A Study of TQB2450 in Subjects With Stage III Non-Small Cell Lung Cancer(NSCLC)

Study Overview
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Brief Summary
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This study is a randomized, double-blind, double-dummy,placebo parallel controlled, multi-centre,phase III clinical trial to evaluate the efficacy and safety of TQB2450 with or without anlotinib compared with placebo as consolidation treatment in subjects with locally advanced/unresectable (Stage III) Non-Small Cell Lung Cancer that has not progressed after prior concurrent/sequential chemoradiotherapy.

Official Title
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A Randomized, Double-blind and Imitation, Placebo Parallel Control, Multicentre Phase III Study of TQB2450 With or Without Anlotinib as Consolidation Treatment in Subjects With Locally Advanced/Unresectable (Stage III) Non-Small Cell Lung Cancer That Have Not Progressed After Prior Concurrent/Sequential Chemoradiotherapy

Conditions
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Stage III Non-small-cell Lung Cancer

Intervention / Treatment
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* Drug: TQB2450
* Drug: Anlotinib
* Drug: TQB2450(blank)
* Drug: Anlotinib(blank)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-75 years old ; Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; Life expectancy ≥ 3 months. Histologically or cytologically confirmed unresectable (Stage III) Non-Small Cell Lung Cancer. At least has one measurable lesion before radiotherapy. At least has one type of platinum-containing chemotherapy, Absence of progression after concurrent/sequential chemoradiotherapy. Adequate laboratory indicators. No pregnant or breastfeeding women, and a negative pregnancy test. Understood and signed an informed consent form. Exclusion Criteria: Squamous cell carcinoma meets following conditions should be excluded: Cavernous lung cancer. Has hemoptysis and maximum daily hemoptysis volume ≥ 2.5ml within 1 month before the first administration. Has received anti-angiogenic drugs or other PD-1 / PD-L1 / CTLA-4 antibody therapy or other immunotherapy against PD-1 / PD-L1 / CTLA-4. Severe hypersensitivity occurs after administration of other monoclonal antibodies. Diagnosed and/or treated additional malignancy within 5 years with the exception of cured basal cell carcinoma of skin ,carcinoma in situ of prostate,and carcinoma in situ of cervix. Pathologically confirmed mixed small cell and non-small cell lung cancer. EGFR gene mutations. Has any active autoimmune disease or history of autoimmune disease. After the early stage of chemoradiotherapy, the treatment toxicity ≥ grade 2 is not fully alleviated. Has ≥grade 2 pneumonia. Immunosuppressant or systemic or absorbable local hormone therapy is required to achieve the aim of immunosuppression (dose &gt; 10mg/ day prednisone or other therapeutic hormones) and is still used within 2 weeks after the first administration. Has multiple factors affecting oral medication. Has active bleeding or a persistent decrease in hemoglobin. Has any bleeding or bleeding events ≥grade 3 in the first 4 weeks before the first administration. 2.Has received anti-angiogenic drugs or other PD-1 / PD-L1 / CTLA-4 antibody therapy or other immunotherapy against PD-1 / PD-L1 / CTLA-4. 14. Has unhealed wounds, fractures, active gastric and duodenal ulcers, positive continuous fecal occult blood, ulcerative colitis in the first 4 weeks before the first administration. 15. Has received NMPA approved anti-tumor drugs or immunomodulatory drugs for systemic treatment within 2 weeks before the first administration. 16.Has a history of a hematological system transplantation or organ transplantation. 17. Has active diverticulitis、peritoneal abscess, intestinal obstruction. 18. Has any serious and/or uncontrollable disease. 19. According to the judgement of the investigators, there are other factors that may lead to the termination of the study.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TQB2450+Anlotinib<br>TQB2450 1200 mg administered intravenously (IV) on Day 1 of each 21-day cycle ,Anlotinib capsules 8 mg given orally, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21). | Drug: TQB2450<br>* TQB2450 is a humanized monoclonal antibody targeting programmed death ligand-1 (PD-L1), which prevents PD-L1 from binding to PD-1 and B7.1 receptors on T cell surface, restores T cell activity, thus enhancing immune response and has potential to treat various types of tumors.<br>Drug: Anlotinib<br>* a multi-target receptor tyrosine kinase inhibitor<br>|
| Experimental: TQB2450+Anlotinib(blank)<br>TQB2450 1200 mg administered intravenously (IV) on Day 1 of each 21-day cycle ,Anlotinib capsules 0 mg given orally, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21). | Drug: TQB2450<br>* TQB2450 is a humanized monoclonal antibody targeting programmed death ligand-1 (PD-L1), which prevents PD-L1 from binding to PD-1 and B7.1 receptors on T cell surface, restores T cell activity, thus enhancing immune response and has potential to treat various types of tumors.<br>Drug: Anlotinib(blank)<br>* Subjects administrated anlotinib (blank) in fasting conditions, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21)<br>|
| Placebo Comparator: TQB2450(blank)+Anlotinib(blank)<br>TQB2450 0 mg administered intravenously (IV) on Day 1 of each 21-day cycle ,Anlotinib capsules 0 mg given orally, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21). | Drug: TQB2450(blank)<br>* Subjects administrated TQB2450 (blank) intravenously (IV) on Day 1 of each 21-day<br>Drug: Anlotinib(blank)<br>* Subjects administrated anlotinib (blank) in fasting conditions, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) evaluated by Independent Review Committee(IRC) | PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause, based on IRC. | up to 33 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS evaluated by Investigator | PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause, based on investigator. | up to 33 months | 
| Overall survival (OS) | OS defined as the time from randomization to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive. | up to 5 years | 
| Overall response rate (ORR) | Percentage of participants achieving complete response (CR) and partial response (PR). | up to 33 months | 
| Disease control rate（DCR） | Percentage of participants achieving complete response (CR) and partial response (PR) and stable disease (SD). | up to 33 months | 
| Duration of response（DOR） | The time when the participants first achieved complete or partial remission to disease progression. | up to 33 months | 
| PFS rate at month 6 | The percentage of PFS at month 6 | up to 6 months | 
| PFS rate at month 12 | The percentage of PFS at month 12 | up to 12 months | 
| Biomarkers, such as PD-L1 expression, etc. | Tissue samples were collected during the screening period for pd-l1 analysis. Blood samples were collected for Tumor Mutation Burden (TMB) test before enrollment (within 7 days before medication) and after exit (±3 days). | up to 33 months | 
| Immunogenicity, such as the incidence of ADA | Degree of the immune response caused by the drug. | on day 1, 42, 105, 189 and 90 days after the last administration. |