Non-small Cell Lung CancerPhase 2NCT03958097
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
A Phase 2 study testing NK cell and PD-1 antibody in people with Non-small Cell Lung Cancer, run by The First Hospital of Jilin University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer
- What is being tested?
- NK cell and PD-1 antibody
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 17 May 2019to 21 Oct 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- (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):
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- 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.
Who cannot join
- (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.
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- (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.
- (16) Meet any of the following cardiovascular disease criteria:
- Evidence of acute or positive myocardial ischemia
- There are currently symptomatic pulmonary embolisms
- Acute myocardial infarction occurred within ≤6 months before randomization.
- Has reached the New York Heart Association grading standard (see Appendix 5) 3 or 4 before randomization ≤ 6 months Grade of heart failure.
- A ≥2 grade ventricular arrhythmia occurred within ≤6 months before randomization.
- A cerebrovascular accident (CVA) or transient ischemic attack (TIA) occurred within ≤6 months before randomization.
- (17) Pregnant and lactating women.
- (18) If the patient is unable to follow the study procedures, limitations, and requirements, the investigator believes that the patient is not allowed to participate in the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pilot Study of NK Cell Combined With PD-1 Antibody as Second Line Therapy for Advanced Driver Mutation Negative Non-small Cell Lung Cancer
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.
Read the detailed description
The incidence of non-small cell lung cancer is high, and most patients are in advanced stage at the time of diagnosis, and the overall prognosis is poor. Currently, patients with advanced non-small cell lung cancer are treated individually according to the molecular and histological features of the tumor. For patients with negative driver mutation in epidermal growth factor receptor(EGFR), anaplastic lymphoma kinase(ALK),ROS proto-oncogene1(ROS1), v-raf murine sarcoma viral oncogene homolog B1(BRAF) and other driving genes, platinum-based dual chemotherapy combined with PD-1/PD-L1 monoclonal antibody is recommended for first-line treatment. In patients who have not used PD-1/PD-L1 antibody in first-line therapy, the second-line treatment regimen is the first choice for the recommended single-agent PD-1/PD-L1 antibody. However, the current efficacy of PD-1/PD-L1 antibody for second-line treatment of advanced non-small cell lung cancer is limited, only between 15-20%. NK cells secrete interferon(IFN) to promote the expression of PD-L1 in tumor cells and enhance the role of PD-1 inhibitors. At the same time, PD-1 antibodies can bind to NK cell surface PD-1, prevent NK cell depletion, and enhance NK cell anti-tumor. Therefore, the application of NK cells combined with PD-1 antibody in the treatment of patients with advanced non-small cell lung cancer may achieve better results.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- NK cell and PD-1 antibody
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NK cell and PD-1 antibodyCombination product
Each patient enrolled the study will received both NK cell and PD-1 antibody.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Combination Product: NK cell and PD-1 antibody |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (3)
Overall Response Rate(ORR)
The proportion of patients with complete response(CR) or partial response(PR) (evaluated by the investigator according to RECIST 1.1), based on the ITT set.
Measured: 12 months
Overall Survival(OS)
The time from the random date to the date of death for any reason, based on the ITT population.
Measured: 12 months
Duration of Response(DoR)
The time from the first confirmed objective remission to recurrence (evaluated by the investigator according to RECIST 1.1) or for any reason, whichever occurs first.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2019
- Study start17 May 2019
- Primary completion21 Oct 2020
- Study completion21 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- sintilimab plus NK cell
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- The First Hospital of Jilin University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03958097
- Sponsor's protocol ID
- 19K047-001
- Status last verified
- Mar 2024
- First submitted
- 20 May 2019
- Last updated
- 2 Apr 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36569881Jia 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.
PubMed 40469279
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of NK Cell Combined With PD-1 Antibody as Second Line Therapy for Advanced Driver Mutation Negative Non-small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT03958097
- Acronym / sponsor ID
- 19K047-001
- Conditions
- Non-small Cell Lung Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- The First Hospital of Jilin UniversityUniversity, hospital or other
- Study start
- 17 May 2019 (actual)
- Primary completion
- 21 Oct 2020 (actual)
- Study completion
- 21 Oct 2021 (actual)
- First posted
- 21 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The incidence of non-small cell lung cancer is high, and most patients are in advanced stage at the time of diagnosis, and the overall prognosis is poor. Currently, patients with advanced non-small cell lung cancer are treated individually according to the molecular and histological features of the tumor. For patients with negative driver mutation in epidermal growth factor receptor(EGFR), anaplastic lymphoma kinase(ALK),ROS proto-oncogene1(ROS1), v-raf murine sarcoma viral oncogene homolog B1(BRAF) and other driving genes, platinum-based dual chemotherapy combined with PD-1/PD-L1 monoclonal antibody is recommended for first-line treatment. In patients who have not used PD-1/PD-L1 antibody in first-line therapy, the second-line treatment regimen is the first choice for the recommended single-agent PD-1/PD-L1 antibody. However, the current efficacy of PD-1/PD-L1 antibody for second-line treatment of advanced non-small cell lung cancer is limited, only between 15-20%. NK cells secrete interferon(IFN) to promote the expression of PD-L1 in tumor cells and enhance the role of PD-1 inhibitors. At the same time, PD-1 antibodies can bind to NK cell surface PD-1, prevent NK cell depletion, and enhance NK cell anti-tumor. Therefore, the application of NK cells combined with PD-1 antibody in the treatment of patients with advanced non-small cell lung cancer may achieve better results.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- sintilimab plus NK cell
| Arm | Type | Receives |
|---|---|---|
| NK cell combined with PD-L1 antibody | Experimental | Combination Product: NK cell and PD-1 antibodyAutologous 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- (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.
Key exclusion criteria (24 listed)
- (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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NK cell and PD-1 antibodyEach patient enrolled the study will received both NK cell and PD-1 antibody. | Combination product | NK cell combined with PD-L1 antibody |
Primary outcome
Progression Free Survival(PFS)
Time frame: 12 months
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.
3 secondary outcomes
Overall Response Rate(ORR)
Time frame: 12 months
Overall Survival(OS)
Time frame: 12 months
Duration of Response(DoR)
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2024.
- Results publication: PubMed 36569881Jia 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.
- Derived from this study: PubMed 40469279Jia 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NK cell and PD-1 antibody in people with Non-small Cell Lung Cancer, run by The First Hospital of Jilin University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival(PFS) (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03958097, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2024.