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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04492488
Recruitment Status : Recruiting
First Posted : July 30, 2020
Last Update Posted : September 22, 2020
Sponsor:
Information provided by (Responsible Party):
Shanghai Miracogen Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Advanced or Metastatic Gastric Cancer Advanced or Metastatic Gastroesophageal Junction Cancer Drug: MRG002 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 152 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 24, 2020
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : August 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Solid Tumors
Phase 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).
Drug: MRG002
Administrated intravenously

Experimental: Locally Advanced or Metastatic Gastric/GEJ Cancer
MRG002 will be administrated by an IV infusion on Day 1 of every 3 weeks (21-day cycle).
Drug: MRG002
Administrated intravenously




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: DLT will be evaluated during the first 21-day treatment cycle (Cycle 1) ]
    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.

  2. Recommended Phase II Dose (RP2D) [ Time Frame: Day 1 to Day 21 of Cycle 1 ]
    Identify the recommended Phase II dose (RP2D) of MRG002 for Phase II clinical study. The RP2D may be the same as the MTD or an evaluable dose level lower than the MTD.

  3. Objective Response Rate (ORR) [ Time Frame: Baseline to study completion (24 months) ]
    Objective response rate (ORR) will be assessed by Independent Central Review (ICR) based on RECIST v1.1. Cumulative safety and dosing data will be reviewed by an independent Data Safety Monitoring Board (DSMB).

  4. Incidence of Adverse Events (AEs) [ Time Frame: After signing informed consent until 45 days after the last dose of MRG002 ]
    AEs will be coded using MedDAR. Descriptive statistics will be used to summarize results to assess the safety and tolerability profile of MRG002.


Secondary Outcome Measures :
  1. Duration of Response (DoR) [ Time Frame: Baseline to study completion (24 months) ]
    Sensitivity analyses of DoR from the Investigator's assessment will be performed in the final analysis.

  2. Disease Control Rate (DCR) [ Time Frame: Baseline to study completion (24 months) ]
    Sensitivity analyses of DCR from the Investigator's assessment will be performed in the final analysis.

  3. Progression Free Survival (PFS) [ Time Frame: Baseline to study completion (24 months) ]
    Sensitivity analyses of PFS from the Investigator's assessment will be performed in the final analysis.

  4. Pharmacokinetics (PK) parameter for MRG002: Maximum Drug Concentration (Cmax) [ Time Frame: Baseline to study completion (24 months) ]
    Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics.

  5. 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) ]
    AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statistics.

  6. PK parameter for total antibody (TAb): Cmax [ Time Frame: Baseline to study completion (24 months) ]
    Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics.

  7. PK parameter for TAb: AUClast [ Time Frame: Baseline to study completion (24 months) ]
    AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statistics.

  8. PK parameter for Monomethyl Auristatin E (MMAE): Cmax [ Time Frame: Baseline to study completion (24 months) ]
    Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics.

  9. PK parameter for MMAE: AUClast [ Time Frame: Baseline to study completion (24 months) ]
    AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statistics.

  10. Immunogenicity [ Time Frame: Baseline to study completion (24 months) ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04492488


Contacts
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Contact: Tiger Bee, MBA, MA, MS 267-317-0699 clinicaltrials@miracogen.com.cn
Contact: Sally Fisher, RN, BSN 813-395-4638 sally.fisher@wuxiapptec.com

Locations
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United States, Ohio
Gabrail Cancer Center Research Recruiting
Canton, Ohio, United States, 44718
Contact: Nashat Gabrail, MD    330-492-3345    ngabrailmd@gabrailcancercenter.com   
Sponsors and Collaborators
Shanghai Miracogen Inc.
Investigators
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Principal Investigator: Crystal Denlinger, MD Fox Chase Cancer Center
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Responsible Party: Shanghai Miracogen Inc.
ClinicalTrials.gov Identifier: NCT04492488    
Other Study ID Numbers: MRG002-101
First Posted: July 30, 2020    Key Record Dates
Last Update Posted: September 22, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Shanghai Miracogen Inc.:
MRG002
Antibody Drug Conjugate (ADC)
HER2
Solid tumors
Gastric/GEJ Cancer
Additional relevant MeSH terms:
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Neoplasms