Prospective Study of Changes in Peripheral Blood Effector Tumor Antigen-Specific T Cells for Predicting Efficacy of Chemoimmunotherapy in Non-Small Cell Lung Cancer
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 80
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
The goal of this observational study is to explore whether changes in peripheral blood effector tumor antigen-specific T cells (ETASTs) can predict treatment outcomes in patients with advanced non-small cell lung cancer (NSCLC) receiving chemoimmunotherapy. The study aims to:
- Evaluate the relationship between ΔETAST levels (baseline to cycle 2) and progression-free survival
- Compare the predictive performance of ΔETASTs with traditional biomarkers (PD-L1, TMB)
- Assess whether ΔETASTs can identify patients more likely to benefit from PD-1 inhibitor plus chemotherapy
Participants will:
- Provide peripheral blood samples at baseline and after cycle 2 of treatment
- Undergo ETAST quantification using the CTT-NanoDT technology with TATAN nanoparticles
- Have standard tumor assessments every 2 cycles according to RECIST 1.1 criteria
- Be followed for progression-free survival and overall survival up to 24 months
详细描述
Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases globally. While immune checkpoint inhibitors (ICIs), particularly PD-1/PD-L1 inhibitors combined with platinum-based chemotherapy, have become standard first-line therapy for advanced NSCLC, only a subset of patients achieve clinical benefit. Current biomarkers including PD-L1 expression and tumor mutational burden (TMB) have limited predictive accuracy, creating an urgent need for more reliable biomarkers.
Tumor antigen-specific T cells (TASTs) are the actual effectors in ICI therapy, and successful ICI response depends on reactivation of these cells. However, detection of circulating tumor antigen-specific T cells (CTASTs) has been technically challenging due to their low frequency and heterogeneity in peripheral blood.
This study utilizes a novel Circulating Tumor-Specific T Cell Nanodetection Technology (CTT-NanoDT) developed by the research team. The technology employs Tumor Antigen-specific T cell Activating Nanoparticles (TATAN) loaded with whole tumor cell components to specifically activate and quantify effector TASTs (ETASTs) in peripheral blood.
Study Design:
This is a prospective, single-center, observational cohort study enrolling 80 patients with stage IIIB-IV NSCLC receiving standard PD-1 inhibitor plus platinum-based chemotherapy. Peripheral blood samples (5 mL) will be collected at two time points: baseline (T0, within 1 day before treatment initiation) and after completion of cycle 2 (T1, day 21 of cycle 2).
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed stage IIIB-IV non-small cell lung cancer (NSCLC)
- •Planned to receive PD-1 inhibitor combined with platinum-based chemotherapy (e.g., pembrolizumab + pemetrexed/carboplatin)
- •Age 18-80 years
- •ECOG performance status 0-1
- •Expected survival ≥12 weeks
- •Adequate bone marrow function: ANC ≥1.5×10⁹/L, PLT ≥100×10⁹/L
- •Adequate hepatorenal function: Cr ≤1.5×ULN, ALT/AST ≤2.5×ULN
- •At least one measurable lesion per RECIST 1.1 criteria
- •Able to provide informed consent and comply with study procedures including serial blood sampling and imaging follow-up
排除标准
- •No measurable disease per RECIST 1.1 criteria
- •Tumor emergencies requiring immediate intervention (spinal cord compression, superior vena cava syndrome)
- •Active untreated central nervous system metastases or leptomeningeal disease
- •Prior treatment with immune checkpoint inhibitors within 4 weeks before enrollment
- •Chronic use of immunosuppressive agents (e.g., corticosteroids >10 mg/day prednisone equivalent)
- •Coagulation disorders (INR >1.5 or APTT >1.5×ULN) or ongoing anticoagulation therapy
- •Poor vascular access precluding serial venipuncture (>5 mL per draw)
- •Active hepatitis B (HBV DNA >2000 IU/mL), hepatitis C, or HIV infection
- •Uncontrolled bacterial or fungal infection requiring systemic treatment
- •Pregnancy or lactation
- •Severe psychiatric disorder or communication barriers affecting informed consent or follow-up compliance
- •Withdrawal Criteria:
- •Participant voluntary withdrawal with signed withdrawal statement
- •Major protocol violations: failure to receive ≥2 cycles of planned chemoimmunotherapy; missing ≥2 critical timepoint blood samples (baseline, cycle 2)
- •Uncontrollable grade ≥3 immune-related adverse events requiring permanent discontinuation of PD-1 inhibitor
- •Study Termination Criteria:
- •Disease progression confirmed by imaging per RECIST 1.1 or clinical progression requiring radiotherapy
- •Death or loss to follow-up >6 months
- •Unacceptable grade 4 treatment-related toxicity
- •Investigator determination that continued participation poses health risk to patient
- •Study terminated by ethics committee for scientific or administrative reasons
研究组 & 干预措施
NSCLC Patients Receiving Chemoimmunotherapy
Patients with stage IIIB-IV non-small cell lung cancer receiving standard PD-1 inhibitor (such as pembrolizumab) combined with platinum-based chemotherapy (such as pemetrexed/carboplatin or paclitaxel/carboplatin regimen). Peripheral blood samples collected at baseline and after cycle 2 for ETAST quantification using CTT-NanoDT technology.
干预措施: Circulating Tumor-Specific T Cell Nanodetection Technology (CTT-NanoDT) (Diagnostic Test)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: From treatment initiation to first documented disease progression or death, assessed up to 24 months
Time from first dose of chemoimmunotherapy to first documented disease progression per RECIST 1.1 criteria (assessed by independent radiology committee) or death from any cause, whichever occurs first. Tumor assessments performed every 2 treatment cycles (approximately every 6 weeks).
次要结局
- Change in Effector Tumor Antigen-Specific T Cells (ΔETASTs)(From baseline to after completion of cycle 2 (approximately day 42))
- Predictive Performance Comparison: ΔETASTs vs. Traditional Biomarkers(At 6 months and 12 months after treatment initiation)
- Objective Response Rate (ORR)(Best overall response from treatment initiation through study completion, up to 24 months)
- Overall Survival (OS)(From treatment initiation to death from any cause, assessed up to 24 months)
- Incidence of Treatment-Related Adverse Events(From treatment initiation through 30 days after last treatment dose, up to approximately 24 months)
研究者
Weibiao Zeng
Attending Physician
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine