Clinical Trials /

A Study of MRG002 in Patients With HER2-Positive Advanced Solid Tumors and Locally Advanced or Metastatic Gastric/Gastroesophageal Junction (GEJ) Cancer

NCT04492488

Description:

The objective of this study is to assess the safety, efficacy, and pharmacokinetics of MRG002, as well as the immunogenicity as defined by the incidence of anti-drug antibody (ADA) of MRG002 in patients with HER2-positive advanced solid tumors and locally advanced or metastatic gastric/gastroesophageal junction (GEJ) cancer.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of MRG002 in Patients With HER2-Positive Advanced Solid Tumors and Locally Advanced or Metastatic Gastric/Gastroesophageal Junction (GEJ) Cancer
  • Official Title: An Open-Label, Multi-center Phase I/II Dose Escalation and Expansion Study to Assess the Safety, Efficacy and Pharmacokinetics of MRG002 in Patients With HER2-Positive Advanced Solid Tumors and Locally Advanced or Metastatic Gastric/Gastroesophageal Junction (GEJ) Cancer

Clinical Trial IDs

  • ORG STUDY ID: MRG002-101
  • NCT ID: NCT04492488

Conditions

  • Advanced Solid Tumors
  • Advanced or Metastatic Gastric Cancer
  • Advanced or Metastatic Gastroesophageal Junction Cancer

Interventions

DrugSynonymsArms
MRG002Locally Advanced or Metastatic Gastric/GEJ Cancer

Purpose

The objective of this study is to assess the safety, efficacy, and pharmacokinetics of MRG002, as well as the immunogenicity as defined by the incidence of anti-drug antibody (ADA) of MRG002 in patients with HER2-positive advanced solid tumors and locally advanced or metastatic gastric/gastroesophageal junction (GEJ) cancer.

Detailed Description

      This study consists of two parts. In Part A, patients will receive MRG002 as a monotherapy at
      doses of 2.2, 2.6, or 3.0 mg/kg intravenously (IV) over 60-90 minute on Day 1 of every 3
      weeks (Q3W), to determine the maximum tolerated dose (MTD) and recommended phase II dose
      (RP2D). In part B, patients will receive a single IV infusion of MRG002 at RP2D on Day 1 of
      Q3W.
    

Trial Arms

NameTypeDescriptionInterventions
Solid TumorsExperimentalPhase I Dose Escalation: MRG002 will be administrated by an IV infusion of escalating doses (starting dose of 2.2 mg/kg, followed by 2.6 mg/kg, 3.0 mg/kg) on Day 1 of every 3 weeks (21-day cycle).
  • MRG002
Locally Advanced or Metastatic Gastric/GEJ CancerExperimentalMRG002 will be administrated by an IV infusion on Day 1 of every 3 weeks (21-day cycle).
  • MRG002

Eligibility Criteria

        Inclusion Criteria:

          -  The patient must be able to provide written informed consent and follow the
             requirements specified in protocol.

          -  Age: ≥18 years.

          -  Life expectancy ≥6 months.

          -  Must have histologically or cytologically confirmed HER2-positive metastatic,
             unresectable cancer and must have had prior disease progression on all standard
             therapies for their tumor.

          -  Available archival tumor tissue (archival or from a new biopsy).

          -  At least one non-irradiated measurable tumor lesion according to RECIST v1.1.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          -  Acceptable liver, renal, hematologic and coagulation function.

        Exclusion Criteria:

          -  Toxicities (except alopecia & fatigue) due to prior antitumor therapy are higher than
             CTCAE v5.0 Grade 1.

          -  Toxicities due to radiotherapy (higher than grade 1) have not resolved to CTCAE v5.0
             Grade ≤1 at least 21 days prior to the screening visit.

          -  Prior palliative or therapeutic radiation therapy to any RECIST v1.1 target lesion
             that defines baseline measurable disease for the study.

          -  Untreated or uncontrolled central nervous system (CNS) metastases.

          -  Any chemotherapy, biotherapy, immunotherapy, radiotherapy or other anti-tumor therapy
             within 3 weeks of the first dose of study treatment.

          -  Any severe cardiac dysfunction within 6 months of enrollment.

          -  Pulmonary embolism or deep vein thrombosis within 3 months prior to the first dose of
             study drug.

