Umbilical CB-NK Expressing sIL-15 & PD-L1 +/- Atezolizumab in NSCLC Pts Refractory to PD-1/PD-L1

July 7, 2025 updated by: Miguel Angel Villalona, University of California, Irvine

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

This is a Phase 1 dose escalation clinical trial determining the maximum tolerated dose of NK-102 in subjects with advanced, metastatic, or recurrent non-small cell lung cancer (NSCLC) (previously treated with PD1 and/or PD-L1 immune checkpoint inhibitors) as monotherapy or in combination with atezolizumab.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

9

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

    • California
      • Orange, California, United States, 92868
        • Chao Family Comprehensive Cancer Center University of California, Irvine
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NK-102 +/- Atezolizumab
Study participants will be assigned to a protocol-specified treatment dose level.
Given IV
Other Names:
  • Tecentriq
Given IV

What is the study measuring?

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

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.
Survival rate of participants who received NK-102
At 6 months and 1 year post NK-102 cell infusion.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Collaborators

Investigators

  • Principal Investigator: Miguel Villalona, MD, Chao Family Comprehensive Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2025

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2029

Study Registration Dates

First Submitted

June 30, 2025

First Submitted That Met QC Criteria

June 30, 2025

First Posted (Actual)

July 8, 2025

Study Record Updates

Last Update Posted (Actual)

July 10, 2025

Last Update Submitted That Met QC Criteria

July 7, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

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)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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