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

Not Applicable

Not yet recruiting

• Conditions: Non-small Cell Lung Cancer; NSCLC; Lung Cancer, Non-small Cell; Lung Cancer
• Interventions: Drug: NK-102; Drug: Atezolizumab

• Registration Number: NCT07053007
• Lead Sponsor: University of California, Irvine

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-06-30
• Study First Submitted QC: 2025-06-30
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-07
• Study First Posted: 2025-07-08
• Last Update Posted: 2025-07-10
• Study Start: 2025-09-01
• Primary Completion: 2027-12
• Study Completion: 2029-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 9

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NK-102 +/- Atezolizumab	NK-102	Study participants will be assigned to a protocol-specified treatment dose level.
NK-102 +/- Atezolizumab	Atezolizumab	Study participants will be assigned to a protocol-specified treatment dose level.

Primary Outcome Measures

Name	Time	Method
Optimal biological dose (OBD) of NK-102 as monotherapy and when given in combination with Atezolizumab	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.
Detection and Measurement of persistence in the peripheral blood to assess cellular kinetics of NK-102	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.

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	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
Disease Control Rate (DCR)	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
Response Duration	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).
Disease Control Duration	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.
Progression Free Survival (PFS) Rate	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)
Overall Survival (OS) Rate	At 6 months and 1 year post NK-102 cell infusion.	Survival rate of participants who received NK-102

Trial Locations

Locations (1)

Chao Family Comprehensive Cancer Center University of California, Irvine; 🇺🇸 Orange, California, United States