Gastric Cancer, GastroEsophageal Cancer
Conditions
Keywords
PD-1, SHR-1210, Capecitabine, Oxaliplatin, Apatinib
Brief summary
The purpose of this trial is to estimate overall response rate (ORR) of SHR-1210 combined with capecitabine and oxaliplatin or with apatinib as first-line treatment in subjects with locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Detailed description
Approximately 110 participants will be assigned to SHR-1210 + capecitabine + oxaliplatin combination therapy (Cohort 1), or SHR-1210 + apatinib combination therapy (Cohort 2).
Interventions
BIOLOGICALSHR-1210
SHR-1210 is a humanized anti-PD1 IgG4 monoclonal antibody
DRUGCapecitabine
1000 mg/m\^2 administered as continuous oral twice daily (BID) of each 3-week cycle.
DRUGOxaliplatin
130 mg/m\^2 administered IV Q3W on Day 1 of each 3-week cycle.
DRUGApatinib
375 mg administered as continuous oral once daily (QD) of each 3-week cycle.
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has histologically- or cytologically-confirmed diagnosis of locally advanced unresectable or metastatic 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 HER2 inhibitor). Subjects with previous adjuvant/neo-adjuvant therapy completed more than 6 months can be enrolled. * Has measurable disease per RECIST 1.1. * Life expectancy ≥ 12 weeks. * 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 received prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody, or a VEGFR inhibitor. * Has known active central nervous system metastases. * Has received a live vaccine within 4 weeks prior to the first dose of study treatment. * With any active autoimmune disease or history of autoimmune disease, including but not limited to the following: hepatitis, 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. * 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), or ventricular arrhythmia which need medical intervention. * Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents(within 3 months): systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg. * Coagulation abnormalities (INR \> 1.5 or APTT \> 1.5×ULN), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Up to approximately 6 months. | ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) Per RECIST 1.1 | Up to 24 months. | PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded independent central review or death due to any cause, whichever occurs first. |
| Duration of Response (DOR) Per RECIST 1.1 | Up to 24 months. | For participants who demonstrate CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters), DOR is defined as the time from first documented evidence of CR or PR until disease progression per RECIST 1.1 based on assessments by blinded independent central review or death due to any cause, whichever occurs first. |
| Disease Control Rate (DCR) Per RECIST 1.1 | Up to 24 months. | DCR is defined as the percentage of participants in the analysis population who have a CR, PR or SD per RECIST 1.1. |
| Number of Subjects With Treatment-related Adverse Events (AEs) | Up to 24 months. | Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Participants received SHR-1210 200 mg, intravenously (IV) every 3 weeks(Q3W) plus capecitabine 1000 mg/m\^2 twice daily (BID) by continuous oral administration 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 375 mg PO qd if there was no PD. | 48 |
| Cohort 2 Participants received SHR-1210 200 mg, intravenously (IV) every 3 weeks(Q3W) plus apatinib 375 mg daily (QD) continuous oral administration of each 3-week cycle. | 19 |
| Total | 67 |
Baseline characteristics
| Characteristic | Cohort 1 | Total | Cohort 2 |
|---|---|---|---|
| Age, Continuous | 56.0 Years old | 59.0 Years old | 62.0 Years old |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 48 Participants | 67 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 48 participants | 67 participants | 19 participants |
| Sex: Female, Male Female | 37 Participants | 53 Participants | 16 Participants |
| Sex: Female, Male Male | 11 Participants | 14 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 14 / 48 | 9 / 19 |
| other Total, other adverse events | 48 / 48 | 19 / 19 |
| serious Total, serious adverse events | 22 / 48 | 12 / 19 |
Outcome results
Primary
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1.
Time frame: Up to approximately 6 months.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 58.3 percentage |
| Cohort 2 | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 10.5 percentage |
Secondary
Disease Control Rate (DCR) Per RECIST 1.1
DCR is defined as the percentage of participants in the analysis population who have a CR, PR or SD per RECIST 1.1.
Time frame: Up to 24 months.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Disease Control Rate (DCR) Per RECIST 1.1 | 93.8 percentage |
| Cohort 2 | Disease Control Rate (DCR) Per RECIST 1.1 | 57.9 percentage |
Secondary
Duration of Response (DOR) Per RECIST 1.1
For participants who demonstrate CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters), DOR is defined as the time from first documented evidence of CR or PR until disease progression per RECIST 1.1 based on assessments by blinded independent central review or death due to any cause, whichever occurs first.
Time frame: Up to 24 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Duration of Response (DOR) Per RECIST 1.1 | 5.749 months |
| Cohort 2 | Duration of Response (DOR) Per RECIST 1.1 | NA months |
Secondary
Number of Subjects With Treatment-related Adverse Events (AEs)
Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03.
Time frame: Up to 24 months.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Number of Subjects With Treatment-related Adverse Events (AEs) | 48 participants |
| Cohort 2 | Number of Subjects With Treatment-related Adverse Events (AEs) | 18 participants |
Secondary
Progression-free Survival (PFS) Per RECIST 1.1
PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded independent central review or death due to any cause, whichever occurs first.
Time frame: Up to 24 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Progression-free Survival (PFS) Per RECIST 1.1 | 6.768 months |
| Cohort 2 | Progression-free Survival (PFS) Per RECIST 1.1 | 2.793 months |