A Study to Evaluate SHR-1210 in Combination With Capecitabine + Oxaliplatin Sequenced by SHR-1210 + Apatinib as First-line Therapy in Treatment of Advanced Gastric Cancer

A Randomized, Multicenter, Open-Label, Phase 3 Study Comparing the Efficacy and Safety of SHR-1210 Plus Capecitabine and Oxaliplatin Sequenced by Apatinib With or Without SHR-1210 Versus Capecitabine and Oxaliplatin in Subjects With Previously Untreated Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer

This is a randomized, open-label, multi-center, phase III trial to evaluate the efficacy and safety of SHR-1210 plus capecitabine and oxaliplatin sequenced by apatinib with or without SHR-1210 versus capecitabine and oxaliplatin as first-line therapy in patients with locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Study Overview

• Status: Active, not recruiting
• Conditions: Gastric Cancer; GastroEsophageal Cancer
• Intervention / Treatment: Drug: SHR-1210; Drug: Capecitabine; Drug: Oxaliplatin; Drug: Apatinib

• Study Type: Interventional
• Enrollment (Actual): 887
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Beijing Cancer Hospital, Peking University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Has histologically- or cytologically-confirmed diagnosis of locally advanced unresectable or mestastatic adenocarcinoma of stomach or the esophagogastric junction (GEJ)
• Age ≥ 18 years old, male or female
• NO previous therapy for advanced/metastatic disease of GC/GEJ (including HER-2 inhibitor). Subjects with previous adjuvant/neo-adjuvant therapy completed more than 6 months can be enrolled.
• Has measurable disease per RECIST 1.1
• Eastern Cooperative Group (ECOG) performance status of 0 to 1
• Has adequate organ function
• Females of childbearing potential (FOCBP), who are not surgically sterile or postmenopausal, must conduct pregnancy test (serum or urine) within 7 days before enrollment, and must not be pregnant or breast-feeding women. If the result is negative, she must agree to use adequate contraception during the experiment and 3 months after the last administration of the test drugs. And non-sterilized males who are sexually active must agree to use adequate contraception during the experiment and 3 months after the last administration of the test drugs.

Exclusion Criteria:

• Has known HER2-positive status
• Has known active central nervous system metastatases
• Has received a live vaccine within 4 weeks prior to the first dose of study treatment
• With any acitve autoimmune disease or history of autoimmune disease, including but not limited to the following: hepatititis, pneumonitis, uveitis, colitis (inflammatory bowel disease), hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy. Asthma that requires intermittent use of bronchodilators or other medical intervention should also be excluded.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody, or a VEGFR inhibitor.
• Clinically significant cardiovascular and cerebrovascular diseases, including but not limited to severe acute myocardial infarction within 6 months before enrollment, unstable or severe angina, Congestive heart failure (New York heart association (NYHA) class > 2), orventricular arrhythmia which need medical intervention.
• Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents: systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: A; Participants receive SHR-1210 200 mg, intravenously (IV) every 3 weeks(Q3W) plus capecitabine 1000 mg/m^2 twice daily (BID) by continous oral adminstration for 14 days, followed by a recovery period of 7 days, plus oxaliplatin 130 mg/m^2, IV q3w; for 4-6 cycles followed by SHR-1210 plus apatinib 250 mg PO qd.	Drug: SHR-1210; Subjects receive SHR-1210 intravenously, Dosage form: lyophilised powder, Strength: 200 mg /vial; Drug: Capecitabine; 1000 mg/m^2 administered as continuous oral twice daily (BID) of each 3-week cycle.; Drug: Oxaliplatin; 130 mg/m^2 administered IV Q3W on Day 1 of each 3-week cycle.; Drug: Apatinib; 250 mg administered as continuous oral once daily (QD) of each 3-week cycle.
ACTIVE_COMPARATOR: B; Capecitabine 1000 mg/m^2 twice daily (BID) by continous oral adminstration for 14 days, followed by a recovery period of 7 days, plus Oxaliplatin 130 mg/m^2, IV q3w	Drug: Capecitabine; 1000 mg/m^2 administered as continuous oral twice daily (BID) of each 3-week cycle.; Drug: Oxaliplatin; 130 mg/m^2 administered IV Q3W on Day 1 of each 3-week cycle.
EXPERIMENTAL: C; Participants receive SHR-1210 200 mg, intravenously (IV) every 3 weeks(Q3W) plus capecitabine 1000 mg/m^2 twice daily (BID) by continous oral adminstration for 14 days, followed by a recovery period of 7 days, plus oxaliplatin 130 mg/m^2, IV q3w; for 4-6 cycles followed by SHR-1210	Drug: SHR-1210; Subjects receive SHR-1210 intravenously, Dosage form: lyophilised powder, Strength: 200 mg /vial; Drug: Capecitabine; 1000 mg/m^2 administered as continuous oral twice daily (BID) of each 3-week cycle.; Drug: Oxaliplatin; 130 mg/m^2 administered IV Q3W on Day 1 of each 3-week cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS) of SHR-1210 in combination with capecitabine + oxaliplatin sequenced by SHR-1210+apatinib versus capecitabine + oxaliplatin in all subjects or programmed cell death ligand 1 (PD-L1) positive participants	Up to 36 months after the first participant is randomized

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	Up to approximately 36 months
Progression-free Survival (PFS) per RECIST 1.1	Up to approximately 36 months
Number of Subjects with treatment-related adverse events (AEs)	Up to approximately 36 months

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 7, 2019
• Primary Completion (ANTICIPATED): February 1, 2022
• Study Completion (ANTICIPATED): March 1, 2023

Study Registration Dates

• First Submitted: January 20, 2019
• First Submitted That Met QC Criteria: January 20, 2019
• First Posted (ACTUAL): January 23, 2019

Study Record Updates

• Last Update Posted (ACTUAL): August 25, 2021
• Last Update Submitted That Met QC Criteria: August 24, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: PD-1; SHR-1210
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Protein Kinase Inhibitors; Capecitabine; Oxaliplatin; Apatinib
• Other Study ID Numbers: SHR-1210-III-311

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No