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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced or Metastatic Gastric Cancer; Advanced or Metastatic Gastroesophageal Junction Carcinoma
• Intervention / Treatment: Drug: MRG003

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450052
      • Recruiting
      • The First Affiliated Hospital of Zhengzhou University
      • Contact: Wenhua Xue, Secretary; Phone Number: 0371-66295624; Email: ZDYFYgcp@163.com
      • Principal Investigator: Qingxia Fan, Doctor
    • Zhengzhou, Henan, China
      • Recruiting
      • Henan Tumor Hospital
      • Contact: Baoxia He, Director; Phone Number: 0371-65588007 0371-65588007; Email: hnszlyygcp@163.com
      • Principal Investigator: Ying Liu, Doctor
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Recruiting
      • Hubei Cancer Hospital
      • Contact: Fang Xu, Secretary; Phone Number: 027-87670003 027-87670003; Email: xdm126@126.com
      • Principal Investigator: Xinjun Liang, Doctor
  • Shandong
    • Jinan, Shandong, China, 250117
      • Recruiting
      • Shandong Cancer Hospital
      • Contact: Zhehai Wang, Secretary; Phone Number: 0531-67626073; Email: ywb234@126.com
      • Principal Investigator: Changzheng Li, Doctor
    • Jinan, Shandong, China, 250013
      • Recruiting
      • Jinan Central Hospital
      • Contact: Xiaoran Zhang, Secretary; Phone Number: 0531-86970712; Email: zxyyywsy@163.com
      • Principal Investigator: Meili Sun, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MRG003; 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; Administered intravenously

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shanghai Miracogen Inc.
• Investigators: Principal Investigator: Aiping Zhou, Doctor, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2021
• Primary Completion (Anticipated): March 21, 2023
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: January 5, 2022
• First Submitted That Met QC Criteria: January 10, 2022
• First Posted (Actual): January 12, 2022

Study Record Updates

• Last Update Posted (Actual): January 12, 2022
• Last Update Submitted That Met QC Criteria: January 10, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Gastric Cancer; Antibody Drug Conjugate (ADC); MRG003; EGFR-positive, HER2-negative
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: MRG003-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No