A Randomized, Controlled, Double-blind, Multicentre Phase III Clinical Study to Assess Efficacy and Safety of Envafolimab Plus Platinum-based Doublet Chemotherapy Versus Placebo Plus Platinum-based Doublet Chemotherapy as Neoadjuvant/Adjuvant Therapy in Subjects with Resectable Stage III Non-Small Cell Lung Cancer.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 180
- 试验地点
- 31
- 主要终点
- Major pathologic response (MPR) rate assessed by blinded independent pathology review (BIPR)
研究概览
简要总结
This is a Randomized, Controlled, Double-blind, Multicenter Phase III Clinical Study to Assess Efficacy and Safety of Envafolimab Plus Platinum-based Doublet Chemotherapy Versus Placebo Plus Platinum-based Doublet Chemotherapy as Neoadjuvant/Adjuvant Therapy in Subjects with Resectable Stage III Non-Small Cell Lung Cancer.
Eligible subjects who meet all inclusion criteria will be enrolled in the study and randomized to one of the two treatment groups: Experimental group or Control Group. The subjects in experimental group will receive Envafolimab along with platinum-based doublet chemotherapy while the control group subjects will receive placebo of Envafolimab along with platinum based doubled chemotherapy during the neoadjuvant period (3-4 cycles, each cycle is 3 weeks). Post-surgery in the adjuvant setting, the subjects in the experimental group will receive envafolimab injections, while those in the control arm will receive placebo of Envafolimab once every 3 weeks, up to 16 cycles. Post last dose, the subject will enter the follow-up phase which includes safety follow-up, tumor disease follow-up and survival follow-up. All randomized subjects will undergo survival follow-up until death, loss to follow-up, or withdrawal of informed consent, whichever occurs first.
The primary endpoint of the study is major pathologic response (MPR) rate assessed by blinded independent pathology review.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Volunteer to participate in the study and sign the informed consent form;
- •Age greater than or equal to 18 years old
- •Histological and/or cytological diagnosis of resectable Stage IIIA-IIIB(N2) NSCLC (IASLC Staging Handbook in Thoracic Oncology/American Joint Committee of Cancer[AJCC], 8th Edition).
- •Measurable lesion(s) based on the RECIST Version 1.1
- •ECOG performance status of 0 to 1
- •Expected survival greater than or equal to 6 months
- •The subject meets the criteria for radical surgery and the total lung function is able to withstand the proposed pneumonectomy procedure
- •Female subjects of childbearing potential must undergo a serum pregnancy test within 7 days prior to randomization, with a negative result, and male subjects with a partner of childbearing potential must agree to use a reliable and effective method of contraception during the study as per the study protocol.
排除标准
- •Tumour is confirmed as or combined with neuroendocrine carcinoma components (large cell carcinoma, small cell carcinoma, neuroendocrine carcinoma, etc.), or sarcomatous/sarcomatoid lesions, or adenosquamous carcinoma, or special pathological types (such as SMARCA4-deficient type, etc.)
- •Previous treatment with another target T cell receptors (e.g., CTLA-4, OX-40, etc.)
- •Subjects with known EGFR sensitive mutation or ALK translocation
- •Upper lung sulcus tumour or locally advanced unresectable or metastatic disease
- •Subjects who have previously received any anticancer treatment for the study disease (including chemotherapy, radiotherapy, immunotherapy, targeted therapy, etc.); or have received alternative traditional medicine (e.g., ayurveda, homeopathy, Chinese medicine) with anticancer indications within 2 weeks prior to randomization
- •Subjects diagnosed with any other malignancy within 5 years prior to randomization, except for cured localized cancers, including cervical carcinoma in situ, basal cell carcinoma, and low-grade prostate cancer, etc.
- •Subjects who have participated in other clinical studies within 4 weeks prior to randomization.
- •Subjects who have undergone major surgery (excluding diagnostic procedures) within 28 days prior to randomization, or who are expected to undergo non-study major surgery during the study
- •Subjects planned to receive cisplatin who have known or suspected hearing impairment, with consecutive hearing measurements greater than 25 dB.
- •Subjects with greater than or equal to Grade 2 peripheral neuropathy
- •Subjects with known or suspected interstitial pneumonia, radiation pneumonitis or other moderate/severe pulmonary diseases that may interfere with the detection or management of drug-related pulmonary toxicity and severely affect respiratory function
- •Any severe active infection, including active tuberculosis, and bacterial, fungal, or viral infections requiring systemic treatment within 14 days prior to randomization;
- •Active hepatitis B virus infection (HBsAg positive and/or HBcAb positive, with HBV-DNA quantification greater than or equal to 2000 IU/mL) or hepatitis C virus infection (HCV antibody positive and HCV-RNA quantification above the lower limit of detection)
- •Subjects with a known history of HIV infection
- •Subjects with uncontrolled or significant cardiovascular and cerebrovascular disease
- •Subjects who have had active autoimmune disease requiring systemic treatment within 2 years prior to randomization
- •Subjects who have used immunosuppressants or systemic hormone therapy for immunosuppressive purposes within 14 days prior to randomization (prednisone, greater than 10 mg/day or other equivalent hormone therapy)
- •Subjects who have received or are planned to receive a live attenuated vaccine within 28 days prior to randomization or during the study.
- •Subjects with a contraindication or history of hypersensitivity to any component of the study drug (including chemotherapy) or any known excipients
- •Pregnant or breastfeeding women
- •Subjects with other conditions that may interfere with participation in the study or are not expected to benefit from participation, or may affect the study results, such as a history of psychiatric disorders, drug addiction or substance abuse, or any other clinically significant disease or condition.
结局指标
主要结局
Major pathologic response (MPR) rate assessed by blinded independent pathology review (BIPR)
次要结局
- PK and Immunogenicity (Plasma-drug concentration of envafolimab)
- PK and Immunogenicity (ADA and Nab against envafolimab)
- Pathological complete response (pCR) rate assessed by BIPR
- Event Free Survival (FES)
- Disease-free survival (DFS)
- Overall survival (OS)
- Treatment emergent Adverse Events