recovered from the acute toxic effects (except alopecia) to ≤ Grade 1 to prior anti- cancer therapy
- Cardiac ejection fraction ≥ 50% and no clinically significant EKG findings (same criteria must also be met for patients selected for a second course of therapy).
- ANC ≥ 1,500/mm^3
- Hgb ≥ 8 g/dl
- Platelets ≥ 100,000/mm3
- Total bilirubin ≤ 1.5 X ULN
- AST ≤ 1.5 x ULN
- ALT ≤ 1.5 x ULN
- AP ≤ 1.5 x ULN
- Creatinine within 1.5 times the normal upper limit or with a creatinine clearance of ≥ 50 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 HIV Ag/Ab combo, HCV*, active HBV (Surface Antigen Negative)
*If positive, Hepatitis C 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 MRI scans.
- Adults lacking capacity to give their informed consent will be excluded from participation
- Cardiac ejection fraction < 50%
- 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).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Experimental: NK-102 +/- Atezolizumab
Study participants will be assigned to a protocol-specified treatment dose level.
|
Given IV
Other Names:
Given IV
|
What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Optimal biological dose (OBD) of NK-102 as monotherapy and when given in combination with Atezolizumab
Time Frame: Up to 16 weeks
|
Determination of the optimal biological dose (OBD) will be utilized to evaluate the safety and tolerability of NK-102 or when NK-102 is given in combination with Atezolizumab.
|
Up to 16 weeks
|
|
Detection and Measurement of persistence in the peripheral blood to assess cellular kinetics of NK-102
Time Frame: Samples will be collected on day 28
|
The number of NK-102 cells in blood will be measured to assess the persistence of infused NK-102 cells after administration.
|
Samples will be collected on day 28
|
Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Overall Response Rate (ORR)
Time Frame: Up to 48 months
|
Overall response rate (ORR) is defined as confirmed complete response (CR) and partial response (PR).
Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1): Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions.
ORR = CR + PR
|
Up to 48 months
|
|
Disease Control Rate (DCR)
Time Frame: Up to 48 months
|
Disease Control Rate (DCR) is defined as confirmed complete response (CR), partial response (PR) and Stable Disease.
Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1): Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions; Stable Disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
DCR = CR + PR + SD
|
Up to 48 months
|
|
Response Duration
Time Frame: Up to 48 months
|
The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
|
Up to 48 months
|
|
Disease Control Duration
Time Frame: Up to 48 months
|
Stable disease is measured from the start of the treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started, including the baseline measurements.
|
Up to 48 months
|
|
Progression Free Survival (PFS) Rate
Time Frame: At 6 months and 1 year post NK-102 cell infusion
|
Progression will be evaluated in this study using the RECIST guideline (version 1.1)
|
At 6 months and 1 year post NK-102 cell infusion
|
|
Overall Survival (OS) Rate
Time Frame: At 6 months and 1 year post NK-102 cell infusion.
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Survival rate of participants who received NK-102
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At 6 months and 1 year post NK-102 cell infusion.
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Collaborators and Investigators
Sponsor
Sponsor
Collaborators
Collaborators
Investigators
Investigators
- Principal Investigator: Miguel Villalona, MD, Chao Family Comprehensive Cancer Center
Study record dates
Study Major Dates
Study Start (Estimated)
Study Start
Primary Completion (Estimated)
Primary Completion
Study Completion (Estimated)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Actual)
First Posted
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Site
- Neoplasms
- Respiratory Tract Diseases
- Lung Diseases
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Antineoplastic Agents
- Molecular Mechanisms of Pharmacological Action
- Atezolizumab
Other Study ID Numbers
Other Study ID Numbers
- 6431
- UCI 24-83 (Other Identifier: UCI CFCCC)
- 5R01CA266457-04 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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