Clinical trial NCT04613804: Toripalimab as Maintenance Therapy in Patients With Driver-gene Negative Advanced NSCLC After First-line Chemotherapy
Official title: Toripalimab as Maintenance Therapy in Patients With Driver-gene Negative Advanced NSCLC After First-line Chemotherapy ：a Single-arm Phase II Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: NSCLC Stage IV
Keywords: driver-gene negative advanced NSCLC
maintenance treatment
Lead sponsor: Fujian Cancer Hospital
Sponsor class: OTHER_GOV
First posted: 2020-11-03
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This study is a single-center, single-arm Phase II study. Qualified subjects will be treated with toripalimab every three weeks as a treatment cycle. After every two cycles, they will be evaluated the efficacy of tumor treatment by imaging and the safety of treatment.
Primary purpose: TREATMENT

Brief summary: Lung cancer is the malignant tumor with the highest incidence and mortality in China. Non-small cell lung cancer (NSCLC) ,which includes non-squamous cell carcinoma (including adenocarcinoma, large cell carcinoma, and other cell types) and squamous cell carcinoma, accounts for about 80% of lung cancer. Platinum-based two-drug chemotherapy is the first-line standard treatment for driver-gene negative advanced NSCLC, but most patients experience disease progression after 4 to 6 months. To extend the efficacy of first-line treatment, maintenance therapy is a logical clinical option for patients who are effective after 4 to 6 cycles of standard treatment. There is currently no standard regimen for maintenance treatment of NSCLC. We evaluated the effectiveness and safety of maintenance therapy with the anti-PD-1 monoclonal antibody (Toripalimab injection) followed by the first-line standard regimen in advanced NSCLC patients who are effective after standard treatment. With a view to exploring treatment methods that are effective for the maintenance treatment of driver-gene negative advanced NSCLC and have little toxic and side effects,thereby improving the survival prognosis of these patients.

Detailed description: Platinum-based two-drug chemotherapy is the first-line standard treatment for driver-negative advanced NSCLC, but most patients experience disease progression after 4 to 6 months. To extend the efficacy of first-line treatment, maintenance therapy is a logical clinical option for patients who are effective after 4 to 6 cycles of standard treatment. There is currently no standard regimen for maintenance treatment of NSCLC. We evaluated the effectiveness and safety of the anti-PD-1 monoclonal antibody (Toripalimab injection) followed by maintenance therapy in advanced NSCLC that was effective in the first-line standard regimen.Thereby improving the survival prognosis of advanced NSCLC.

Eligibility criteria: Criteria:

Inclusion Criteria:

* Fully understand the research and voluntarily sign the informed consent form (ICF)
* Age 18 to 75 years
* Histological or cytological documentation of non-small cell lung cance.
* Diagnosed as stage IV by imaging (staging according to AJCC eighth edition).
* Gene test is negative for EGFR, ALK, ROS1 confirmed by molecular pathology (tissue, ARMS method or NGS).
* Previously received first-line standard chemotherapy for non-small cell lung cancer (platinum combined with third-generation chemotherapy drugs in a two-drug combination regimen: pemetrexed or paclitaxel or docetaxel or gemcitabine or vinorelbine combined with cisplatin or carboplatin), and which were assessed the effectiveness by imaging(SD, PR or CR).
* At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria measured within 4 weeks prior to registration.
* ECOG performance status 0-1
* Expected overall survival time≥3 months
* Adequate bone marrow, Coagulation function，hepatic and renal function should be assessed by the following laboratory requirements conducted within 7 days before starting study treatment:

  * Leukocytes ≥ 3.0 x109/ L, absolute neutrophil count (ANC) ≥ 1.5 x109/ L, platelet count ≥ 100 x109/ L, hemoglobin (Hb) ≥9g/ dL.
  * Total bilirubin ≤ 1.5 x the upper limit of normal (ULN).
  * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN.
  * Serum creatinine ≤ 1.5 x the ULN.
  * Calculated creatinine clearance or 24 hour creatinine clearance ≥ 40 mL/ min.
  * INR≤1.5, Activated partial thromboplastin time(APTT)≤1.5×ULN.
* Patients with hepatitis B virus (HBV) infection and inactive/asymptomatic HBV carriers, or patients with chronic or active HBV, if the HBV DNA is \<500IU/ml, or 2500copies/ml at the time of screening,can enter the group.
* Male subjects and women of childbearing age must have contraception within 24 weeks from the start of the study to the last time of using the drug.

Exclusion Criteria:

* Tumor histology or cytology pathology confirmed with small cell lung cancer components or sarcomatoid lesions.
* Previously received any T-cell co-stimulation or immune checkpoint therapy, including but not limited to CTLA-4 inhibitors, PD-1 inhibitors, PD-L1 / 2 inhibitors or other drugs that target T cells.
* Major autoimmune diseases.
* Subjects who were vaccinated or planned to be vaccinated within 4 weeks before the first time using the study drug.
* LD, drug-induced pneumonia, radiation pneumonitis requiring steroid therapy, or clinically active pneumonia or severe pulmonary dysfunction.
* TB or subjects with a history of active tuberculosis infection ≤ 48 weeks before screening, whether or not treated.
* Symptomatic cardiac disease, such as: heart failure above NYHA level 2, unstable angina pectoris, myocardial infarction occurred within 24 weeks, clinically significant supraventricular or ventricular arrhythmias require treatment or intervention.
* Acquired immunosuppression (AIDS or major immunosuppressive agents)
* Suffering from active viral hepatitis. Defined as: Hepatitis B virus (HBV) infection and HBV DNA ≥ 2500 copies / ml; or Hepatitis C virus (HCV) infection (quantitative test results of anti-HCV positive and HCV RNA are greater than the lower limit of detection) .
* Mental illness, alcohol, drug or substance abuse
* Pregnant or lactating women.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: up to 12 months
Secondary outcomes:
measure: Overall survival time
timeFrame: Up to 36 months
measure: Objective response rate
timeFrame: up to 12 months
measure: Disease control rate
timeFrame: up to 12 months
measure: Adverse events rate
timeFrame: up to 12 months
Other outcomes:
measure: Changes in immune environment
timeFrame: up to 12 months
Locations:
city: Fuzhou
country: China
facility: Fujian cancer hospital
state: Fujian
Study officials:
affiliation: Fujian Cancer Hospital
name: Zhiyong He, master
role: STUDY_CHAIR
References: