A Study to Evaluate the Efficacy and Safety of MRG003 in Patients With Advanced Gastric Cancer.

Study Overview
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Brief Summary
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The objective of this study is to assess the safety, efficacy, pharmacokinetics, and immunogenicity of MRG003 in patients with EGFR-positive, HER2-negative, inoperable locally advanced or metastatic gastric cancer.

Detailed Description
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Approximately 6054 patients will be enrolled to evaluate the safety and preliminarily efficacy of MRG003. Patients will receive 2.0 mg/kg dose of MRG003 intravenously every 3 weeks (Q3W) and may receive up to 24 months of MRG003 if there is evidence of clinical benefit to the patients.

Official Title
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A Phase II Clinical Study to Evaluate the Efficacy and Safety of MRG003 in EGFR-Positive, HER2-Negative Advanced Gastric Cancer.

Conditions
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Advanced or Metastatic Gastric Cancer, Advanced or Metastatic Gastroesophageal Junction Carcinoma

Intervention / Treatment
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* Drug: MRG003


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Willing to sign the ICF and follow the requirements specified in the protocol. Age: 18-75 years (including 18 and 75), both genders. Expected survival time≥3 months. Patients with histologically confirmed inoperable locally advanced or metastatic gastric adenocarcinoma. Tumor tissue must be EGFR positive and HER2 negative. Patients must have measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). ECOG performance score 0 or 1. Organ functions and coagulation function must meet the basic requirements. No severe cardiac dysfunction with left ventricular ejection fraction (LVEF) ≥ 50%. Serum or urine pregnancy test negative within 7 days before the first dose of investigational drug. Patients with childbearing potential must use effective contraception during the treatment and for 6 months after the last dose of treatment. Exclusion Criteria: - Squamous cell carcinoma, carcinoid, neuroendocrine carcinoma, undifferentiated carcinoma, or other gastric cancers,or adenocarcinoma with other pathological components that cannot be classified, or adenocarcin oma accompanied by other pathological components. History of hypersensitivity to any component of the study drug or to other EGFR-targeting agents. Antitumor biological therapy or immunotherapy, targeted small molecule therapy and have history of systemic chemotherapy within 4 weeks before the first administration of the investigational drug, or major surgery. Traditional Chinese medicine, Chinese patent medicine or traditional Chinese medicine formula with anti-tumor effect should not be used within 2 weeks before the first administration. Potent CYP3A4 inhibitors or inducers are in use and cannot be discontinued. Known active CNS metastasis. Uncontrolled pleural effusion, pericardial effusion or recurrent ascites. Patients with intestinal obstruction requiring treatment were excluded. Residual toxicity reactions caused by previous anti-tumor treatment or abnormal values of laboratory tests higher than grade 1 (CTCAE v5.0). Peripheral neuropathy ≥ Grade 2 (NCICTCAE version 5.0). Uncontrolled or poorly controlled hypertension. Uncontrolled or poorly controlled heart disease. Known active hepatitis B or C. Active bacterial, viral, fungal, rickettsia, or parasitic infections that require systemic anti-infective treatment. Known history of malignancy. History of ophthalmologic abnormalities History of severe skin disease Moderate to severe dyspnea at rest caused by advanced cancer or its complications, or severe primary lung disease, oxygen saturation < 93% in non-oxygen state, or history of any interstitial lung disease or interstitial lung disease (ILD) requiring oral or intravenous glucocorticoids or non-infectious pneumonia. Patients with a history of active bleeding, coagulopathy, or receiving coumarin anticoagulation therapy. History of pulmonary embolism or deep vein thrombosis within 6 months before the first administration of the investigational drug. Patients with a history of active bleeding, coagulopathy, or receiving coumarin anticoagulation therapy. Decompensated cirrhosis of Child-Pugh class B, C Complicated with severe, uncontrolled infection or known human immunodeficiency virus (HIV) infection, or diagnosed as acquired immunodeficiency syndrome (AIDS); or uncontrolled autoimmune disease; or history of allogeneic tissue/organ transplantation, stem cell or bone marrow transplantation, or solid organ transplantation. Vaccination of live virus vaccine within 30 days before the first administration of the study drug. Inactivated seasonal influenza vaccine or approved COVID-19 vaccine is allowed. Uncontrolled intercurrent illness Patients requiring parenteral nutrition within 4 weeks Women who are lactating or pregnant. Other conditions that in the clinical judgement of the investigator make the patient not suitable for participation in this 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MRG003<br>On the first day of every 3 weeks, MRG003 will be administered via intravenous infusion at 2.0 mg/kg calculated based on the actual body weight | Drug: MRG003<br>* Administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) by Independent Review Committee (IRC) | ORR is defined as the proportions of patients with a complete response (CR) and partial response (PR). ORR will be assessed by Independent Review Committee (IRC) according to RECIST v1.1. | Baseline to study completion (up to 24 months) | 
| Adverse Events (AEs) | Any reaction, side effect, or untoward event that occurs during the course of the clinical trial whether or not the event is considered related to the study drug. | Baseline to 30(for AE) and 45(for SAE) days after the last dose of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) by Investigator | ORR is defined as the proportions of patients with a complete response (CR) and partial response (PR). ORR will be assessed by investigator according to RECIST v1.1. | Baseline to study completion (up to 24 months) | 
| Progression Free Survival (PFS) | PFS is defined as the duration from the start of treatment to the onset of tumor progression or death of any cause. | Baseline to study completion (up to 24 months) | 
| Duration of Response (DoR) | DOR is defined as the duration from the initial recording of objective disease response to the first onset of tumor progression, or death of any cause. | Baseline to study completion (up to 24 months) | 
| Disease Control Rate (DCR) | DCR is defined as the proportions of patients achieving CR, PR, and stable disease (SD) after treatment. | Baseline to study completion (up to 24 months) | 
| Overall Survival (OS) | OS is defined as the duration from the start of treatment to death of any cause. | Baseline to study completion (up to 24 months) | 
| PK parameter for MRG003: (Cmax) | Maximum observed plasma concentration. | Baseline to 30 days after the last dose of study treatment | 
| PK parameter for MRG003: (AUClast) | Area under the curve up to the last validated measurable plasma concentration | Baseline to 30 days after the last dose of study treatment | 
| PK parameter for total antibody (TAb): Cmax | Maximum observed plasma concentration. | Baseline to 30 days after the last dose of study treatment | 
| PK parameter for TAb: AUClast | Area under the curve up to the last validated measurable plasma concentration | Baseline to 30 days after the last dose of study treatment | 
| PK parameter for Monomethyl Auristatin E (MMAE): Cmax | Maximum observed plasma concentration. | Baseline to 30 days after the last dose of study treatment | 
| PK parameter for MMAE: AUClast | Area under the curve up to the last validated measurable plasma concentration | Baseline to 30 days after the last dose of study treatment | 
| The proportion of patients with positive of anti-drug antibody (ADA) | The proportion of patients with positive ADA immunogenicity results. | Baseline to 30 days after the last dose of study treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRG003, Antibody Drug Conjugate (ADC), Gastric Cancer, EGFR-positive, HER2-negative