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A Study of MRG004A in Patients With Tissue Factor Positive Advanced or Metastatic Solid Tumors

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: NCT04843709
Recruitment Status : Recruiting
First Posted : April 13, 2021
Last Update Posted : May 26, 2022
Sponsor:
Information provided by (Responsible Party):
Shanghai Miracogen Inc.

Brief Summary:
The objective of this study is to evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of MRG004A in patients with Tissue Factor positive advanced or metastatic solid tumors.

Condition or disease Intervention/treatment Phase
Advanced or Metastatic Solid Tumors Drug: MRG004A Phase 1 Phase 2

Detailed Description:
This study consists of two parts. Part A is a dose escalation study to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of MRG004A. Part B is a disease specific multi-cohort dose expansion study to further assess the efficacy and safety of MRG004A at confirmed RP2D.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 181 participants
Allocation: N/A
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, Tolerability, Anti-Tumor Activity and Pharmacokinetics of MRG004A in Patients With Tissue Factor Positive Advanced or Metastatic Solid Tumors
Actual Study Start Date : July 26, 2021
Estimated Primary Completion Date : April 2024
Estimated Study Completion Date : June 2025

Arm Intervention/treatment
Experimental: MRG004A
All patients in Part A (dose escalation) and Part B (dose expansion) will be administrated MRG004A on Day 1 of every 3 weeks (21-day cycle).
Drug: MRG004A
Administrated intravenously




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: DLT will be evaluated during the first treatment cycle (Day 1-21) ]
    The highest dose confirmed wherein less than 2 out of 6, or < 33% of evaluable patients in a treatment cohort experiences dose-limiting toxicity (DLT).

  2. Recommended Phase II Dose (RP2D) [ Time Frame: Baseline to study completion (up to 24 months) ]
    The dose level of MRG004A recommended for further clinical studies based on assessment of the safety, efficacy and PK data from Part A of this study.

  3. Objective Response Rate (ORR) [ Time Frame: Baseline to study completion (up to 24 months) ]
    The proportion of patients who achieve complete response (CR) or partial response (PR) as assessed by the Independent Central Review (ICR).

  4. Adverse Events (AEs) [ Time Frame: From signing informed consent until 45 days after the last dose of MRG004A ]
    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 :
  1. Duration of Response (DoR) [ Time Frame: Baseline to study completion (up to 24 months) ]
    The time interval between the date of the earliest qualifying response and the date of disease progression or death for any cause, whichever occurs earlier.

  2. Disease Control Rate (DCR) [ Time Frame: Baseline to study completion (up to 24 months) ]
    The proportion of patients who achieve CR, PR, or stable disease (SD) ≥ 6 weeks based on RECIST v1.1.

  3. Progression Free Survival (PFS) [ Time Frame: Baseline to study completion (up to 24 months) ]
    The time from the date of first study dose to disease progression or death whichever occurs first.

  4. Overall Survive (OS) [ Time Frame: Baseline to study completion (up to 24 months) ]
    The time from start of study treatment to date of death as a result of any cause.

  5. Pharmacokinetics (PK) Parameter of MRG004A: Cmax [ Time Frame: Baseline to 30 days after the last dose of study treatment ]
    Maximum observed plasma concentration.

  6. Pharmacokinetics (PK) Parameter of MRG004A: Tmax [ Time Frame: Baseline to 30 days after the last dose of study treatment ]
    Time to reach the maximum plasma concentration.

  7. Pharmacokinetics (PK) Parameter of MRG004A: AUClast [ Time Frame: Baseline to 30 days after the last dose of study treatment ]
    Area under the plasma concentration-time curve from time 0 to the time of last quantifiable concentration.

  8. Incidence of anti-drug antibody (ADA) [ Time Frame: Baseline to 30 days after the last dose of study treatment ]
    The proportion of patients with positive ADA immunogenicity results.



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:

  1. Understands and provides written informed consent and willing to follow the requirements specified in protocol.
  2. Age ≥18 years.
  3. Life expectancy ≥6 months.
  4. For Part B patients, documented Tissue Factor (TF) presence in tumor biopsy specimens obtained from archival or re-biopsy specimens by immunohistochemistry (IHC) protein expression.
  5. Must have histologically or cytologically confirmed unresectable or metastatic cancer with documented disease progression during prior therapy, or relapse or progression following approved standard therapy for their tumor types- Part A and Part B.
  6. Part B: Patients who have documented progression during or relapse following standard therapy, no further treatment options that are known to improve survival, and participation in a clinical trial is a reasonable therapeutic option.
  7. Patients must have measurable disease per RECIST v1.1.
  8. ECOG performance status of 0 or 1.
  9. Acceptable bone marrow, hepatic, cardiac, renal, and coagulation function.
  10. A negative serum pregnancy test if female and aged between 18-55 years old.
  11. Patients, both females and males, of reproductive potential must agree to use adequate contraception during and for 180 days after the last infusion of MRG004A.

