Study of HLX22 in Combanition With Trastuzumab and Chemotherapy Versus Placebo in Combination With Trastuzumab and Chemotherapy for Treatment of Locally Advanced or Metastatic Gastric Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the clinical efficacy and safety of HLX22 in the HER2+ Locally Adanved or Metastatic Gastric Cancer as the first-line therapy.This study consists of three periods, screening period (28 days), treatment period and follow-up period (including safety follow-up, survival follow-up).Subjects can be enrolled into this study only if they meet inclusion criteria and do not meet exclusion criteria. The enrolled subjects will receive an intravenous infusion of HLX22/placebo and SOC(standard of care: Trastuzumab + XELOX) once every 3 weeks until the loss of clinical benefit, death, intolerable toxicity, withdrawal of informed consent or other reasons as specified in the protocol(whichever occurs earlier).

Detailed Description
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HLX22(25mg/kg) or HLX22(15mg/kg) or placebo will be administered intravenously [IV] on day 1 of each 3-week cycle. Trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance dose) will be administered IV on day 1 of each 3-week cycle. SOC chemotherapy is XELOX (1000 mg/m^2 capecitabine administered orally twice daily [BID] on days 1-14 of each 3-week cycle and 130 mg/m^2 oxaliplatin administered IV on Day 1 of each 3-week cycle).

Official Title
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A Randomized, Double-blinded，Multicenter，Phase II Clinical Study of HLX22 (Recombinant Humanized Anti-HER2 Monoclonal Antibody Injection) in Combination With Trastuzumab and Chemotherapy (XELOX) Versus Placebo in Combination With Trastuzumab and Chemotherapy (XELOX) for Treatment of Locally Advanced or Metastatic Gastric Cancer (GC)

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: HLX22
* Drug: Placebo
* Drug: Trastuzumab
* Drug: Oxaliplatin
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic HER2 positive gastric adenocarcinoma. HER2-positive defined as either immunohistochemistry (IHC) 3+ or IHC 2+ in combination with in-situ hybridization positive (ISH+) or fluorescent in-situ hybridization (FISH), as assessed by central review on primary or metastatic tumor Has measurable disease as defined by RECIST 1.1 as determined by the IRRC Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale Has a life expectancy of greater than 6 months Has adequate organ function Exclusion Criteria: Has a known additional malignancy that is progressing or has required active treatment within the past 2 years Has history of HER2 targeted therapy Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 7 months after the last dose of trial treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HLX22(25mg/kg)+Trastuzumab + Chemotherapy (XELOX)<br>Participants receive 25mg/kg HLX22 IV every 3 weeks (Q3W) plus trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance thereafter) IV Q3W in combination with XELOX chemotherapy | Drug: HLX22<br>* IV Q3W D1<br>Drug: Trastuzumab<br>* IV Q3W D1<br>Drug: Oxaliplatin<br>* IV Q3W D1<br>Drug: Capecitabine<br>* PO Q3W D1-D14<br>|
| Experimental: HLX22(15mg/kg)+Trastuzumab + Chemotherapy (XELOX)<br>Participants receive 15mg/kg HLX22 IV Q3W plus trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance thereafter) IV Q3W in combination with XELOX chemotherapy | Drug: HLX22<br>* IV Q3W D1<br>Drug: Trastuzumab<br>* IV Q3W D1<br>Drug: Oxaliplatin<br>* IV Q3W D1<br>Drug: Capecitabine<br>* PO Q3W D1-D14<br>|
| Active Comparator: Placebo +Trastuzumab + Chemotherapy (XELOX)<br>Participants receive placebo IV Q3W plus trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance thereafter) IV Q3W in combination with XELOX chemotherapy | Drug: Placebo<br>* IV Q3W D1<br>Drug: Trastuzumab<br>* IV Q3W D1<br>Drug: Oxaliplatin<br>* IV Q3W D1<br>Drug: Capecitabine<br>* PO Q3W D1-D14<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) per RECIST 1.1 assessed by IRRC(Independent Radiology Review Committee) | PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 as assessed by IRRC or death due to any cause, whichever occurs first. PFS will be determined for each treatment arm | Up to 5 years | 
| Objective Response Rate (ORR) per RECIST 1.1 assessed by IRRC | ORR is defined as the percentage of participants who have a Complete Response ([CR], disappearance of all evidence of disease) or Partial Response ([PR], regression of measurable disease and no new sites) per RECIST 1.1 as assessed by IRRC. ORR will be determined for each treatment arm. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as the time from randomization to death due to any cause. OS will be determined for each treatment arm. | Up to 5 years | 
| Duration of Response (DOR) per RECIST 1.1 assessed by IRRC | For participants who demonstrate CR or PR, DOR is defined as the time from first response (CR or PR) to subsequent disease progression or death from any cause, whichever occurs first. DOR will be determined for each treatment arm | Up to 5 years | 
| Adverse Events (AE) | An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who experience an AE will be reported for each treatment arm. | Up to 5 years |