A Cohort Study to Evaluate the Impact of Inactivated Trivalent Influenza Vaccine on the Immunogenicity, Safety and Survival of Non-small Cell Lung Cancer Patients Receiving PD-1 / PD-L1 Inhibitors
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 160
- 试验地点
- 2
- 主要终点
- Titer of neutralization antibody
研究概览
简要总结
This project is to assess the immunogenicity, safety and overall survival impact of intramuscular injection of trivalent influenza vaccine in non-small cell lung cancer (NSCLC) patients with PD-1/PD-L1 inhibitor treatment.
详细描述
Lung cancer is one of the most prevalent cancers in the world. Among them, non-small cell lung cancer (NSCLC) accounts for about 85%. Immune checkpoint inhibitors such as programmed death 1(PD-1) and PD-L1 are new treatments for NSCLC. About 290,000 to 650,000 people die from respiratory illnesses caused by seasonal flu all over the world. Cancer patients are one of the high-risk groups of influenza. Although the United States, Britain, Australia have issued guidelines recommending that cancer patients be vaccinated against influenza every year, due to concerns about the immune effect and safety of flu vaccination for cancer patients, multiple countries including China have not included cancer patients into priority influenza vaccination populations. Therefore, how to further prove the immunogenicity and safety of influenza vaccine in NSCLC patients is the key to promote influenza vaccines in NSCLC patients.
This study will recruit 130 patients with NSCLC who have been treated with PD-1 / PD-L1 inhibitors for 6 months or more and 30 healthy participants. Among them, 100 NSCLC patients and 30 healthy participants will be intramuscularly inactivated with a trivalent influenza vaccine during the influenza seasons 2020-21 and 2021-22. Vaccinated participants' peripheral blood samples were collected at day0, 12 hours, day1, 2, 7, 21, 30, 60 and 6 months after vaccination. The influenza specific antibody titers, inflammatory chemokines and cytokines, antibody-dependent cellular cytotoxicity (ADCC) activity, T lymphocytes activity and the proportions of different T cells subgroups will be measured to evaluate the participants' immune response to the vaccine. In addition, for the subjects receiving the vaccine, the study will also group by age to compare the differences in immune effects between subjects aged 18-65 and subjects over 65.
At last, this project will compare immune-related adverse events (irAEs) that occurred after receiving PD-1 / PD-L1 inhibitor therapy and survival time between NSCLC patients who receive influenza vaccine and those who do not receive influenza vaccine.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •NSCLC patients were diagnosed with clear pathological classification and receive PD-1 / PD-L1 inhibitor treatment during this project.
- •NSCLC patients have the exact start and end time of PD-1 / PD-L1 inhibitor and / or the vaccination time and follow-up information.
- •The healthy participants are not in an immunosuppressive state, such as cancer, HIV, autoimmune diseases, and long-term use of immunosuppressive drugs.
- •The healthy participants have exact vaccination time.
- •All participants have complete clinical and laboratory diagnostic data.
- •All participants are 18-75 years, regardless of gender.
- •All participants have agreed and signed the consent form before enrollment.
排除标准
- •Patients with unclear diagnosis of lung cancer were excluded.
- •Patients with incomplete clinical data or incomplete follow-up records.
- •Patients without signed informed consent.
- •Patient has received blood transfusion within three months.
- •Patients with HIV, Hepatitis B and Hepatitis C infections.
研究组 & 干预措施
Vaccinated NSCLC group
This group contains 100 NSCLC patients receiving PD-1/PD-L1 inhibitors for more than 6 months, who will be intramuscularly injected one dose of inactivated trivalent influenza vaccine in influenza seasons 2020-21 or 2021-22 (November-May).
干预措施: PD-1/PD-L1 inhibitors (Drug)
Vaccinated NSCLC group
This group contains 100 NSCLC patients receiving PD-1/PD-L1 inhibitors for more than 6 months, who will be intramuscularly injected one dose of inactivated trivalent influenza vaccine in influenza seasons 2020-21 or 2021-22 (November-May).
干预措施: Inactivated trivalent influenza vaccine (Biological)
Vaccinated Health group
This group contains 30 healthy participants without immunosuppressive diseases, who will be intramuscularly injected one dose of inactivated trivalent influenza vaccine in influenza seasons 2020-21 or 2021-22 (November-May).
干预措施: Inactivated trivalent influenza vaccine (Biological)
Unvaccinated NSCLC group
This group contains 30 NSCLC patients receiving PD-1/PD-L1 inhibitors for more than 6 months without intramuscular injection of any inactivated trivalent influenza vaccine in influenza seasons 2020-21 or 2021-22 (November-May).
干预措施: PD-1/PD-L1 inhibitors (Drug)
结局指标
主要结局
Titer of neutralization antibody
时间窗: Month 6 after vaccination
Titer of neutralization antibody is measured by neutralization test.
The numbers and proportions of T lymphocyte subpopulations in peripheral blood
时间窗: Month 6 after vaccination
The numbers and proportions of CD4+ T cells, CD8+ T cells, naïve T cells and effector memory T cells in peripheral blood are measured by multiple flow cytometry.
Antibody-dependent cellular cytotoxicity (ADCC)
时间窗: Month 6 after vaccination
The ADCC activities of NK-92 cells cultured by the sera collected from vaccinated participants are measured by lactic acid dehydrogenase (LDH) release of A549 cells infected by H1N1 and H3N2.
Titers of anti-nucleoprotein(NP) or anti-hemagglutinin(HA) antibody (IgG and IgM)
时间窗: Day 30 after vaccination
The titers of anti-HA IgG and IgM antibodies ,and anti-NP IgG and IgM antibodies are measured by enzyme linked immunosorbent assay (ELISA).
Immune-related adverse events (irAEs)
时间窗: June 2020- June 2023
The performances and the grades of irAEs according to Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0) and their correlation with vaccination.
Progression-free Survival (PFS)
时间窗: June 2020- June 2023 (3 year)
PFS is calculated as the time from from PD-1/PD-L1 inhibitor starting to the disease progression or the death from any cause.
Multiple chemokine and cytokine levels in peripheral blood
时间窗: Day 2 after vaccination
IFN-γ, IL-1β, IL-2,IL-3,IL-4,IL-5,IL-6,IL-8 (CXCL8),IL-9,IL-10,IL-11,IL-12,IL-13,GM-CSF,TNF-α, IP-10 (CXCL10), MCP-1 (CCL2), and TARC (CCL17) in peripheral blood are measured by cytometry bead assay.
Peripheral T cell activation and proliferation
时间窗: Month 6 after vaccination
The CD3, CD4, CD8 and CD69 expressions and cell count of peripheral T cells are measured by multiple flow cytometry upon carboxyfluorescein succinimidyl amino ester (CFSE) labeling and anti-CD3/28 beads activation.
Overall Survival (OS)
时间窗: June 2020- June 2023 (3 year)
OS is calculated as the time from PD-1/PD-L1 inhibitor starting to the death from any cause.
次要结局
- Objective Response Rate (ORR)(June 2020- June 2023 (3 year))
- Disease Control Rate (DCR)(June 2020- June 2023 (3 year))
- Time to Treatment Failure (TFF)(June 2020- June 2023 (3 year))
研究者
Caicun Zhou
Professor
Shanghai Pulmonary Hospital, Shanghai, China