A Single-arm Exploratory Clinical Study on the Efficacy and Safety of Toripalimab Combined With Bevacizumab, Nab-paclitaxel and Carboplatin for Untreated Metastatic Pulmonary Sarcomatoid Carcinoma
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Progress Free Survival(PFS)
研究概览
简要总结
This study aimed to evaluate the efficacy and safety of first-line Toripalimab combined with bevacizumab, nab-paclitaxel and carboplatin in the treatment of patients with advanced pulmonary sarcomatoid carcinoma.
详细描述
Pulmonary sarcomatoid carcinoma(PSC) is a rare primary lung cancer, which belongs to the category of non-small cell lung cancer(NSCLC), accounting for about 0.3%-1.3% of lung cancers .Platinum-based combination chemotherapy is the standard adjuvant chemotherapy and palliative chemotherapy for NSCLC, and it is also commonly used for PSC. Advanced PSC has a low response rate to systemic chemotherapy and a short duration of curative effect. The primary progression rate of aggressive platinum-based chemotherapy is 60%-70%, showing that PSC is highly resistant to multiple chemotherapeutics. In recent years, the progress of targeting MET tyrosine kinase mutations has been relatively rapid, but most of the mutant PSCs targeting EGFR, KRAS, ALK, and BRAF V600E are case reports and there is no effective treatments. Immunotherapy has rewritten the treatment pattern of NSCLC. However, the current application of immunotherapy in PSC are mostly case reports. In immunotherapy, IMpower150 research data suggests that the combination of immunity and anti-angiogenesis + platinum-containing dual-agent chemotherapy can bring sustained OS benefits in NSCLC patients , and safety tolerated. However, PSC has moderate to high tumor mutation burden (TMB >10 mutations/Mb). This high mutation rate may increase tumor immunogenicity, making immunotherapy a better treatment option. At the same time, VEGF, as a cytokine that promotes the growth and differentiation of vascular endothelial cells, plays a decisive role in promoting tumor neovascularization. In this regard, immunotherapy combined with anti-angiogenesis and chemotherapy is worth exploring in the treatment of PSC.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1.18 to 75 years old, no gender limit;
- •2.ECOG PS: 0～2 points;
- •3.Untreated patients with stage IV pulmonary sarcomatoid carcinoma are staged according to the AJCC eighth edition non-small cell lung cancer staging standard;
- •4.Pulmonary sarcomatoid carcinoma confirmed by histopathology has at least one measurable lesion according to RECIST standard 1.1, and the lesion has not received radiotherapy;
- •5.The functions of important organs meet the following requirements (no blood components and cell growth factors are allowed to be used 2 weeks before the start of the research treatment) : Absolute Neutrophil Count (ANC) ≥1.5×10 E+9/L, Hemoglobin (HB) ≥9g/dL, Platelets (PLT)≥90×10 E+9/L, Serum Albumin (ALB)≥2.8g/dL, Total Bilirubin (TBIL) ≤1.5 ULN, ALT、AST≤2.5 UILN(If abnormal liver function is caused by liver metastasis, ≤5 ULN), Serum creatinine sCr≤1.5 ULN, endogenous creatinine clearance ≥50ml/min (Cockcroft-Gault formula) ,Normal thyroid function;
- •6.Expected survival time ≥ 3 months;
- •7.Female subjects with fertility should undergo a urine or serum pregnancy test within 72 hours before receiving the first study drug administration, and prove to be negative, and are willing to use effective during the test period to 3 months after the last administration Methods of contraception. For male subjects whose partners are women of childbearing age, effective methods of contraception should be used during the trial and within 3 months after the last administration;
- •8.The patients joined the study voluntarily and signed an informed consent form (ICF). They had good compliance and cooperated with follow-up.
排除标准
- •1.Patients with pathological types and primary lesions that do not meet the inclusion criteria;
- •2.There is known evidence that patients have mutations in any of the genes above EGFR, ROS-1, ALK, and c-MET;
- •3.Suffer from any active autoimmune diseases, such as interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism (can be included after hormone replacement therapy is normal);
- •4.Known to be allergic to other monoclonal macromolecular protein preparations, or to any of the components of Toripalimab;
- •5.Have received other PD-1 monoclonal antibody therapy or other immunotherapy against PD-1/PD-L1;
- •6.Active infection or fever of unknown origin occurred during the screening period and before the first administration>38.5℃ (according to the judgment of the investigator, the subject can be included in the group for fever caused by the tumor);
- •7.Suffering from uncontrolled clinical symptoms or diseases of the heart, such as: (1) Heart failure above NYHA II; (2) Unstable angina pectoris; (3) Myocardial infarction occurred within 1 year; (4) Patients with clinically significant supraventricular or ventricular arrhythmia requiring clinical intervention.
