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

Phase 2

• Conditions: Advanced or Metastatic Gastroesophageal Junction Carcinoma; Advanced or Metastatic Gastric Cancer
• Interventions: Drug: MRG003

• Registration Number: NCT05188209
• Lead Sponsor: Shanghai Miracogen Inc.

Brief Summary

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

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 Timeline

• Study Start: 2021-05-24
• Status Verified: 2022-01
• Study First Submitted: 2022-01-05
• Study First Submitted QC: 2022-01-10
• Last Update Submitted: 2022-01-10
• Study First Posted: 2022-01-12
• Last Update Posted: 2022-01-12
• Primary Completion: 2023-03-21
• Study Completion: 2023-08-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MRG003	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

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) by Independent Review Committee (IRC)	Baseline to study completion (up to 24 months)	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.
Adverse Events (AEs)	Baseline to 30(for AE) and 45(for SAE) days after the last dose of study treatment	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.

Secondary Outcome Measures

Name	Time	Method
PK parameter for Monomethyl Auristatin E (MMAE): Cmax	Baseline to 30 days after the last dose of study treatment	Maximum observed plasma concentration.
Overall Survival (OS)	Baseline to study completion (up to 24 months)	OS is defined as the duration from the start of treatment to death of any cause.
Disease Control Rate (DCR)	Baseline to study completion (up to 24 months)	DCR is defined as the proportions of patients achieving CR, PR, and stable disease (SD) after treatment.
Objective Response Rate (ORR) by Investigator	Baseline to study completion (up to 24 months)	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.
Progression Free Survival (PFS)	Baseline to study completion (up to 24 months)	PFS is defined as the duration from the start of treatment to the onset of tumor progression or death of any cause.
Duration of Response (DoR)	Baseline to study completion (up to 24 months)	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.
PK parameter for MRG003: (Cmax)	Baseline to 30 days after the last dose of study treatment	Maximum observed plasma concentration.
PK parameter for MRG003: (AUClast)	Baseline to 30 days after the last dose of study treatment	Area under the curve up to the last validated measurable plasma concentration
PK parameter for total antibody (TAb): Cmax	Baseline to 30 days after the last dose of study treatment	Maximum observed plasma concentration.
PK parameter for MMAE: AUClast	Baseline to 30 days after the last dose of study treatment	Area under the curve up to the last validated measurable plasma concentration
The proportion of patients with positive of anti-drug antibody (ADA)	Baseline to 30 days after the last dose of study treatment	The proportion of patients with positive ADA immunogenicity results.
PK parameter for TAb: AUClast	Baseline to 30 days after the last dose of study treatment	Area under the curve up to the last validated measurable plasma concentration

Trial Locations

Locations (5)

Hubei Cancer Hospital; 🇨🇳 Wuhan, Hubei, China

Henan Tumor Hospital; 🇨🇳 Zhengzhou, Henan, China

Shandong Cancer Hospital; 🇨🇳 Jinan, Shandong, China

The First Affiliated Hospital of Zhengzhou University; 🇨🇳 Zhengzhou, Henan, China

Jinan Central Hospital; 🇨🇳 Jinan, Shandong, China