The Efficacy and Safety of Chemotherapy and Immune Therapy Combined With Lactobacillus Johnsonii in Patients With Metastatic or Locally Advanced Unresectable or Recurrent EGFR/ALK Wild-type Adenocarcinoma Non-small Cell Lung Cancer (NSCLC), PD-L1 Positive (CPS≥1) Triple-negative Breast Cancer (TNBC) and HER2-negative Gastric or Gastro-oesophageal Junction Adenocarcinoma: a Multicenter, Randomized, Double-blind, Clinical Trial.
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 156
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
This study plans to enroll 156 patients aged 18-75, who will be randomly divided into two groups to evaluate the clinical efficacy and safety of chemotherapy and immune therapy combined with Lactobacillus johnsonii in patients with various advanced unresectable tumors.
This study was divided into three subgroups, with 48,52 and 56 subjects in each group respectively，randomly assigned to the experimental or control group in a 1:1 ratio.
Subgroup A will include 48 patients with histologically or cytologically confirmed metastatic or locally advanced unresectable or recurrent EGFR/ALK wild-type adenocarcinoma non-small cell lung cancer (NSCLC). The treatment regimen consists of chemotherapy combined with immunotherapy tislelizumab (200 mg IV on Day 1) + pemetrexed (500 mg/m² BSA IV on Day 1) + cisplatin (75 mg/m² BSA IV on Day 1). The experimental group will additionally receive oral Lactobacillus johnsonii (1×10¹¹ CFU, twice daily), while the control group will receive a placebo orally twice daily. Standard tumor treatment will be administered every 3 weeks, with follow-up every 6 weeks to assess treatment efficacy and drug-related adverse reactions. Follow-up time points: 0, 6, 12, 18, and 24 weeks.
Subgroup B will include 52 patients with histologically or cytologically confirmed metastatic or locally advanced unresectable or recurrent PD-L1-positive (CPS ≥1) triple-negative breast cancer (TNBC). The treatment regimen consists of toripalimab (240 mg IV on Day 1) + nab-paclitaxel (260 mg/m² BSA IV on Day 1) + carboplatin (300 mg/m² BSA IV on Day 1). The experimental group will additionally receive oral Lactobacillus johnsonii (1×10¹¹ CFU, twice daily), while the control group will receive a placebo orally twice daily. Standard tumor treatment will be administered every 3 weeks, with follow-up every 6 weeks to assess treatment efficacy and drug-related adverse reactions. Follow-up time points: 0, 6, 12, 18, and 24 weeks.
Subgroup C will include 56 patients with metastatic or locally advanced unresectable or recurrent HER2-negative gastric or gastroesophageal junction adenocarcinoma. The treatment regimen consists of tislelizumab (200 mg IV on Day 1) + oxaliplatin (130 mg/m² BSA IV on Day 1) + capecitabine (1000 mg/m² BSA orally twice daily, taken 30 minutes after meals on Days 1-14). The experimental group will additionally receive oral Lactobacillus johnsonii (1×10¹¹ CFU, twice daily), while the control group will receive a placebo orally twice daily. Standard tumor treatment will be administered every 3 weeks, with follow-up every 6 weeks to assess treatment efficacy and drug-related adverse reactions. Follow-up time points: 0, 6, 12, 18, and 24 weeks.
Primary Efficacy Endpoint: Progression-Free Survival (PFS): Time from randomization to tumor progression or death from any cause (whichever occurs first).
Secondary Efficacy Endpoints:
- Changes in gut microbiome composition in stool samples: qPCR and 16sRNA analysis of microbial composition, including Lactobacillus johnsonii, immunotherapy-related bacterial abundance, and microbial diversity.
- Changes in immune cell subsets in blood, just like Tregs, MDSCs, CD8+ T cells.
- Changes in blood levels of IL-6, IL-8, and other cytokines/chemokines.
- Changes in blood indole derivatives, for example, indolepropionic acid.
- Characterization of the tumor microenvironment in archived tumor samples.
- Objective Response Rate (ORR): Proportion of patients with tumor shrinkage meeting predefined criteria and sustained for a minimum duration (CR + PR).
