Camrelizumab Combined With Apatinib Mesylate or Camrelizumab Alone for First-line Treatment in Subjects With Programmed Death Ligand 1 (PD-L1) Positive Relapsed or Advanced Non-small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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The study is being conducted to evaluate the efficacy and safety of Camrelizumab (200mg,q2w) combined with Apatinib(250mg qd) in subjects with PD-L1 positive relapsed or advanced non-small cell lung cancer.

Official Title
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A Randomized, Open-Label, Controlled, Multicenter Phase III Study of Camrelizumab Combined With Apatinib Mesylate or Camrelizumab Alone Versus Platinum-based Chemotherapy for First-line Treatment in Subjects With PD-L1 Positive Relapsed or Advanced NSCLC

Conditions
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PD-L1 Positive Non-small Cell Lung Cancer

Intervention / Treatment
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* Biological: Camrelizumab 200mg
* Drug: Apatinib Mesylate 250mg
* Drug: Pemetrexed disodium for injection
* Drug: Paclitaxel injection
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who have recurrent or advanced (Stage IIIB-IV) non-small cell lung cancer confirmed by histology or cytology. No prior systemic treatment. Subjects who have received prior neo-adjuvant, adjuvant chemotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment free interval of at least 6 months from randomization since the last chemotherapy cycle. Subjects should not have a previously detected activating Epidermal Growth Factor Receptor (EFGR) mutation or Anaplastic Lymphoma Kinase (ALK) fusion oncogene. Subjects must have measurable disease by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) per RECIST 1.1 criteria; Freshly acquired samples or archived specimens within 6 months before randomization must be provided. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Exclusion Criteria: Radiologically confirmed central squamous cell carcinoma. Untreated central nervous system metastases (such as brain or meningeal metastases). Pleural effusion, pericardial effusion, or ascites with clinical symptoms that need drainage Past or present with idiopathic pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, tissue pneumonia (eg bronchitis, occlusive vasculitis), drug-induced pneumonia, active pneumonia during CT screening, or objective evidence of severe impairment of lung function Subjects with an active, known or suspected autoimmune disease. Patients with type I diabetes who are receiving a stable dose of insulin, hypothyroidism who only needs hormone replacement therapy, and skin diseases (such as eczema, vitiligo, or psoriasis) that do not require systemic treatment and do not have acute deterioration within 1 year before the screening period, are allowed. Subjects with suspected active tuberculosis should be examined for chest X-rays, sputum, and ruled out by clinical signs and symptoms. Uncontrolled Cardiac Symptoms or Diseases. Subjects with high blood pressure who cannot be controlled well with antihypertensive drugs (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg). Arterial / venous thrombosis events, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism, occurred within the first 6 months of randomization. Subjects who have previously received anti-PD-1 / PD-L1 monoclonal antibody, anti-cytotoxic T lymphocyte antigen-4 monoclonal antibody, or vascular endothelial growth factor receptor (VEGFR) small molecule inhibitor therapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Camrelizumab 200mg + Apatinib Mesylate 250mg<br>Camrelizumab 200mg q2w ivgtt+ Apatinib Mesylate 250mg once daily po qd | Biological: Camrelizumab 200mg<br>* Camrelizumab 200mg q2w ivgtt<br>Drug: Apatinib Mesylate 250mg<br>* Apatinib Mesylate 250mg po qd<br>|
| Experimental: Camrelizumab 200mg<br>Camrelizumab 200mg q2w ivgtt | Biological: Camrelizumab 200mg<br>* Camrelizumab 200mg q2w ivgtt<br>|
| Active Comparator: Pemetrexed/Paclitaxel injection+ Carboplatin<br>For non-squamous NSCLC: Pemetrexed disodium for injection + Carboplatin; For squamous NSCLC: Paclitaxel injection + Carboplatin | Drug: Pemetrexed disodium for injection<br>* Pemetrexed disodium for injection 500 mg/m2 q3w<br>Drug: Paclitaxel injection<br>* Paclitaxel injection 175 mg/m2 q3w<br>Drug: Carboplatin<br>* Carboplatin AUC 5 mg/mL/min q3w<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) assessed by Independent review committee (IRC) | Progression Free Survival, defined as the time from randomization to the first occurrence of disease progression as determined by IRC with use of Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or death from any cause, whichever occurs first. | up to 2 years | 
| Overall survival | Overall survival is the time interval from the date of randomization to death due to any reason or lost of follow-up | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS assessed by investigator | Progression-Free-Survival | up to 2 years | 
| Objective Response Rate | Objective Response Rate, determined using RECIST v1.1 criteria, defined as best overall response (complete or partial response) across all assessment time points | At the time point of every 6 weeks，up to 2 years | 
| Disease Control Rate | Disease Control Rate, determined using RECIST v1.1 criteria | At the time point of every 6 weeks，up to 2 years | 
| Duration of Response | Duration of Response, determined using RECIST v1.1 criteria | Up to 2 years | 
| Time to Treatment Failure | Time to Treatment Failure, defined as the time from randomization to treatment discontinuation. | Up to 2 years | 
| Adverse Events and Serious Adverse Events | Adverse Events and Serious Adverse Events | from the first drug administration to within 90 days for the last Camrelizumab dose |