Study to Evaluate the Efficacy and Safety of Camrelizumab and Apatinib in Patients With GC/GEJC

Study Overview
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Brief Summary
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This is a study for participants with advanced gastric or gastroesophageal junction adenocarcinoma who have had tumor progression after first-line platinum-contained therapy. The primary study hypotheses are that camrelizumab (SHR-1210) combined with apatinib prolongs overall survival (OS) for participants with tumors that show positive programmed cell death ligand 1 (PD-L1) expression.

Official Title
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A Study of Camrelizumab (SHR-1210) Combined With Apatinib Versus Paclitaxel or Irinotecan in Participants With Advanced Gastric/Gastroesophageal Junction Adenocarcinoma Progressed After First-line Chemotherapy

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: camrelizumab
* Drug: Apatinib Mesylate
* Drug: Paclitaxel
* Drug: Irinotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically- or cytologically-confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma. Confirmed metastatic or locally advanced, unresectable disease. Progression on or after prior first-line therapy containing any platinum/fluoropyrimidine or platinum/taxane doublet. Willing to provide tumor tissue for PD-L1 biomarker analysis. Human epidermal growth factor receptor 2 (HER-2/neu) status known and participants with HER2/neu positive tumors show documentation of previous treatment containing trastuzumab. ECOG performance status of 0 to 1. Life expectancy of more than 12 weeks. Signing the informed consent forms. Adequate bone marrow, liver and renal function. Exclusion Criteria: Squamous cell or undifferentiated gastric cancer. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. 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. Clinically significant cardiovascular and cerebrovascular diseases. Subjects with high blood pressure who cannot be controlled well with antihypertensive drugs. Previous digestive tract bleeding history within 3 months or evident gastrointestinal bleeding tendency. 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-CTLA-4 monoclonal antibody, and VEGFR small molecule inhibitor therapy. Prior systemic chemotherapy, radiotherapy and surgery within 4 weeks before the study drug administration, or any unresolved AEs > Common Terminology Criteria for Adverse Events (CTCAE) Grade 1.

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: camrelizumab (SHR-1210) combined with apatinib<br>Participants will receive camrelizumab on Day 1 and Day 15 of each 28-day cycle and apatinib mg/day up to 2 years. | Drug: camrelizumab<br>* 200 mg intravenous (IV) camrelizumab on Day 1 and Day 15 of each 28-day cycle.<br>* Other names: SHR-1210;Drug: Apatinib Mesylate<br>* 250 mg qd<br>|
| Active Comparator: Paclitaxel or Irinotecan<br>Participants receive paclitaxel on Days 1, 8, and 15 of each 28-day cycle, or irinotecan on Days 1 and 15 of each 28-day cycle. | Drug: Paclitaxel<br>* 80 mg/m^2 administered as IV infusion on Days 1, 8, and 15 of each 28-day cycle.<br>Drug: Irinotecan<br>* 180 mg/m^2 administered as IV infusion on Days 1, and 15 of each 28-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) in PD-L1 Positive Participants. | OS was defined as the time from randomization to death due to any cause. | Up to 27 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) in All Participants. | OS was defined as the time from randomization to death due to any cause. | Up to 27 months | 
| Progression-free Survival (PFS) According to RECIST 1.1 base on investigator assessment in All Participants or in PD-L1 Positive Participants. | PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on investigator assessment, or death due to any cause, whichever occurs first. | Up to 27 months | 
| Time to Tumor Progression (TTP) According to RECIST 1.1 based on investigator assessment in All Participants or in PD-L1 Positive Participants. | TTP was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on investigator assessment in All Participants. | Up to 27 months | 
| Time to Failure (TTF) in All Participants or in PD-L1 Positive Participants | TTF was defined as the time from randomization to treatment discontinuation caused by any reason. | Up to 27 months | 
| Objective Response Rate (ORR) According to RECIST 1.1 based on investigator assessment in All Participants or in PD-L1 Positive Participants. | ORR was defined as the percentage of the participants in the analysis population who had a confirmed CR or PR according to RECIST 1.1 based on investigator assessment. | Up to 27 months | 
| Duration of Response (DOR) According to RECIST 1.1 Based on investigator assessment in All Participants or in PD-L1 Positive Participants. | DOR was defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. | Up to 27 months | 
| Disease Control Rate (DCR) According to RECIST 1.1 based on investigator assessment in All Participants or in PD-L1 Positive Participants. | DCR was defined as the percentage of the participants in the analysis population who had a confirmed CR or PR or SD according to RECIST 1.1 based on investigator assessment. | Up to 27 months | 
| Time to Response (TTR) According to RECIST 1.1 based on investigator assessment in All Participants or in PD-L1 Positive Participants. | TTR was defined as the time from randomization to the first documented evidence of CR or PR. | Up to 27 months | 
| The incidence and severity of adverse events (AEs) and serious adverse events (SAEs) as assessed by CTCAE v4.03. | The incidence and severity of adverse events (AEs) and serious adverse events (SAEs) as assessed by CTCAE v4.03. | Up to 27 months | 
| Proportion of dose suspension, dose reduction or dose discontinuation caused by treatment-related toxicities. | Proportion of dose suspension, dose reduction or dose discontinuation caused by treatment-related toxicities. | Up to 27 months | 
| Proportion of anti-camrelizumab antibody (ADA) and neutralizing antibody (Nab) formed during the study from baseline | Proportion of anti-camrelizumab antibody (ADA) and neutralizing antibody (Nab) formed during the study from baseline | Up to 27 months | 
| Serum concentration of camrelizumab | Serum concentration of camrelizumab | Up to 27 months | 
| Plasma concentration of apatinib | plasma concentration of apatinib | Up to 27 months |