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

• ClinicalTrials.gov Identifier: NCT04342910
• Recruitment Status: Recruiting
• First Posted: April 13, 2020
• Last Update Posted: November 18, 2020
• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Information provided by (Responsible Party): Jiangsu HengRui Medicine Co., Ltd.

Tracking Information

• First Submitted Date: April 9, 2020
• First Posted Date: April 13, 2020
• Last Update Posted Date: November 18, 2020
• Actual Study Start Date: September 21, 2020
• Estimated Primary Completion Date: April 1, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 10, 2020)

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

OS was defined as the time from randomization to death due to any cause.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 10, 2020)

• Overall Survival (OS) in All Participants. [ Time Frame: Up to 27 months ]
  OS was defined as the time from randomization to death due to any cause.
• 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 ]
  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.
• 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 ]
  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.
• Time to Failure (TTF) in All Participants or in PD-L1 Positive Participants [ Time Frame: Up to 27 months ]
  TTF was defined as the time from randomization to treatment discontinuation caused by any reason.
• 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 ]
  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.
• 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 ]
  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.
• 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 ]
  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.
• 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 ]
  TTR was defined as the time from randomization to the first documented evidence of CR or PR.
• 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 ]
  The incidence and severity of adverse events (AEs) and serious adverse events (SAEs) as assessed by CTCAE v4.03.
• Proportion of dose suspension, dose reduction or dose discontinuation caused by treatment-related toxicities. [ Time Frame: Up to 27 months ]
  Proportion of dose suspension, dose reduction or dose discontinuation caused by treatment-related toxicities.
• Proportion of anti-camrelizumab antibody (ADA) and neutralizing antibody (Nab) formed during the study from baseline [ Time Frame: Up to 27 months ]
  Proportion of anti-camrelizumab antibody (ADA) and neutralizing antibody (Nab) formed during the study from baseline
• Serum concentration of camrelizumab [ Time Frame: Up to 27 months ]
  Serum concentration of camrelizumab
• Plasma concentration of apatinib [ Time Frame: Up to 27 months ]
  plasma concentration of apatinib

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Gastric Cancer

Intervention

• Drug: camrelizumab
  200 mg intravenous (IV) camrelizumab on Day 1 and Day 15 of each 28-day cycle.
  Other Name: SHR-1210
• 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.

Study Arms

• Experimental: camrelizumab (SHR-1210) combined with apatinib
  Participants will receive camrelizumab on Day 1 and Day 15 of each 28-day cycle and apatinib mg/day up to 2 years.
  Interventions:

  • Drug: camrelizumab
  • Drug: Apatinib Mesylate
• Active Comparator: Paclitaxel or Irinotecan
  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.
  Interventions:

  • Drug: Paclitaxel
  • Drug: Irinotecan

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 10, 2020): 550
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 1, 2022
• Estimated Primary Completion Date: April 1, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Histologically- or cytologically-confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma.
2. Confirmed metastatic or locally advanced, unresectable disease.
3. Progression on or after prior first-line therapy containing any platinum/fluoropyrimidine or platinum/taxane doublet.
4. Willing to provide tumor tissue for PD-L1 biomarker analysis.
5. 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.
6. ECOG performance status of 0 to 1.
7. Life expectancy of more than 12 weeks.
8. Signing the informed consent forms.
9. Adequate bone marrow, liver and renal function.

Exclusion Criteria:

1. Squamous cell or undifferentiated gastric cancer.
2. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
3. 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.
4. Clinically significant cardiovascular and cerebrovascular diseases.
5. Subjects with high blood pressure who cannot be controlled well with antihypertensive drugs.
6. Previous digestive tract bleeding history within 3 months or evident gastrointestinal bleeding tendency.
7. 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.
8. Subjects who have previously received anti-PD-1 / PD-L1 monoclonal antibody, anti-CTLA-4 monoclonal antibody, and VEGFR small molecule inhibitor therapy.
9. 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Quanren Wang, Ph.D; wangquanren@hrglobe.cn

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04342910
• Other Study ID Numbers: SHR-1210-III-316
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Jiangsu HengRui Medicine Co., Ltd.
• Study Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jianming Xu, Ph.D; Affiliated Hospital, Academy of Military Medical Sciences

• PRS Account: Jiangsu HengRui Medicine Co., Ltd.
• Verification Date: April 2020