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

Official title

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

Overview

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.

Interventions

• Drug camrelizumab
  200 mg intravenous (IV) camrelizumab on Day 1 and Day 15 of each 28-day cycle.
• Drug Apatinib Mesylate
  250 mg qd
• Drug Paclitaxel
  80 mg/m\^2 administered as IV infusion on Days 1, 8, and 15 of each 28-day cycle.
• Drug Irinotecan
  180 mg/m\^2 administered as IV infusion on Days 1, and 15 of each 28-day cycle.

Primary outcome measures

• Overall Survival (OS) in PD-L1 Positive Participants. [Time frame: Up to 27 months]

Secondary outcome measures (12)

• Overall Survival (OS) in All Participants. [Time frame: 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. [Time frame: 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. [Time frame: Up to 27 months]
• Time to Failure (TTF) in All Participants or in PD-L1 Positive Participants [Time frame: 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. [Time frame: 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. [Time frame: 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. [Time frame: 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. [Time frame: Up to 27 months]
• The incidence and severity of adverse events (AEs) and serious adverse events (SAEs) as assessed by CTCAE v4.03. [Time frame: Up to 27 months]
• Proportion of dose suspension, dose reduction or dose discontinuation caused by treatment-related toxicities. [Time frame: Up to 27 months]
• Proportion of anti-camrelizumab antibody (ADA) and neutralizing antibody (Nab) formed during the study from baseline [Time frame: Up to 27 months]
• Serum concentration of camrelizumab [Time frame: Up to 27 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Affiliated Hospital, Academy of Military Medical Sciences — Beijing

Identifiers

NCT: NCT04342910 · SHR-1210-III-316

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