A Phase II Clinical Study to Evaluate the Efficacy and Safety of MRG003 in EGFR-Positive, HER2-Negative Advanced Gastric Cancer.
Overview
- Phase
- Phase 2
- Intervention
- MRG003
- Conditions
- Advanced or Metastatic Gastric Cancer
- Sponsor
- Shanghai Miracogen Inc.
- Enrollment
- 60
- Locations
- 5
- Primary Endpoint
- Objective Response Rate (ORR) by Independent Review Committee (IRC)
- Last Updated
- 4 years ago
Overview
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.
Investigators
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
- •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.
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.
Arms & Interventions
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
Intervention: MRG003
Outcomes
Primary Outcomes
Objective Response Rate (ORR) by Independent Review Committee (IRC)
Time Frame: 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)
Time Frame: 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 Outcomes
- PK parameter for Monomethyl Auristatin E (MMAE): Cmax(Baseline to 30 days after the last dose of study treatment)
- Overall Survival (OS)(Baseline to study completion (up to 24 months))
- Disease Control Rate (DCR)(Baseline to study completion (up to 24 months))
- Objective Response Rate (ORR) by Investigator(Baseline to study completion (up to 24 months))
- Progression Free Survival (PFS)(Baseline to study completion (up to 24 months))
- Duration of Response (DoR)(Baseline to study completion (up to 24 months))
- PK parameter for MRG003: (Cmax)(Baseline to 30 days after the last dose of study treatment)
- PK parameter for MRG003: (AUClast)(Baseline to 30 days after the last dose of study treatment)
- PK parameter for total antibody (TAb): Cmax(Baseline to 30 days after the last dose of study treatment)
- PK parameter for MMAE: AUClast(Baseline to 30 days after the last dose of study treatment)
- The proportion of patients with positive of anti-drug antibody (ADA)(Baseline to 30 days after the last dose of study treatment)
- PK parameter for TAb: AUClast(Baseline to 30 days after the last dose of study treatment)