Natural Killer(NK) Cell Combined With Programmed Death-1(PD-1) Antibody as Second Line Therapy for Advanced Driver Mutation Negative Non-small Cell Lung Cancer

NCT03958097 | Completed Phase 2

• 1 other identifier: 19K047-001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

PD-1 antibody has been approved as second line therapy for driven mutation negative non-small cell lung cancer, but overall response rate is only between 15-20%. Basic study found NK cell can enhance anti-tumor ability of PD-L1 antibody. This study evaluates the efficacy and safety of NK cell combined with PD-1 antibody for advanced driven mutation negative non-small cell lung cancer (NSCLC) as second-line therapy.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival(PFS)

  From the random date until the date when the objective disease progression (evaluated by the investigator according to RECIST 1.1) or for any reason (whichever occurs first) is confirmed, based on the intent to treat(ITT) set.

  12 months

Secondary Outcomes (3)

• Overall Response Rate(ORR)

  12 months

• Overall Survival(OS)

  12 months

• Duration of Response(DoR)

  12 months

Other Outcomes (7)

• Disease Control Rate(DCR)

  12 months

• Clinical Benefit Rate(CBR)

  12 months

• Prognostic biomarkers1

  12 months

Study Arms (1)

NK cell combined with PD-L1 antibody

EXPERIMENTAL

Autologous peripheral blood mononuclear cells (PBMCs) are collected by apheresis on D0, then induced into NK cells and infused into the patients 14 days later (D14) as the initial transfusion. There are 3 consecutive transfusion days (D14-D16), total NK cells infused at least 3×10\^9 . 200mg PD-L1 antibody(Sintilimab Injection) will be given on D14, 1 hour after NK cells infusion. NK cells and PD-L1 antibody will be infused every 21 days until disease progression or unacceptable adverse events.

Combination Product: NK cell and PD-1 antibody

Interventions

NK cell and PD-1 antibody COMBINATION_PRODUCT

Each patient enrolled the study will received both NK cell and PD-1 antibody.

NK cell combined with PD-L1 antibody

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (1) Age ≥ 18 years old.
• (2) Locally advanced (IIIB/IIIC phase) or metastatic NSCLC (squamous or non-squamous) confirmed by histological examination.
• (3) Disease progression occurred after platinum-based chemotherapy in the previous line, and measurable lesions existed according to RECIST v1.1.
• (4) Patients must be able to provide fresh or archived tumor tissue and pathology reports. Non-squamous NSCLC must be able to provide a report that is confirmed to be wild-type EGFR by tissue-based assays.
• (5) Eastern Cooperative Oncology Group(ECOG) performance status(PS) ≤ 1.
• (6) The vital organs are fully functional, and the following results are obtained for each laboratory indicator (accepting the results of the examinations made within ≤ 28 days before randomization):
• Cardiac ultrasound indicates a cardiac ejection fraction ≥ 50%; blood oxygen saturation ≥ 90%;
• Absolute neutral cell count (ANC) ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, hemoglobin ≥ 90g/dL;
• Creatinine (Cr) ≤ 2.5 times normal range;
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 times normal range, total bilirubin (TBIL) ≤ 1.5 times normal range.
• (7) No contraindications for apheresis and cell separation.
• (8) Male or female with fertility needs to agree to take effective contraceptive measures during the study period and at least 120 days after the end of medication.
• (9) A written informed consent can be provided and the research requirements are understood and followed.

You may not qualify if:

• (1) Previously received immunological checkpoint inhibitors targeting PD-1, PD-L1 or C ytotoxic T - L ymphocyte A ntigen 4(CTLA-4) and other immunotherapies (including but not limited to interferon or IL-2, chimeric antigen receptor T Cells, vaccines, etc.).
• (2) NSCLC with EGFR gene mutation or ALK gene translocation.
• (3) The toxicity caused by previous anticancer treatment has not recovered to baseline level or returned to stability (except for hair loss, rash, pigmentation or specific laboratory abnormalities).
• (4) A history of severe allergic reactions to other monoclonal antibodies.
• (5) History of interstitial pneumonia, non-infectious pneumonia or uncontrolled systemic diseases, including diabetes, hypertension, and pulmonary fibrosis.
• (6) Clinically severe pericardial effusion.
• (7) Pleural effusion or ascites that is clinically uncontrolled and requires thoracentesis or abdominal puncture drainage within 2 weeks prior to randomization.
• (8) Active pia mater disease or unstable brain metastasis.
• (9) Major surgery, open biopsy or severe traumatic injury was performed ≤ 28 days prior to randomization, or major surgical procedures were expected during the study.
• (10) Other malignant tumors other than NSCLC (except for surgically resected non-melanoma skin cancer, fully treated cervical carcinoma in situ, cured local prostate cancer, fully treated low-grade bladder cancer, Curatively treated breast ductal carcinoma in situ, or a malignant tumor diagnosed 2 years ago, but there is currently no evidence of disease in the absence of treatment ≤ 2 years prior to randomization).
• (11) Severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral treatment, including HIV, hepatitis B virus(HBV), hepatitis C virus(HCV) infection.
• (12) Active autoimmune disease or a history of autoimmune disease but may recur.
• (13) Subjects who require systemic treatment with corticosteroids or other immunosuppressive agents within 14 days prior to randomization.
• (14) Those who have undergone organ transplantation or hematopoietic stem cell transplantation.
• (15) Any live vaccine against infectious diseases (eg, influenza, chickenpox, etc.) was used within 28 days prior to randomization.

Sponsors & Collaborators

• The First Hospital of Jilin University: lead

Study Sites (1)

First Hospital of Jilin University

Changchun, Jilin, 130013, China

Location

Related Publications (2)

• Jia L, Chen N, Chen X, Niu C, Liu Z, Ma K, Wang N, Yang L, Zhao Y, Song W, Lu J, Chen C, Cong X, Wang X, Xu Y, Cui G, Liu Z, Chen R, Li W, Cui J. Sintilimab plus autologous NK cells as second-line treatment for advanced non-small-cell lung cancer previous treated with platinum-containing chemotherapy. Front Immunol. 2022 Dec 8;13:1074906. doi: 10.3389/fimmu.2022.1074906. eCollection 2022.

  PMID: 36569881 RESULT

• Jia L, Chen N, Chen X, Niu C, Liu Z, Ma K, Yang L, Zhao Y, Song W, Lu J, Chen C, Cong X, Wang X, Xu Y, Cui G, Liu Z, Chen R, Yin H, Zhang N, Cui J. Updated overall survival data and predictive biomarkers of autologous NK cells plus Sintilimab as second-line treatment for advanced non-small cell lung cancer. Front Immunol. 2025 May 21;16:1595382. doi: 10.3389/fimmu.2025.1595382. eCollection 2025.

  PMID: 40469279 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: sintilimab plus NK cell

Study Record Dates

• First Submitted: May 20, 2019
• First Posted: May 21, 2019
• Study Start: May 17, 2019
• Primary Completion: October 21, 2020
• Study Completion: October 21, 2021
• Last Updated: April 2, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)