Ph1b/2 Study of the Safety and Efficacy of SHR-A1811 Combinations in Advanced HER2+ Gastric Cancer

Study Overview
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Brief Summary
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This is an open,multicentre phase Ib/II study. The purpose of phase Ib is to evaluated the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary antitumor activity of SHR-A1811 in combination with chemotherapy and/or immunotherapy in HER2-positive advanced/metastatic gastric/gastroesophageal junction adenocarcinoma patients. The Phase II study was designed to evaluate the efficacy and safety of SHR-A1811 in combination with chemotherapy and/or immunotherapy for advanced/metastatic HER2-positive gastric/gastroesophageal conjunctional adenocarcinoma patients.

Official Title
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A Phase Ib/II Study of SHR-A1811 Combinations in Patients With Advanced/Metastatic HER2+ Gastric /Gastroesophageal Junction Adenocarcinoma

Conditions
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HER2+ Gastric Cancer/Gastroesophageal Junction Adenocarcinoma

Intervention / Treatment
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* Drug: SHR-A1811；SHR-1701；capecitabine；oxaliplatin
* Drug: SHR-A1811；SHR-1701；capecitabine；oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age from 18 to 75 , Male and female participants Local advanced unresectable or metastatic disease Pathologically documented adenocarcinoma of gastric or gastroesophageal junction; HER2 positive; Phase Ib: progression at least one prior Regimen or could not tolerate the standard treatment，pevious anti-HER2 therapy was included Phase II: previously untreated patients ; ECOG 0-1; The expected survival ≥3 months; Sufficient bone marrow and organ functions; Exclusion Criteria: There were ascites, pleural effusion and pericardial effusion that needed to be treated; Major surgery was performed within 4 weeks; Have active autoimmune disease or history of autoimmune disease; Patients with interstitial pneumonia; There was severe infection within 4 weeks before starting the study treatment; Patients with active pulmonary tuberculosis infection history within 1 year before enrollment; Serious cardiovascular and cerebrovascular diseases; Gastrointestinal perforation and/or gastrointestinal fistula occurred within 6 months before enrollment;

