Neoadjuvant Chemotherapy Combined With Bispecific Antibody Versus Monoclonal Antibody in Locally Advanced Non-Small Cell Lung Cancer: A Multicenter, Randomized Controlled Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Pathologic complete response (PCR) rate
研究概览
简要总结
Surgical intervention remains the primary treatment option for early-stage lung cancer. With the proven efficacy of immunotherapy in the treatment of advanced non-small cell lung cancer (NSCLC), neoadjuvant immunotherapy has increasingly become a focal point of research. Blocking vascular endothelial growth factor (VEGF) not only inhibits the proliferation of vascular endothelial cells and the formation of new blood vessels but also improves the tumor microenvironment and enhances the infiltration of cytotoxic T lymphocytes within it. Simultaneously targeting the VEGF and PD-L1 pathways can create a synergistic anti-cancer effect. PM8002 injection is a bispecific antibody drug that targets both PD-L1 and VEGF, functioning as a dual-action agent that combines immune suppression and anti-angiogenesis. In patients with locally advanced stage II-III NSCLC, neoadjuvant therapy that concurrently targets PD-L1/VEGF in combination with chemotherapy can improve pathological response rates, provided that the safety of the drug combination is maintained. This approach offers additional benefits to patients, prolongs event-free survival (EFS), and improves prognosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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
- •The patient shall sign the Informed Consent Form.
- •Aged 18 ≥ years.
- •Histological or cytological diagnosis of NSCLC by needle biopsy, and stage II-III confirmed by imageological examinations (CT, PET-CT or EBUS)，and have not previously received anti-tumor treatment.
- •Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or
- •Life expectancy is at least 12 weeks.
- •At least 1 measurable lesion according to RECIST 1.
- •Patients with good function of other main organs (liver, kidney, blood system, etc.)
- •Patients with lung function can tolerate surgery;
- •Without systematic metastasis (including M1a, M1b and M1c);
- •Fertile female patients must voluntarily use effective contraceptives not less than 120 days after chemotherapy or the last dose of toripalimab (whichever is later) during the study period, and urine or serum pregnancy test results within 7 days prior to enrollment are negative.
- •Unsterilized male patients must voluntarily use effective contraception during the study period not less than 120 days after chemotherapy or the last dose of toripalimab (whichever is later).
排除标准
- •Patients with lung adenocarcinoma with confirmed EGFR mutations or ALK rearrangements;
- •Histological evidence of small cell components;
- •Patients with other malignant tumors within five years prior to the start of this trial;
- •Having received any systemic anti-cancer treatment for NSCLC, including surgical treatment, local radiotherapy, cytotoxic drug treatment, targeted drug treatment, and experimental treatment, etc.;
- •Concomitant unstable systemic diseases, including active infections, uncontrolled hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg), unstable angina, angina that started within the last 3 months, congestive heart failure (≥New York Heart Association [NYHA] Class II), myocardial infarction (within 6 months prior to enrollment), severe arrhythmias requiring drug treatment, liver, kidney, or metabolic diseases;
- •Active, known, or suspected autoimmune diseases, or autoimmune paraneoplastic syndromes requiring systemic treatment;
- •Allergy to the trial drug;
- •Currently diagnosed with interstitial lung disease;
- •Concomitant HIV infection or active hepatitis;
- •Pregnant or lactating women;
- •Patients with neurological or psychiatric disorders who are unable to cooperate;
- •Concurrently participating in another therapeutic clinical study;
- •Other situations deemed unsuitable for enrollment by the investigator.
研究组 & 干预措施
Exploratory arm
In this arm, 20 patients with locally advanced Non-small cell lung cancer will receive 4 circles of neoadjuvant PM8002 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
干预措施: Carboplatin (Drug)
Exploratory arm
In this arm, 20 patients with locally advanced Non-small cell lung cancer will receive 4 circles of neoadjuvant PM8002 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
干预措施: PM8002 (Drug)
Exploratory arm
In this arm, 20 patients with locally advanced Non-small cell lung cancer will receive 4 circles of neoadjuvant PM8002 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
干预措施: Nab-paclitaxel (Drug)
Exploratory arm
In this arm, 20 patients with locally advanced Non-small cell lung cancer will receive 4 circles of neoadjuvant PM8002 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
干预措施: Surgery (Procedure)
PM8002 arm
Patients with locally advanced Non-small cell lung cancer will be randomized into this arm (70 patients) and receive 4 circles of neoadjuvant PM8002 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
干预措施: PM8002 (Drug)
PM8002 arm
Patients with locally advanced Non-small cell lung cancer will be randomized into this arm (70 patients) and receive 4 circles of neoadjuvant PM8002 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
干预措施: Nab-paclitaxel (Drug)
PM8002 arm
Patients with locally advanced Non-small cell lung cancer will be randomized into this arm (70 patients) and receive 4 circles of neoadjuvant PM8002 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
干预措施: Carboplatin (Drug)
PM8002 arm
Patients with locally advanced Non-small cell lung cancer will be randomized into this arm (70 patients) and receive 4 circles of neoadjuvant PM8002 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
干预措施: Surgery (Procedure)
Sintilimab arm
Patients with locally advanced Non-small cell lung cancer will be randomized into this arm (70 patients) and receive 4 circles of neoadjuvant Sintilimab combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
干预措施: Sintilimab (Drug)
Sintilimab arm
Patients with locally advanced Non-small cell lung cancer will be randomized into this arm (70 patients) and receive 4 circles of neoadjuvant Sintilimab combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
干预措施: Nab-paclitaxel (Drug)
Sintilimab arm
Patients with locally advanced Non-small cell lung cancer will be randomized into this arm (70 patients) and receive 4 circles of neoadjuvant Sintilimab combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
干预措施: Carboplatin (Drug)
Sintilimab arm
Patients with locally advanced Non-small cell lung cancer will be randomized into this arm (70 patients) and receive 4 circles of neoadjuvant Sintilimab combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
干预措施: Surgery (Procedure)
结局指标
主要结局
Pathologic complete response (PCR) rate
时间窗: Up to 30 months
PCR rate is defined as the proportion of participants who have achieved pathologic complete response (on routine hematoxylin and eosin staining, no tumor cell can be found in tumor bed or lymph node) in all participants.
次要结局
- Event-free survival (EFS)(Up to 60 months)
- Overall survival (OS)(Up to 60 months)
- Major pathologic response (MPR) rate(Up to 30 months)
- Objective response rate (ORR)(Up to 30 months)
- R0 resection rate(Up to 30 months)
- Treatment-related adverse event (TRAE)(Up to 30 months)
- Health related quality of life (HRQol) composite(Up to 5 months)
研究者
Peng Zhang
Professor
Shanghai Pulmonary Hospital, Shanghai, China