          -  Concurrent malignancy within 5 years prior to entry.

          -  Uncontrolled hypertension (systolic blood pressure >160 mmHg or diastolic blood
             pressure > 100 mmHg).

          -  History of ventricular tachycardia, or torsade des pointes.

          -  History of moderate to severe dyspnea at rest due to advanced malignancies or their
             complications, severe primary lung disease, current need of continuous oxygen therapy,
             or clinically active interstitial lung disease (ILD) or pneumonitis.

          -  Major surgery within 4 weeks of the first dose of study treatment and not fully
             recovered. Minor surgery within 2 weeks prior to study treatment.

          -  Known allergic reactions to any component or excipient of MRG002 or known allergic
             reactions to trastuzumab or other prior anti-HER2 or other monoclonal antibody ≥ Grade
             3.

          -  Patients who have any known liver disease, including chronic hepatitis B, hepatitis C,
             autoimmune hepatic disorders, primary biliary cirrhosis or sclerosing cholangitis;
             Patients who have concurrent, serious, uncontrolled infections or known infection with
             HIV, or have a diagnosed acquired immunodeficiency syndrome (AIDS); or an uncontrolled
             autoimmune disease, or have undergone organ transplant.

          -  Active uncontrolled bacterial, viral, fungal, rickettsial, or parasitic infection.

          -  Any severe and/or uncontrolled systemic disease that at the discretion of investigator
             and sponsor makes it undesirable for the patient to participate in this study.

          -  Use of systemic corticosteroids within 4 weeks prior to the first dose of treatment.

          -  Use of strong CYP3A4 inhibitors.

          -  Pregnancy or breast-feeding.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD)
Time Frame:DLT will be evaluated during the first 21-day treatment cycle (Cycle 1)
Safety Issue:
Description:The dose level in which (i) less than 2 out of 6 patients in a treatment cohort experiences dose-limiting toxicity (DLT); or (ii) <33% of an evaluable patient treatment cohort experiences DLT.

Secondary Outcome Measures

Measure:Duration of Response (DoR)
Time Frame:Baseline to study completion (24 months)
Safety Issue:
Description:Sensitivity analyses of DoR from the Investigator's assessment will be performed in the final analysis.
Measure:Disease Control Rate (DCR)
Time Frame:Baseline to study completion (24 months)
Safety Issue:
Description:Sensitivity analyses of DCR from the Investigator's assessment will be performed in the final analysis.
Measure:Progression Free Survival (PFS)
Time Frame:Baseline to study completion (24 months)
Safety Issue:
Description:Sensitivity analyses of PFS from the Investigator's assessment will be performed in the final analysis.
Measure:Pharmacokinetics (PK) parameter for MRG002: Maximum Drug Concentration (Cmax)
Time Frame:Baseline to study completion (24 months)
Safety Issue:
Description:Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics.
Measure:PK parameter for MRG002: Area Under the Curve Up to the Last Validated Measurable Plasma Concentration (AUClast)
Time Frame:Baseline to study completion (24 months)
Safety Issue:
Description:AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statistics.
Measure:PK parameter for total antibody (TAb): Cmax
Time Frame:Baseline to study completion (24 months)
Safety Issue:
Description:Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics.
Measure:PK parameter for TAb: AUClast
Time Frame:Baseline to study completion (24 months)
Safety Issue:
Description:AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statistics.
Measure:PK parameter for Monomethyl Auristatin E (MMAE): Cmax
Time Frame:Baseline to study completion (24 months)
Safety Issue:
Description:Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics.
Measure:PK parameter for MMAE: AUClast
Time Frame:Baseline to study completion (24 months)
Safety Issue:
Description:AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statistics.
Measure:Immunogenicity
Time Frame:Baseline to study completion (24 months)
Safety Issue:
Description:5 mL Blood samples for anti-drug antibody (ADA) analysis will be collected each time according to the pre-defined timepoints. The incidence of ADA will be summarized for all patients who received at least one administration of MRG002.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Shanghai Miracogen Inc.

Trial Keywords

  • MRG002
  • Antibody Drug Conjugate (ADC)
  • HER2
  • Solid tumors
  • Gastric/GEJ Cancer

Last Updated

July 27, 2020