A Multicenter Clinical Study Evaluating the Efficacy and Safety of Sacituzumab Tirumotecan Combined With Anlotinib as Second-Line Treatment for Patients With Driver Gene-Negative Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR) Assessed by Investigator per RECIST v1.1
研究概览
简要总结
The goal of this clinical trial is to evaluate whether sacituzumab govitecan (TROP2 antibody-drug conjugate) in combination with anlotinib (multi-target tyrosine kinase inhibitor) can improve treatment efficacy and safety in patients with driver gene-negative locally advanced or metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) after failure of first-line immunotherapy combined with platinum-based chemotherapy.
The main questions it aims to answer are:
Can the combination of sacituzumab govitecan and anlotinib improve progression-free survival (PFS) compared to historical second-line chemotherapy outcomes? What is the objective response rate (ORR) and safety profile of this combination therapy in this patient population? Can baseline multi-omics biomarkers (metabolomics, proteomics, and ctDNA genomics) predict response or resistance to sacituzumab govitecan?
If there is a comparison group:
This is an exploratory single-arm study, and outcomes will be compared with historical controls of second-line chemotherapy in similar patient populations.
Participants will:
Receive sacituzumab govitecan combined with anlotinib according to the study treatment schedule Undergo routine imaging evaluations to assess tumor response Provide peripheral blood samples before treatment for metabolomic, proteomic, and ctDNA genomic analyses Be monitored regularly for treatment response and adverse events
详细描述
- Scientific Rationale and Hypotheses This study investigates the synergistic efficacy and safety of combining Lukang-sacituzumab (SKB264/MK-2870), a third-generation TROP2-directed antibody-drug conjugate (ADC), with Anlotinib, a multi-targeted tyrosine kinase inhibitor (TKI).
Mechanism of Synergy: Preclinical data suggest that anti-angiogenic agents like Anlotinib can "normalize" the tumor vasculature. This process reduces tumor interstitial fluid pressure and improves blood perfusion, which is hypothesized to enhance the delivery and intra-tumoral penetration of large-molecule ADCs like Lukang-sacituzumab.
Target Population Strategy: For driver-gene-negative non-squamous non-small cell lung cancer (nsq-NSCLC) patients who have progressed after first-line immuno-chemotherapy, there is a critical need for chemotherapy-free or novel cytotoxic-enhanced regimens. TROP2 is an ideal target due to its widespread overexpression in this histological subtype. 2. Detailed Statistical Methodology (Simon's Two-Stage Optimal Design) The study utilizes a Simon's Two-Stage Optimal Design to minimize the number of subjects exposed to an potentially ineffective treatment (Type I error rate $\alpha$ = 0.05, Power $1-\beta$ = 0.80).
Stage 1 (Futility Assessment): Initially, 9 evaluable subjects will be enrolled. If 1 or 0 subjects achieve an objective response (CR or PR), the trial will be terminated early for lack of efficacy.
Stage 2 (Expansion): If 2 or more objective responses are observed in the first 9 subjects, enrollment will continue until a total of 38 evaluable subjects is reached.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 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
- •Age ≥18 years, regardless of gender.
- •Histologically or cytologically confirmed locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) non-squamous NSCLC, progressing after prior anti-PD-1/L1 monoclonal antibody combined with platinum-based doublet chemotherapy.
- •No known driver gene alterations such as EGFR, ALK, ROS1, NTRK, BRAF, MET, KRAS, HER2, RET, etc.
- •At least one measurable target lesion not previously irradiated, assessed by the investigator per RECIST v1.
- •ECOG performance status score of 0 or
- •Asymptomatic or locally treated and stable brain metastases are allowed.
- •Life expectancy ≥ 12 weeks.
- •Adequate organ and bone marrow function.
- •Agreement to use effective medical contraception from signing informed consent until 6 months after the last dose.
- •Voluntary participation, signed informed consent, and ability to comply with the protocol.
排除标准
- •Tumors histologically or cytologically confirmed with mixed small cell lung cancer, squamous cell carcinoma, neuroendocrine carcinoma, or carcinosarcoma components.
- •Prior treatment with TROP2-targeted therapy or any drug targeting topoisomerase I (including ADCs).
- •Known meningeal, brainstem, spinal cord metastases and/or compression, or active central nervous system (CNS) metastases.
- •Other malignancies within 3 years prior to dosing (except locally cured tumors like basal cell carcinoma, squamous cell carcinoma of the skin, cervical carcinoma in situ, etc.).
- •Presence of major cardiovascular diseases or risk factors within 6 months prior to dosing (e.g., myocardial infarction, severe arrhythmias, active myocarditis, major vascular disease requiring surgery).
- •Poorly controlled hypertension (systolic > 160 mmHg and/or diastolic > 100 mmHg).
- •History of (non-infectious) interstitial lung disease (ILD) or non-infectious pneumonitis requiring steroid treatment, or current active/suspected ILD/pneumonitis.
- •Documented severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or corneal disease preventing/delaying healing.
- •Active chronic inflammatory bowel disease, gastrointestinal obstruction, severe ulcer, gastrointestinal perforation, abdominal abscess, or acute gastrointestinal bleeding.
- •Risk of esophageal-tracheal or esophageal-pleural fistula.
- •Tumors invading major blood vessels or high risk of fatal bleeding.
- •Bleeding symptoms or any ≥CTCAE grade 3 bleeding event with unhealed wounds, ulcers, or fractures within 1 month prior to first dose.
- •Known active tuberculosis.
- •History of allogeneic organ transplant or allogeneic hematopoietic stem cell transplant.
- •HIV positive, history of AIDS, or active syphilis infection.
- •Major surgery within 4 weeks prior to dosing or planned major surgery during the study.
- •Current use of strong CYP3A4 inducers (must be avoided at least 3 weeks prior).
- •Live vaccine within 30 days prior to dosing or planned during the study.
- •Pregnant or lactating women.
- •Any condition that, in the investigator's opinion, interferes with the evaluation of the study drug or compromises subject safety.
研究组 & 干预措施
Sacituzumab Tirumotecan + Anlotinib
Patients in this arm receive Sacituzumab Tirumotecan administered via intravenous (IV) infusion at a dose of 4 mg/kg on Day 1 of each 14-day cycle (Q2W). Patients concurrently receive Anlotinib administered orally (PO) at a dose of 10 mg once daily before breakfast on Days 1 through 14 of each 21-day cycle (Q3W). The combination treatment will continue until radiographic disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-specified discontinuation criteria are met.
干预措施: Sacituzumab tirumotecan (Drug)
Sacituzumab Tirumotecan + Anlotinib
Patients in this arm receive Sacituzumab Tirumotecan administered via intravenous (IV) infusion at a dose of 4 mg/kg on Day 1 of each 14-day cycle (Q2W). Patients concurrently receive Anlotinib administered orally (PO) at a dose of 10 mg once daily before breakfast on Days 1 through 14 of each 21-day cycle (Q3W). The combination treatment will continue until radiographic disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-specified discontinuation criteria are met.
干预措施: Anlotinib (Drug)
结局指标
主要结局
Objective Response Rate (ORR) Assessed by Investigator per RECIST v1.1
时间窗: Up to 2 years (Assessed every 6 weeks for the first 48 weeks, then every 12 weeks thereafter until disease progression or death).
The objective response rate (ORR) is defined as the proportion of subjects with Complete Response (CR) or Partial Response (PR) out of the total subjects, assessed by the investigator according to RECIST v1.1.
次要结局
未报告次要终点