Clinical trial NCT05188209: A Study to Evaluate the Efficacy and Safety of MRG003 in Patients With Advanced Gastric Cancer.
Official title: A Phase II Clinical Study to Evaluate the Efficacy and Safety of MRG003 in EGFR-Positive, HER2-Negative Advanced Gastric Cancer.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Advanced or Metastatic Gastric Cancer
Advanced or Metastatic Gastroesophageal Junction Carcinoma
Keywords: MRG003
Antibody Drug Conjugate (ADC)
Gastric Cancer
EGFR-positive, HER2-negative
Lead sponsor: Shanghai Miracogen Inc.
Sponsor class: INDUSTRY
First posted: 2022-01-12
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate (ORR) by Independent Review Committee (IRC)
timeFrame: Baseline to study completion (up to 24 months)
measure: Adverse Events (AEs)
timeFrame: Baseline to 30(for AE) and 45(for SAE) days after the last dose of study treatment
Secondary outcomes:
measure: Objective Response Rate (ORR) by Investigator
timeFrame: Baseline to study completion (up to 24 months)
measure: Progression Free Survival (PFS)
timeFrame: Baseline to study completion (up to 24 months)
measure: Duration of Response (DoR)
timeFrame: Baseline to study completion (up to 24 months)
measure: Disease Control Rate (DCR)
timeFrame: Baseline to study completion (up to 24 months)
measure: Overall Survival (OS)
timeFrame: Baseline to study completion (up to 24 months)
measure: PK parameter for MRG003: (Cmax)
timeFrame: Baseline to 30 days after the last dose of study treatment
measure: PK parameter for MRG003: (AUClast)
timeFrame: Baseline to 30 days after the last dose of study treatment
measure: PK parameter for total antibody (TAb): Cmax
timeFrame: Baseline to 30 days after the last dose of study treatment
measure: PK parameter for TAb: AUClast
timeFrame: Baseline to 30 days after the last dose of study treatment
measure: PK parameter for Monomethyl Auristatin E (MMAE): Cmax
timeFrame: Baseline to 30 days after the last dose of study treatment
measure: PK parameter for MMAE: AUClast
timeFrame: Baseline to 30 days after the last dose of study treatment
measure: The proportion of patients with positive of anti-drug antibody (ADA)
timeFrame: Baseline to 30 days after the last dose of study treatment
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Zhengzhou
country: China
facility: Henan Tumor Hospital
state: Henan
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Aiping Zhou, Doctor
role: PRINCIPAL_INVESTIGATOR
References: