A Randomized, Blind, Parallel Controlled, Multicenter Phase III Clinical Trial to Evaluate the Efficacy and Safety of TQB2450 Injection Combined With Anlotinib Hydrochloride Capsules Versus Pembrolizumab Injection as a First-line Treatment on Patient With Advanced NSCLC.
Overview
- Phase
- Phase 3
- Intervention
- TQB2450 injection
- Conditions
- Non Small Cell Lung Cancer
- Sponsor
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- Enrollment
- 375
- Locations
- 15
- Primary Endpoint
- Disease progression-free survival(PFS) evaluated by Independent Review Committee (IRC)
- Last Updated
- 4 years ago
Overview
Brief Summary
A clinical study to evaluate the efficacy and safety of TQB2450 injection combined with Anlotinib Hydrochloride capsules versus K drug as a first-line treatment of advanced non-small cell lung cancer.A total of 375 subjects will be enrolled.
Investigators
Eligibility Criteria
Inclusion Criteria
- •According to the 8th edition of the International Association for the Study of Lung Cancer and the American Joint Committee on Cancer Classification, the tumor node metastasis (TNM) staging of lung cancer is locally advanced (stage ⅢB/ⅢC), metastatic or recurrent ( Stage IV) NSCLC patients. (Note: Mixed tumors will be classified according to the main cell type; if there are small cell components, the subject is unqualified).
- •Between the ages of 18-75 years (calculated based on the date of signing ICF); male or female; Eastern cooperative oncology group (ECOG) score 0-1; estimated survival time ≥ 3 months.
- •According to the RECIST 1.1 standard, there is at least one measurable lesion. If the measurable lesion is located in the radiotherapy area, it should be clearly defined as a progressive state.
- •Patients who have not received systemic anti-tumor therapy for advanced, recurrent or metastatic diseases in the past. For those who have received adjuvant chemotherapy in the past, the interval between the recurrence time and the last adjuvant chemotherapy should be at least 6 months; The interval between the end of previous radiotherapy for chest and this treatment should be more than 6 months, and the interval between palliative radiotherapy for chest and this treatment should be more than 7 days.
- •Tumor tissue slices that have not undergone radiotherapy at or after the diagnosis of advanced or metastatic NSCLC must be provided. Tumor tissue samples must be archived samples or fresh samples obtained within 12 months before randomization, and the proportion of programmed death-Ligand 1(PD-L1) positive tumor cells≥ 1% (TPS ≥ 1%).
- •For non-squamous NSCLC, patients with no epidermal growth factor receptor (EGFR) mutations and ALK fusions (for squamous NSCLC, patients with known EGFR mutations and anaplastic Lymphoma kinase (ALK) fusions need to be excluded, and those with unknown status are not mandatory to be tested).
- •The function of main organs are well and meet the following standards:
- •a. Routine blood examination standards (without blood transfusion or correction with hematopoietic stimulating factor drugs within 14 days before screening): i. Absolute neutrophil count (ANC) ≥1.5×109 /L; ii. Platelets ≥100×109 /L; iii. Hemoglobin ≥90 g/L. b. The blood biochemical examination shall meet the following standards: i. Total bilirubin (TBIL) ≤ 2 × upper limit of normal (ULN) (Patients with Gilbert syndrome ≤ 3 × ULN); ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤2.5×ULN. If it is accompanied by liver metastasis, ALT and AST≤5×ULN; iii. Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance estimated by Cockcroft-Gault glomerular filtration formula ≥60 mL/min; iv. Serum albumin (ALB) ≥30g/L. c. Urine routine examination standard: urine routine indicates urine protein \<++; if urine protein ≥++, it is necessary to confirm that the 24-hour urine protein quantitative ≤1.0 g.
- •d. Blood coagulation test standards: prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR)≤1.5×ULN (no anticoagulant therapy).
- •e. Thyroid Stimulating Hormone (TSH) ≤ ULN; if abnormal, T3 and T4 levels should be examined. If T3 and T4 levels are normal, it can be selected.
