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

University of California Irvine (UCI)

Status and phase

Begins enrollment this month

Phase 1

Conditions

Non-small Cell Lung Cancer

Lung Cancer

Lung Cancer, Non-small Cell

NSCLC

Treatments

Drug: Atezolizumab

Drug: NK-102

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT07053007

5R01CA266457-04 (U.S. NIH Grant/Contract)

UCI 24-83 (Other Identifier)

6431

Details and patient eligibility

About

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.

Enrollment

9 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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).