Evaluation of the Efficacy and Safety of AL2846 Capsule Combined With TQB2450 Injection Compared to Docetaxel Injection in Advanced Non-small Cell Lung Cancer Patients Who Have Failed With Immunotherapy.

Study Overview
=================
Brief Summary
-----------------
To investigate the efficacy of AL2846 capsules in combination with TQB2450 injection or Docetaxel injection in patients with advanced NSCLC who have previously failed immune checkpoint inhibitors (anti-PD-1 monoclonal antibody, anti-PD-L1 monoclonal antibody), regardless of new anti-tumor treatment and early termination of treatment.

Official Title
-----------------
A Multicenter, Randomized, Double-blind, Parallel-controlled Phase III Clinical Trial to Evaluate the Efficacy and Safety of AL2846 Capsules Combined With TQB2450 Injection Compared With Docetaxel Injection in Patients With Advanced Non-small Cell Lung Cancer Who Have Failed With Immunotherapy.

Conditions
-----------------
Non-small Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: TQB2450 injection, docetaxel injection matching placebo, AL2846 capsules
* Drug: TQB2450 matching placebo, docetaxel injection, AL2846 matching placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age: 18-75 years; Eastern Eastern Cooperative Oncology Group performance status (ECOG PS) score: 0-1; BMI ≥ 17 at baseline; Patients with histologically or cytologically confirmed inoperable and inoperable locally advanced (stage IIIB/IIIC), metastatic or recurrent (stage IV) nonsmall-cell lung cancer (NSCLC) who cannot receive radical concurrent chemoradiotherapy; Failure of platinum-based chemotherapy and immune checkpoint inhibitors for incurable locally advanced or metastatic or recurrent NSCLC; Number of lines of prior systemic therapy received for locally advanced or metastatic/recurrent disease that is unresectable/not amenable to radical chemoradiation; Adequate major organ function; Exclusion Criteria: Patients who had or currently had other malignant tumors within 3 years; Presence of:epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) fusion, c-ros oncogene 1 (ROS1) fusion and other significant driver gene mutations; Factors affecting oral drugs; Major surgical treatment, incisional biopsy or obvious traumatic injury and long-term uncured wound or fracture within 28 days before the start of study treatment; Hyperactive/venous thrombotic events within 6 months; Subjects with any severe and/or uncontrolled disease; Previously received other immunotherapy and Research Advance of Small Molecular Targeted Anti-Tumor Agents Tyrosine kinase inhibitors (TKIs); According to the investigator's judgment, there are concomitant diseases that seriously endanger the subject's safety or affect the completion of the study, or there are other reasons that are not suitable for the subject;

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TQB2450 injection + docetaxel injection matching placebo + AL2846 capsules<br>TQB2450 injection combined with docetaxel injection matching placebo and AL2846 capsules 21 days as a treatment cycle. | Drug: TQB2450 injection, docetaxel injection matching placebo, AL2846 capsules<br>* AL2846 capsules is a multi-targeted small molecule receptor tyrosine kinase inhibitor. TQB2450 Injection is an anti-programmed death-1 (PD-L1).<br>|
| Active Comparator: TQB2450 matching placebo + docetaxel injection + AL2846 matching placebo<br>TQB2450 matching placebo combined with docetaxel injection and AL2846 matching placebo 21 days as a treatment cycle. | Drug: TQB2450 matching placebo, docetaxel injection, AL2846 matching placebo<br>* Docetaxel injection is a type of chemotherapy for treatment of different types of cancer.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | The time from randomization to the date of death from any cause. | From randomization to the time of death from any cause, assessed up to 36 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) by investigator assessment | Time from randomization to objective disease progression or death from any cause, whichever occurs first. | From the date of randomization to the date of first recorded progression or death from any cause, whichever comes first, assessed up to 36 months. | 
| Objective response rate (ORR) | Refers to the percentage of subjects with complete response (CR) or partial response (PR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1. | Time from the date of randomization to the first recorded complete remission (CR) or partial remission (PR), assessed up to 36 months. | 
| Disease Control Rate (DCR) | Refers to the percentage of subjects with complete response (CR), partial response (PR) or stable disease (SD) ≥ 6 weeks as determined by the investigator according to RECIST 1.1. | Baseline up to CR or PR or 6 weeks, whichever came first. | 
| Duration of response (DOR) | For subjects with a best response of complete response (CR) or partial response (PR), it is defined as the time from the date of first documentation of tumor response to the date of first documentation of disease progression or death due to any cause, whichever occurs first. | From the date of first documentation of tumor response to the date of first documentation of disease progression or death due to any cause, whichever occurs first, assessed up to 36 months. | 
| 12-month survival rate (12-month OS rate) | The survival curve corresponds to the cumulative survival rate at 12 months | Baseline up to 12-month | 
| Health Questionnaire Form | Questionnaire: pain score：Place a check in the space that best reflects patients' health for the day. | During the screening period, the second cycle and other even numbered cycles, each cycle is 21 days, assessed up to 36 months. | 
| Effects on subjects' health-related quality of life | Questionnaire: Quality of life related scale (The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 3rd edition).For questions 1 to 28, choose a number from 1 to 4, 1 means none and 4 means very good. For questions 29 and 30, choose a number from 1 to 7, with 1 being very poor and 7 being very good. | During the screening period, the second cycle and other even numbered cycles, each cycle is 21 days, assessed up to 36 months. | 
| Patients with abnormal laboratory inspection indicators | Laboratory inspection indicators exceed the normal range | From signing the informed consent form to the 30 days after the last dose. | 
| Adverse event rate | The occurrence of all adverse events (AEs), serious adverse events (SAEs) and treatment-related adverse events (TEAEs). | From signing the informed consent form to the 30 days after the last dose. | 
| Occurrence of anti-drug antibody (ADA) | Occurrence of ADA immunoglobulin | Pre-dose in cycle 1, cycle 2, cycle 5, cycle 9, 90 days after administration, each cycle is 21 days. | 
| Occurrence of neutralizing antibody (Nab) | Antibody preventing cells from being invaded by an antigen or infectious agent. | Pre-dose in cycle 1, cycle 2, cycle 5, cycle 9, 90 days after administration, each cycle is 21 days. |