이전에 PD-1 및/또는 PD-L1 면역 체크포인트 억제제로 치료한 비소세포폐암 치료를 위한 아테졸리주맙을 포함하거나 포함하지 않는 유전자 조작된 자연 살해(NK) 세포
PD-1/PD-L1에 반응하지 않는 비소세포폐암 환자에서 가용성 IL-15(sIL-15) 및 PD-L1 +/- Atezolizumab을 발현하는 제대혈 자연 살해 세포(CB-NK)의 1상 시험 면역 체크포인트 억제제
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.
연구 개요
상태
상태
정황
정황
개입 / 치료
개입 / 치료
상세 설명
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.
연구 유형
연구 유형
등록 (실제)
등록
단계
단계
- 1단계
연락처 및 위치
연구 장소
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California
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Orange, California, 미국, 92868
- Chao Family Comprehensive Cancer Center University of California, Irvine
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참여기준
자격 기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
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Documented informed consent of the participant and/or legally authorized representative
- Assent, when appropriate, will be obtained per institutional guidelines
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Agreement to allow the use of archival tissue from diagnostic tumor biopsies
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Age >= 18 years
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Eastern Cooperative Oncology Group (ECOG) 0 or 1
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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
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Radiographically demonstrable tumor progression treatment on or after therapy with a PD-1/PD-L1 immune checkpoint inhibitor
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Preserved organ function and recovery of prior drug related toxicities (except alopecia or grade 2 anemia) to grade 1 or better
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No cytotoxic chemotherapy or immunotherapy over the three weeks prior to lymphodepletion
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Histologically confirmed non-small cell lung cancer
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Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1
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Fully recovered from the acute toxic effects (except alopecia) to =< grade 1 to prior anti-cancer therapy
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Absolute neutrophil count (ANC) >= 1,500/mm^3
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Hemoglobin (Hgb) >= 8 g/dl
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Platelets >= 100,000/mm^3
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Total bilirubin =< 1.5 x upper limit of normal (ULN)
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Aspartate aminotransferase (AST) =< 1.5 x ULN
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Alanine aminotransferase (ALT) =< 1.5 x ULN
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Alkaline phosphatase (AP) =< 1.5 x ULN
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Creatinine clearance of >= 60 mL/min per 24-hour urine test or the Cockcroft-Gault formula
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If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (PT) =< 1.5 x ULN
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If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
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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
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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
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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)
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
팔의 수
무기와 개입
참가자 그룹 / 팔참가자 그룹 / 팔 |
개입 / 치료개입 / 치료 |
|---|---|
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실험적: Treatment (fludarabine, cyclophosphamide, COH06, atezolizumab)
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. |
Given IV
다른 이름들:
Correlative studies
다른 이름들:
Given IV
다른 이름들:
Given IV
다른 이름들:
Given COH06 IV
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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용량 제한 독성
기간: 첫 번째 COH06 주입 후 28일 이내
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첫 번째 COH06 주입 후 28일 이내
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Incidence of adverse events - CTCAE
기간: Up to 2 years
|
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. |
Up to 2 years
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Incidence of adverse events - ASTCT
기간: Up to 2 years
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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. |
Up to 2 years
|
2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Overall Response Rate (ORR)
기간: Up to 2 years
|
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. |
Up to 2 years
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Disease Control Rate (DCR)
기간: Up to 2 years
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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. |
Up to 2 years
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Progression-Free Survival (PFS)
기간: 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
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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. |
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
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Overall Survival (OS)
기간: From the start of lymphodepletion to death from any cause, assessed up to 2 years
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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. |
From the start of lymphodepletion to death from any cause, assessed up to 2 years
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공동 작업자 및 조사자
협력자
협력자
수사관
수사관
- 수석 연구원: Miguel Villalona, MD, University of California, Irvine
간행물 및 유용한 링크
일반 간행물
- Villalona-Calero MA, Tian L, Li X, Palmer JM, Aceves C, Meisen H, Cortez C, Synold TW, Egelston C, VanDeusen J, Bruno I, Zhang L, Romeu-Bonilla E, Butt O, Forman SJ, Caligiuri MA, Yu J. Interim report on engineered NK cell trial in lung cancer refractory to immune checkpoint inhibitors. JCI Insight. 2025 Feb 4;10(6):e186890. doi: 10.1172/jci.insight.186890.
- Lu T, Ma R, Mansour AG, Bustillos C, Li Z, Li Z, Ma S, Teng KY, Chen H, Zhang J, Villalona-Calero MA, Caligiuri MA, Yu J. Preclinical Evaluation of Off-The-Shelf PD-L1+ Human Natural Killer Cells Secreting IL15 to Treat Non-Small Cell Lung Cancer. Cancer Immunol Res. 2024 Jun 4;12(6):731-743. doi: 10.1158/2326-6066.CIR-23-0324.
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
연구 시작
기본 완료 (추정된)
기본 완료
연구 완료 (추정된)
연구 완료
연구 등록 날짜
최초 제출
최초 제출
QC 기준을 충족하는 최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
처음 게시됨
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
마지막 업데이트 게시됨
QC 기준을 충족하는 마지막 업데이트 제출
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
기타 연구 ID 번호
- ZotIRB 6431
- P30CA033572 (미국 NIH 보조금/계약)
- 20684 (기타 식별자: City of Hope Medical Center)
- NCI-2022-00611 (레지스트리 식별자: CTRP (Clinical Trial Reporting Program))
- UCI 24-83 (기타 식별자: UCI CFCCC)
- 5R01CA266457-04 (미국 NIH 보조금/계약)
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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