Exclusion Criteria:

  1. Archival or biopsy tumor shows TF IHC membrane or cytosolic score of zero, no TF-positive expression or no TF-positive staining in Part B patients.
  2. Toxicities (except alopecia & fatigue) due to prior antitumor therapy are greater than CTCAE v5.0 Grade 1.
  3. Toxicities due to prior radiotherapy that have not resolved to Grade ≤ 1 CTCAE v5.0 at least 21 days prior to the first treatment.
  4. Untreated, unstable or uncontrolled central nervous system (CNS) metastases.
  5. Any other type of anti-cancer therapy within 21 days of the first dose of study treatment. Use of any other type of anti-cancer treatment is prohibited throughout the study.
  6. Patients with increased bleeding risk.
  7. Presence of severe cardiac dysfunction.
  8. Pulmonary embolism or deep vein thrombosis within 3 months prior to the first dose of study drug.
  9. Concurrent malignancy within 5 years prior to entry.
  10. Uncontrolled or poorly controlled hypertension.
  11. History of ventricular tachycardia, or torsade des pointes.
  12. History of moderate to severe dyspnea at rest.
  13. 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.
  14. Known allergic reactions to any component or excipient of MRG004A or known allergic reactions to other prior anti-TF (including investigational) or other monoclonal antibody ≥ Grade 3.
  15. 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.
  16. Active uncontrolled bacterial, viral, fungal, rickettsial, or parasitic infection.
  17. Use of systemic corticosteroids within 4 weeks prior to the first dose of treatment.
  18. Use of strong CYP3A4 inhibitors or inducers with MRG004A.
  19. Other excluded medications or treatment: therapeutic anti-coagulative, or long-term anti-platelet treatment; multivitamins, calcium, vitamin D, and prophylactic anti-RANKL (denosumab) and zoledronic acid therapies for bone metastases are allowed.
  20. Any patient with a positive pregnancy or is breast-feeding.
  21. 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.

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): NCT04843709


Contacts
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Contact: Jenny Li 650-237-9339 clinicaltrials@miracogen.com.cn
Contact: Leanne Drummond, Bachelor 984-208-9519 leanne.drummond@worldwide.com

Locations
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United States, California
Chao Family Comprehensive Cancer Center Recruiting
Orange, California, United States, 92868-3201
Contact: Carmen Lu       ucstudy@hs.uci.edu   
United States, New York
Memorial Sloan Kettering 60th Street Outpatient Center Recruiting
New York, New York, United States, 10065
Contact: Amin Yaqubie       yaqubiea@mskcc.org   
United States, Ohio
Gabrail Cancer Center Research Recruiting
Canton, Ohio, United States, 44718
Contact: Nashat Y Gabrail, MD    330-492-3345    ngabrailmd@gabrailcancercenter.com   
Contact: Carrie Smith    330-492-3345 ext 208    csmith@gabrailcancercenter.com   
The Christ Hospital Cancer Center Recruiting
Cincinnati, Ohio, United States, 45219
Contact: Abby Reed       abby.reed@thechristhospital.com   
United States, Pennsylvania
Gettysburg Cancer Center Recruiting
Gettysburg, Pennsylvania, United States, 17325
Contact: Christine Nocera       christine@gettysburgoncology.com   
United States, Virginia
Virginia Cancer Specialists Recruiting
Fairfax, Virginia, United States, 22031
Contact: Marcy Sullivan, RN, BSN, OCN    703-208-9268    Marcy.Sullivan@usoncology.com   
Sponsors and Collaborators
Shanghai Miracogen Inc.
Investigators
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Principal Investigator: Nashat Y Gabrail, MD Gabrail Cancer Center Research
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Responsible Party: Shanghai Miracogen Inc.
ClinicalTrials.gov Identifier: NCT04843709    
Other Study ID Numbers: MRG004A-001
First Posted: April 13, 2021    Key Record Dates
Last Update Posted: May 26, 2022
Last Verified: August 2021
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.:
MRG004A
Antibody drug conjugate (ADC)
Tissue factor
Solid tumors
Additional relevant MeSH terms:
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Neoplasms