Exclusion Criteria
- •Tumor disease and medical history:
- •Brain metastases without local treatment; Note: Subjects who have previously received brain metastasis therapy and meet all the following criteria can participate in this study: i. Only supratentorial and cerebellar metastases; ii. The condition needs to be stable for ≥4 weeks and no new brain metastases or brain metastases are found Expanded imaging evidence; iii. The subject must have stopped corticosteroids/dehydrator for at least 2 weeks before starting to use the trial drug;
- •There are midbrain, pons, medulla oblongata, spinal cord and meningeal metastases；
- •Other malignant tumors appeared or were present within 3 years. The following two cases can be included: other malignant tumors treated by single operation have achieved 5-year Disease-free survival (DFS) in a row; The cured cervical carcinoma in situ, non melanoma skin cancer and superficial bladder tumor \[ta (non-invasive tumor), tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)\];
- •Central type, cavity squamous cell carcinoma (primarily in the main bronchus and around the hilar);
- •Imaging shows that the tumor invades large blood vessels or is unclearly separated from the blood vessels, or the investigator judges that the tumor is likely to invade important blood vessels and cause fatal bleeding during the subsequent study(The major vessels in the chest include pulmonary aorta, left pulmonary artery, right pulmonary artery, four pulmonary veins, superior vena cava, inferior vena cava and aorta);
- •Severe bone injury caused by tumor bone metastasis, including pathological fracture of weight-bearing bone and spinal cord compression that occurred within 6 months or is expected to occur in the near future(Such as spine, pelvis, femur, tibia, phalanges, calcaneus, etc.);
- •Patients with serous cavity (thoracic cavity, abdominal cavity, or pericardial cavity) that require repeated drainage to relieve clinical symptoms (as determined by the investigator), or who have received drainage of serous cavity effusion for the purpose of treatment within 2 weeks before treatment.
- •Previous anti-tumor treatments:
- •Received the treatment of proprietary Chinese medicines with anti-tumor indications specified in the NMPA approved drug instructions within 2 weeks before the start of the study treatment(Including compound cantharidin capsules, Kangai injection, Kanglaite capsule/injection, Aidi injection, brucea javanica oil injection/capsule, Xiaoaiping tablet/injection, Huachansu capsule, etc.);
Arms & Interventions
TQB2450 injection + Anlotinib Hydrochloride capsules
TQB2450 injection: once every 3 weeks, 1200mg each time, intravenous infusion. Until the disease progression or unbearable adverse events occur. Anlotinib Hydrochloride capsules: once a day,12mg each time, oral administration before breakfast. Continuous administration for 2 weeks, withdrawal for 1 week, i.e. 3 weeks (21 days) as a course of treatment. Until the disease progression or unbearable adverse events occur.
Intervention: TQB2450 injection
TQB2450 injection + Anlotinib Hydrochloride capsules
TQB2450 injection: once every 3 weeks, 1200mg each time, intravenous infusion. Until the disease progression or unbearable adverse events occur. Anlotinib Hydrochloride capsules: once a day,12mg each time, oral administration before breakfast. Continuous administration for 2 weeks, withdrawal for 1 week, i.e. 3 weeks (21 days) as a course of treatment. Until the disease progression or unbearable adverse events occur.
Intervention: Anlotinib Hydrochloride Capsules
Pembrolizuma injection + placebo of Anlotinib hydrochloride capsules
Pembrolizumab injection: once every 3 weeks, 200mg each time, intravenous infusion. Until the disease progression or unbearable adverse events occur. Placebo of Anlotinib hydrochloride capsules:once a day, 0mg each time, oral administration before breakfast. Continuous administration for 2 weeks, withdrawal for 1 week, i.e. 3 weeks (21 days) as a course of treatment. Until the disease progression or unbearable adverse events occur.
Intervention: Pembrolizumab injection
Pembrolizuma injection + placebo of Anlotinib hydrochloride capsules
Pembrolizumab injection: once every 3 weeks, 200mg each time, intravenous infusion. Until the disease progression or unbearable adverse events occur. Placebo of Anlotinib hydrochloride capsules:once a day, 0mg each time, oral administration before breakfast. Continuous administration for 2 weeks, withdrawal for 1 week, i.e. 3 weeks (21 days) as a course of treatment. Until the disease progression or unbearable adverse events occur.
Intervention: Placebo
Outcomes
Primary Outcomes
Disease progression-free survival(PFS) evaluated by Independent Review Committee (IRC)
Time Frame: Baseline to up to two years
The period from the first use of the drug to disease progression or death (whichever occurs first)
Secondary Outcomes
- Objective response rate (ORR) evaluated by investigators(Baseline to up to two years)
- Overall survival (OS)(Baseline to up to two years)
- Disease Control Rate (DCR)(Baseline to up to two years)
- OS rate of 12 months(Baseline to up to two years)
- Disease PFS evaluated by investigators(Baseline to up to two years)
- Duration of response (DOR)(Baseline to up to two years)
- DOR rate (≥ 6 months) (the proportion of subjects with DOR ≥ 6 months)(Baseline to up to two years)
- Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)，as well as abnormal laboratory examination indicators.(Baseline to up to two years)