- •8.Suffering from high blood pressure and cannot be well controlled by antihypertensive drugs (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg);
- •9.Abnormal coagulation function (INR>2.0, PT>16s), have bleeding tendency or are receiving thrombolytic therapy, and allow preventive use of low-dose aspirin and low-molecular-weight heparin;
- •10.Obvious coughing up blood or hemoptysis of 10ml or more per day in the 2 months before enrollment;
- •11.Have significant clinically significant bleeding symptoms or have a clear bleeding tendency within 3 months before enrollment;
- •12.Suffer from congenital or acquired immune function defects (such as HIV infection);
- •13.Received anti-tumor monoclonal antibody (mAb) within 4 weeks before the first use of the study drug, or the adverse event caused by the previously received drug has not recovered (ie ≤ grade 1 or reached the baseline level). Note: Except for subjects with ≤ Grade 2 neuropathy or ≤ Grade 2 hair loss, if the subject has undergone major surgery, the toxic reaction and/or complications caused by the surgical intervention must be fully recovered before starting treatment;
- •14.Live vaccines have been vaccinated within 4 weeks before the first use of the study drug. Inactivated virus vaccines for seasonal influenza and injection are allowed, but live attenuated influenza vaccines for nasal use are not allowed;
- •15.According to the judgment of the investigator, the subject has other factors that may cause him to be forced to terminate the study halfway, such as suffering from other serious diseases (including mental illness) requiring combined treatment, severely abnormal laboratory test values, family or social factors, It may affect the safety of subjects or the collection of experimental data;
- •16.The investigator judged other situations not suitable for inclusion in this study.
研究组 & 干预措施
Toripalimab Combined With Bevacizumab, Nab-paclitaxel and Carboplatin
Drugs: Toripalimab, 240mg (6ml)/bottle, ivgtt, d1, q3w, administration until PD or death, the longest use time is two years.
Drugs: Bevacizumab, 7.5mg/kg, ivgtt, d1, q3w,the longest use time is two years.
Drugs: Nab-paclitaxel, 260mg/m2,ivgtt,d1 or 130mg/m2,ivgtt,d1,8, q3w, up to six cycles.
Drugs: Carboplatin, AUC=4～5, ivgtt, d1, q3w, up to six cycles.
干预措施: Toripalimab (Drug)
Toripalimab Combined With Bevacizumab, Nab-paclitaxel and Carboplatin
Drugs: Toripalimab, 240mg (6ml)/bottle, ivgtt, d1, q3w, administration until PD or death, the longest use time is two years.
Drugs: Bevacizumab, 7.5mg/kg, ivgtt, d1, q3w,the longest use time is two years.
Drugs: Nab-paclitaxel, 260mg/m2,ivgtt,d1 or 130mg/m2,ivgtt,d1,8, q3w, up to six cycles.
Drugs: Carboplatin, AUC=4～5, ivgtt, d1, q3w, up to six cycles.
干预措施: Bevacizumab (Drug)
Toripalimab Combined With Bevacizumab, Nab-paclitaxel and Carboplatin
Drugs: Toripalimab, 240mg (6ml)/bottle, ivgtt, d1, q3w, administration until PD or death, the longest use time is two years.
Drugs: Bevacizumab, 7.5mg/kg, ivgtt, d1, q3w,the longest use time is two years.
Drugs: Nab-paclitaxel, 260mg/m2,ivgtt,d1 or 130mg/m2,ivgtt,d1,8, q3w, up to six cycles.
Drugs: Carboplatin, AUC=4～5, ivgtt, d1, q3w, up to six cycles.
干预措施: Nab-paclitaxel (Drug)
Toripalimab Combined With Bevacizumab, Nab-paclitaxel and Carboplatin
Drugs: Toripalimab, 240mg (6ml)/bottle, ivgtt, d1, q3w, administration until PD or death, the longest use time is two years.
Drugs: Bevacizumab, 7.5mg/kg, ivgtt, d1, q3w,the longest use time is two years.
Drugs: Nab-paclitaxel, 260mg/m2,ivgtt,d1 or 130mg/m2,ivgtt,d1,8, q3w, up to six cycles.
Drugs: Carboplatin, AUC=4～5, ivgtt, d1, q3w, up to six cycles.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Progress Free Survival(PFS)
时间窗: up to 2 years
It is defined as the time interval from randomization of patients to disease progression or death, whichever comes first. There was no progress or the time of disease progression was not recorded when the trial was withdrawn, and the date of the last examination was used as the end date.
次要结局
- Disease Control Rate(DCR)(up to 2 years)
- Overall response rate(ORR)(up to 2 years)
- Overall Survival(OS)(up to 2 years)
- Incidence of AEs(up to 2 years)
- the quality of life (QoL)(up to 2 years)
研究者
Juan LI, MD
MD
Sichuan Cancer Hospital and Research Institute