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1A: SHR-A1811 and SHR-1701<br> | Drug: SHR-A1811；SHR-1701；capecitabine；oxaliplatin<br>* (Arm 1A) Drug: SHR-A1811,administered as an IV infusion Drug: SHR-1701, administered as an IV infusion; (Arm 1B) Drug: SHR-A1811,administered as an IV infusion Drug：capecitabine, administered orally； (Arm 1C) Drug: SHR-A1811,administered as an IV infusion Drug: SHR-1701, administered as an IV infusion Drug：capecitabine, administered orally； (Arm 1D) Drug: SHR-A1811,administered as an IV infusion Drug：capecitabine, administered orally； Drug：oxaliplatin，administered as an IV infusion<br>|
| Experimental: Arm 1B: SHR-A1811 and capecitabine<br> | Drug: SHR-A1811；SHR-1701；capecitabine；oxaliplatin<br>* (Arm 1A) Drug: SHR-A1811,administered as an IV infusion Drug: SHR-1701, administered as an IV infusion; (Arm 1B) Drug: SHR-A1811,administered as an IV infusion Drug：capecitabine, administered orally； (Arm 1C) Drug: SHR-A1811,administered as an IV infusion Drug: SHR-1701, administered as an IV infusion Drug：capecitabine, administered orally； (Arm 1D) Drug: SHR-A1811,administered as an IV infusion Drug：capecitabine, administered orally； Drug：oxaliplatin，administered as an IV infusion<br>|
| Experimental: Arm 1C: SHR-A181,SHR-1701,and capecitabine<br> | Drug: SHR-A1811；SHR-1701；capecitabine；oxaliplatin<br>* (Arm 1A) Drug: SHR-A1811,administered as an IV infusion Drug: SHR-1701, administered as an IV infusion; (Arm 1B) Drug: SHR-A1811,administered as an IV infusion Drug：capecitabine, administered orally； (Arm 1C) Drug: SHR-A1811,administered as an IV infusion Drug: SHR-1701, administered as an IV infusion Drug：capecitabine, administered orally； (Arm 1D) Drug: SHR-A1811,administered as an IV infusion Drug：capecitabine, administered orally； Drug：oxaliplatin，administered as an IV infusion<br>|
| Experimental: Arm 1D: SHR-A1811,capecitabine,and oxaliplatin<br> | Drug: SHR-A1811；SHR-1701；capecitabine；oxaliplatin<br>* (Arm 1A) Drug: SHR-A1811,administered as an IV infusion Drug: SHR-1701, administered as an IV infusion; (Arm 1B) Drug: SHR-A1811,administered as an IV infusion Drug：capecitabine, administered orally； (Arm 1C) Drug: SHR-A1811,administered as an IV infusion Drug: SHR-1701, administered as an IV infusion Drug：capecitabine, administered orally； (Arm 1D) Drug: SHR-A1811,administered as an IV infusion Drug：capecitabine, administered orally； Drug：oxaliplatin，administered as an IV infusion<br>|
| Experimental: Arm 2A: SHR-A1811 and SHR-1701<br> | Drug: SHR-A1811；SHR-1701；capecitabine；oxaliplatin<br>* (Arm 2A) Drug: SHR-A1811,administered as an IV infusion Drug: SHR-1701, administered as an IV infusion; (Arm 2B) Drug: SHR-A1811,administered as an IV infusion Drug: SHR-1701, administered as an IV infusion Drug：capecitabine, administered orally； (Arm 2C) Drug: SHR-A1811,administered as an IV infusion Drug：capecitabine, administered orally； Drug：oxaliplatin，administered as an IV infusion<br>|
| Experimental: Arm 2B: SHR-A181,SHR-1701,and capecitabine<br> | Drug: SHR-A1811；SHR-1701；capecitabine；oxaliplatin<br>* (Arm 2A) Drug: SHR-A1811,administered as an IV infusion Drug: SHR-1701, administered as an IV infusion; (Arm 2B) Drug: SHR-A1811,administered as an IV infusion Drug: SHR-1701, administered as an IV infusion Drug：capecitabine, administered orally； (Arm 2C) Drug: SHR-A1811,administered as an IV infusion Drug：capecitabine, administered orally； Drug：oxaliplatin，administered as an IV infusion<br>|
| Experimental: Arm 2C: SHR-A1811,capecitabine,and oxaliplatin<br> | Drug: SHR-A1811；SHR-1701；capecitabine；oxaliplatin<br>* (Arm 2A) Drug: SHR-A1811,administered as an IV infusion Drug: SHR-1701, administered as an IV infusion; (Arm 2B) Drug: SHR-A1811,administered as an IV infusion Drug: SHR-1701, administered as an IV infusion Drug：capecitabine, administered orally； (Arm 2C) Drug: SHR-A1811,administered as an IV infusion Drug：capecitabine, administered orally； Drug：oxaliplatin，administered as an IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase Ib: Dose limiting toxicity (DLT) rates, Occurrence of adverse events (AEs), and serious adverse events (SAEs) |  | Safety will be assessed for approximately 24 months from informed consent | 
| Phase II: Objective Response Rate (ORR)[ |  | An average of approximately 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR（Phase Ib） |  | An average of approximately 12 months | 
| DoR（Phase Ib） |  | An average of approximately 18 months | 
| PFS（Phase Ib） |  | An average of approximately 18 months | 
| OS（Phase Ib） |  | An average of approximately 30 months | 
| DoR（Phase II） |  | An average of approximately 18 months | 
| PFS（Phase II） |  | An average of approximately 18 months | 
| OS（Phase II） |  | An average of approximately 30 months | 
| Occurrence of adverse events (AEs), and serious adverse events (SAEs) （Phase II） |  | Safety will be assessed for approximately 24 months from informed consent] |