T-Cell Repertoire Sequencing: Assessing Pembrolizumab Efficacy in Advanced Non-small Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 30
- 主要终点
- Objective Response Rate (ORR) per RECIST 1.1 - correlated to TCR repertoire data, such as clonality/diversity.
研究概览
简要总结
This is a single site, non-randomized trial for the assessment of intravenous (IV) pembrolizumab (also known as MK-3475) combined with pemetrexed/platinum-based chemotherapy in subjects with advanced or metastatic non-squamous non-small lung cancer (NSCLC) who have not previously received systemic therapy for advanced disease and in whom directed therapy is not indicated. Approximately 30 subjects will be enrolled in this trial to examine the clonality and diversity dynamics matched with disease response evaluated by RECIST 1.1.
详细描述
Subjects will receive pembrolizumab 200 mg combined with pemetrexed and platinum (investigator's choice of cisplatin or carboplatin), as indicated below:
Pembrolizumab 200 mg + pemetrexed 500 mg/m2 (with vitamin supplementation) + cisplatin 75 mg/m2 OR carboplatin AUC 5, all on Day 1 every 3 weeks (Q3W) for 4 cycles followed by pembrolizumab 200 mg + pemetrexed 500 mg/m2 Q3W until progression.
Treatment with pembrolizumab and pemetrexed will continue until 35 trial treatments have been administered, documented disease progression or unacceptable adverse event(s).
Patients will be stratified according to clinical and histopathological parameters: 1. PD-L1 status (PD-L1 >/= 1 or <1) 2. Age < 65 vs => 65 3. Smoking history yes vs no 4. Platinum chemotherapy: cisplatin vs. carboplatin 5. Immune-related adverse events (irAEs).
TCR repertoire clonality and diversity will serve as an assessment measure for treatment response, along with PET/CT-scans, tumor exomal profile and ctDNA dynamics.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- •Have measurable disease based on RECIST 1.
- •Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- •Archival tumor tissue sample or newly obtained [core, incisional or excisional] biopsy of a tumor lesion not previously irradiated has been provided.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Adequate organ function.
排除标准
- •Pregnancy or breastfeeding
- •Aberration in a known targetable molecular driver.
- •Received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor.
- •Received prior systemic anti-cancer therapy for metastatic disease.
- •Received prior radiotherapy within 2 weeks of start of study intervention.
- •Major surgery within 14 days.
- •Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.
- •Known additional malignancy that is progressing or has required active treatment within the past 3 years.
- •Known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated or asymptomatic brain metastases may participate provided they are radiologically stable.
研究组 & 干预措施
Pembrolizumab + Carboplatin+ Pemetrexed
干预措施: Pembrolizumab 50 MG Injection [Keytruda] (Drug)
结局指标
主要结局
Objective Response Rate (ORR) per RECIST 1.1 - correlated to TCR repertoire data, such as clonality/diversity.
时间窗: 5 years
ORR defined as the percentage of participants who achieve a confirmed complete response (CR) or partial response (PR) per RECIST 1.1 as assessed by the investigator. By integrating serial TCR repertoire sequencing (Rep-seq) of NSCLC patients treated with pembrolizumab and platinum-based chemotherapy regimens we aim to capture the temporal clonality and diversity dynamics with the disease response.
次要结局
- Objective Response Rate (ORR) correlated with circulating tumor DNA (ctDNA), by measurement of variant allele frequency (VAF).(5 years)
研究者
Ari Raphael
Head Oncology Day-care unit
Tel Aviv Medical Center