A Prospective, Single-arm, Multicenter, Phase II Clinical Study on Envafolimab Combined With Disitamab Vedotin And Carboplatin for Resectable, Stage II-III, HER2-Mutant Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- MPR rate
研究概览
简要总结
This is a prospective, single-arm, multi-center, phase II clinical study to evaluate the efficacy and safety of Envafolimab injection (PD-L1) combined with Disitamab Vedotin (HER2 ADC) and Carboplatin for resectable, HER2-Mutant, stage II-IIIB, NSCLC.
详细描述
The eligible patients will receive 4 cycles of subcutaneous Envafolimab injections (300mg, d1, Q3W) in combination with intravenous Disitamab Vedotin (2.5mg/kg, d1, Q3W) and carboplatin (AUC5, d1, Q3W), followed by surgical resection 4-6 weeks after the last dose of neoadjuvant therapy. The tumor tissue samples collected from subjects during the study will be submitted to the authorized central laboratory for evaluation of pathological response and translational research. Dynamic blood samples will be collected at baseline, after neoadjuvant treatment and after surgery for tumor-informed minimal residual disease (MRD) testing. After surgery, patients will be provided with or without adjuvant therapy according to MRD results. Patients with postoperative positive MRD result will be provided with adjuvant treatment after multidisciplinary discussion. The primary endpoint of this study is major pathologic response (MPR) rate. All the subjects will be followed up for overall survival, until death, withdrawal of informed consent or end of study.
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
盲法说明
No Masking
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
- •Having sufficient understanding of this study and being willing to sign the informed consent form (ICF);
- •Aged 18-75 years, male or female;
- •Treatment-naive, histologically confirmed resectable, stage II, IIIA, IIIB (AJCC staging system, version 9) NSCLC; cTNM stage can be confirmed through PET-CT or pathological biopsy; N2 should be confirmed by mediastinoscopy or EBUS.
- •PET-CT or CT plus MRI should be completed before enrollment;
- •HER2 mutations identified by histological specimens;
- •Measurable lesions based on the response evaluation criteria in solid tumors version 1.1 (RECIST v1.1);
- •Tumor tissue specimens and blood sample available for detection of MRD and biomarkers (the tumor tissue specimens must be freshly obtained or archived samples within 3 months prior to enrollment);
- •ECOG score 0-1;
- •No contraindications to immunotherapy;
- •Adequate organ function:
- •Being willing and able to comply with the visits, treatment plan, laboratory examinations and other study procedures scheduled in the study;
- •Pulmonary function being able to withstand the planned surgery evaluated by surgeons;
- •Women of childbearing potential must undergo a serum pregnancy test within 3 days prior to the first dose and the result must be negative. Female patients of childbearing potential and male subjects whose partners are women of childbearing potential must agree to use highly effective contraceptive methods during the study period and within 180 days after the last dose of study drug
排除标准
- •Presence of locally advanced, unresectable or metastatic disease; unresectable includes the unresectable defined in the Chinese expert consensus on the multidisciplinary diagnosis and treatment for stage III non-small cell lung cancer (2019), including partial stage IIIA and IIIB and all the stage IIIC;
- •Participants with known EGFR sensitive mutations or ALK translocation, KRAS sensitive mutations, BRAF V600E, ROS1 fusions, RET fusions, MET exon 14 alterations and MET amplification, NTRK fusions;
- •Previous treatment with systemic antitumor therapy for early NSCLC, including investigational product;
- •History of (non-infectious) pneumonitis/interstitial lung disease requiring steroid treatment, or ongoing pneumonitis/interstitial lung disease requiring steroid treatment;
- •Active tuberculosis;
- •Active infection requiring systemic treatment;
- •Subjects with any known or suspected autoimmune disorder or immunodeficiency, with the following exceptions: hypothyroidism, hormone therapy is not needed, or well controlled at physiological dose; controlled type I diabetes;
- •Uncontrolled active hepatitis B (defined as positive hepatitis B surface antigen [HBsAg] in screening period with HBV-DNA detected higher than the upper limit of normal at the clinical laboratory of the study center); (the subjects with HBV-DNA assay <500 IU/mL within 28 days prior to randomization who have received local standard antiviral therapy for at least 14 days and are willing to receive antiviral therapy continuously during the study can be enrolled); active hepatitis C (defined as positive hepatitis C surface antibody [HCsAb] in screening period and positive HCV-RNA);
- •Known human immunodeficiency virus (HIV) infection (known positive HIV antibody);
- •Vaccination of live vaccine within 30 days prior to the first dose. Including but not limited to the following: parotitis, rubella, measles, varicella/ herpes zoster (varicella), yellow fever, Rabies, Bacille Calmette-Guérin (BCG) and typhoid vaccine (inactivated virus vaccine allowed);
- •Previous use of PD-1/PD-L1 agent or the drug acting on another targeted T cell receptor (e.g., CTLA-4, OX-40);
- •Severe allergic reaction to other monoclonal antibodies;
- •Known serious or uncontrolled pre-existing diseases; including but not limited to cardiovascular events with hemodynamic instability, symptomatic cerebrovascular events, and hepatic cirrhosis above Child-Pugh A within 6 months;
- •Other malignant tumors within 5 years prior to the first dose, except non-small cell lung cancer. The malignant tumors with negligible risk of metastasis or death (e.g., expected disease-free survival > 5 years) and expected to achieve radical outcomes after treatment (e.g., sufficiently treated carcinoma in situ of cervix, basal or squamous cell skin cancer, ductal carcinoma in situ treated for radical surgery) can be excluded
研究组 & 干预措施
Intervention/Treatment
Patients were treated with subcutaneous Envafolimab injections (300mg, d1, Q3W) combined with intravenous Disitamab Vedotin (2.5mg/kg, d1, Q3W) and carboplatin (AUC5, d1, Q3W)
Participants receive totally 4 cycles of Envafolimab combined with Disitamab Vedotin and carboplatin during perioperative period
干预措施: Envafolimab injections+intravenous Disitamab Vedotin+carboplatin (Drug)
结局指标
主要结局
MPR rate
时间窗: up to 7 weeks after neoadjuvant
Major Pathological Response (MPR) Rate is defined as the percentage of participants having ≤10% viable tumor cells in the resected primary tumor and all resected lymph nodes in neoadjuvant therapy.
次要结局
- pCR rate(pCR:up to 7 weeks after neoadjuvant;)
- ORR(ORR:up to 7 weeks after neoadjuvant;)
- EFS(EFS up to 3 years)
- OS(OS up to 3 years)
- Safety evaluation of subjects(Safety: 90 days after the last administration)
- Molecular progression of ctDNA based on MRD monitoring(up to 3 years)