HX008 Plus Irinotecan Versus Placebo Plus Irinotecan as Second-line Treatment in Advanced Gastric Cancer

Study Overview
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Brief Summary
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This is a randomized, double-blinded, multicenter study to evaluate the efficacy and safety of HX008 injection combined with irinotecan versus placebo combined with irinotecan as second-line therapy in patients with adcanced gastric or gastroesophageal junction (GEJ) adenocarcinoma who have had tumor progression after first-line treatment with platinum and/or fluropyrimidine therapy.

Official Title
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A Randomized, Double-blinded, Multicenter, Phase III Clinical Study of HX008 (Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection) Plus Irinotecan Versus Placebo Plus Irinotecan as Second-line Treatment in Advanced Gastric Cancer

Conditions
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Stomach Cancer

Intervention / Treatment
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* Drug: Irinotecan Hydrochloride Injection
* Drug: HX008
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Understood and signed an informed consent form. Age ≥ 18 and ≤ 75 years old, male or female. Has histologically- or cytologically-confirmed diagnosis of locally advanced unresectable or metastatic adenocarcinoma of stomach or the esophagogastric junction (GEJ). Has experienced documented objective radiographic or clinical disease progression during or after first-line therapy containing platinum and/or fluoropyrimidine therapy. Willing to provide tissue for PD-L1 biomarker analysis. Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Score. Life expectancy ≥ 3 months. Has adequate organ function. Female participants of childbearing potential should have a negative pregnancy within 72 hours before the randomization. Male and female participants should agree to use an adequate method of contraception during the experiment and 1 year after the last administration of the test drugs. Exclusion Criteria: Has squamous cell or undifferentiated gastric cancer. Diagnosed additional maliganancy within 3 years prior to randomization with the expection of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin,curatively resected in situ cervival or non-muscle invasive bladder cancers. Has had a prior anti-cancer monoclonal antibody within 4 weeks prior to the first dose of trial treatment or who has not recovered (≤ Grade 1 or at Baseline) from AEs due to agents administered more than 4 weeks earlier. Has had prior chemotherapy,radiation therapy or targeted small molecular therapy within 2 weeks prior to the first dose of trial treatment or who has not recovered (≤ Grade 1 or at Baseline) from AEs due to a previously administrated agent. Has received prior therapy with an anti-PD-1, or anti-PD-L1, or anti-CTLA-4 agents. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Has uncontrolled ascites, pleural effusion, or pericardial effusion. Has active autoimmune disease that has required systemic treatment in past 2 years. Has received a major surgery within 4 weeks prior to randomization. Has received system treatment with corticosteroids (dose >10mg/day prednison or other therapeutic hormones) within 2 weeks prior to the first dose of trial treatment. Has incomplete intestinal obstruction, active gastrointestinal hemorrhage and perforation. Has a history of non-infectious pneumonitis that required steriods or has current pneumonitis. Has any serious and/or uncontrolled disease. Has active viral infection. Has received a live vaccine within 30 days prior to the first dose of trial treatment. Has participated in other anticancer drug clinical trials within 4 weeks. According to the judgement of the investigators, there are other factors that may lead to the termination of the study.

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: HX008 plus Irinotecan<br>Participants recieve HX008 200 mg intravenous (IV) every 3 weeks (Q3W) plus irinotecan 160 mg/m², IV, Q2W. | Drug: Irinotecan Hydrochloride Injection<br>* 160 mg/m² administered as IV infusion on Day 1 of each 14-day cycle.<br>Drug: HX008<br>* 200 mg administered as IV infusion on Day 1 of each 21-day cycle.<br>|
| Placebo Comparator: Placebo plus Irinotecan<br>Participants recieve placebo intravenous (IV) every 3 weeks (Q3W) plus irinotecan 160 mg/m², IV, Q2W. | Drug: Irinotecan Hydrochloride Injection<br>* 160 mg/m² administered as IV infusion on Day 1 of each 14-day cycle.<br>Drug: Placebo<br>* Administered as IV infusion on Day 1 of each 21-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) in All Participants | OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS is reported here for all participants in the experimental arm and placebo comparator arm. | Up to approximately 36 months | 
| Overall Survival (OS) in Participants With PD-L1 CPS≥1 | OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS is reported here for all participants in the experimental arm and placebo comparator arm with PD-L1 CPS≥1. | Up to approximately 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 assessed by investigators or death due to any cause, whichever occurs first. | Up to approximately 36 months | 
| Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | ORR was defined as the percentage of participants who have a complete response (CR) or a partial response (PR), per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by investigators. | Up to approximately 36 months | 
| Disease Control Rate (DCR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | DCR was defined as the percentage of participants who have a CR or a PR or a stable disease (SD), per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by investigators. | Up to approximately 36 months | 
| Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | DOR was defined as the time from the first documented evidence of a response of CR or PR, per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by investigators. | Up to approximately 36 months |