- Disease Control Rate (DCR): Percentage of evaluable cases achieving response (PR+CR) or stable disease (SD).
- Duration of Response (DOR): Time from first objective response to disease progression (PD) or death before PD, reflecting the durability of ORR.
- Disease Control Rate (DCR): Percentage of evaluable cases achieving response (PR+CR) or stable disease (SD).
- Overall Survival (OS): Time from randomization to death from any cause.
- Percentage of patients with immune checkpoint inhibitor-related adverse events (irAEs).
详细描述
Research Objective This study is a randomized, double-blind, controlled, prospective multicenter clinical trial, designed to evaluate the clinical efficacy and safety of chemotherapy and immune therapy combined with Lactobacillus johnsonii in patients with various advanced unresectable solid tumors.
Study Methods:
Design: Randomized, controlled, double-blind, multicenter clinical study. Duration: 6-12 months. Start Date: Upon ethical approval and completion of clinical trial registration.
Study Design:
- Overall Design:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
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
- 否
入选标准
- •Signed informed consent.
- •Age 18-75 years.
- •Histologically confirmed unresectable/metastatic tumors:
- •EGFR/ALK wild-type adenocarcinoma non-small cell lung cancer (NSCLC) PD-L1+ (CPS≥1) triple-negative breast cancer (TNBC) HER2- gastric/gastroesophageal adenocarcinoma
- •≥1 measurable lesion (RECIST v1.1).
- •Progression after PD-1/PD-L1 inhibitor therapy (defined as:
- •≥2 doses administred.
- •Radiographic progression per RECIST/iRECIST/irRECIST, confirmed ≥4 weeks later.
- •Progression within 12 weeks of last PD-1/PD-L1 dose.
- •Adequate organ function.
- •ECOG performance status 0-
- •Negative pregnancy test (urine/serum β-HCG) for women of childbearing potential.
排除标准
- •1. Prior allogeneic transplantation (cells, tissues, or solid organs).
- •History of immune-related adverse events (irAEs) from immunomodulators (e.g., PD-1/PD-L1 or CTLA-4 inhibitors) leading to permanent discontinuation or Grade 3/4 severity.
- •3. Recent anticancer therapy (chemotherapy/immunotherapy/biologics/experimental drugs) within: <5 half-lives of the drug or <21 days before starting study treatment (whichever is shorter). Exceptions: Stable hormone therapy (e.g., for prostate/breast/ovarian cancer).
- •4. Concomitant corticosteroid use (>10 mg prednisone/day or equivalent) within 7 days prior to treatment, unless for physiological replacement (≤10 mg/day) or non-immunosuppressive purposes (e.g., inhaled/topical steroids).
- •5. Severe cardiac dysfunction, including: NYHA Class III-IV heart failure, symptomatic coronary artery disease, severe ventricular arrhythmias, myocardial infarction/unstable angina within 6 months.
- •6. Active autoimmune disease requiring systemic treatment (immunosuppressants/corticosteroids) in the past 2 years, except: Hormone replacement (thyroxine, insulin, physiologic corticosteroids).
- •7. Active severe infection requiring systemic therapy.
- •Antibiotic use completed within 2 weeks before the first dose.
- •Psychiatric or substance abuse disorders compromising protocol compliance.
- •Live vaccines administered within 28 days before treatment.
- •Active HIV or hepatitis (A/B/C) infection.
- •History of steroid-requiring (non-infectious) pneumonitis or current active pneumonitis.
- •13. Other malignancies requiring active treatment or progressing within 2 years (exceptions: Non-melanoma skin cancer, cervical/prostate carcinoma in situ).
- •14. Pregnancy or lactation.
- •Known intolerance/allergy to study drugs.
- •Other conditions deemed unsuitable by investigators.
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: From enrollment to the end of treatment at 24weeks
Progression-Free Survival (PFS): Time from randomization to tumor progression or death from any cause (whichever occurs first).
Progression-Free Survival (PFS)
时间窗: From enrollment to the end of treatment at 24weeks
Progression-Free Survival (PFS): Time from randomization to tumor progression or death from any cause (whichever occurs first).
次要结局
- Secondary Efficacy Endpoints(From enrollment to the end of treatment at 24 weeks)