Clinical Trials /

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

NCT04843709

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of MRG004A in Patients With Tissue Factor Positive Advanced or Metastatic Solid Tumors
  • 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

Clinical Trial IDs

  • ORG STUDY ID: MRG004A-001
  • NCT ID: NCT04843709

Conditions

  • Advanced or Metastatic Solid Tumors

Interventions

DrugSynonymsArms
MRG004AMRG004A

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
MRG004AExperimentalAll 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).
  • MRG004A

Eligibility 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.
      
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 treatment cycle (Day 1-21)
Safety Issue:
Description: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).

Secondary Outcome Measures

Measure:Duration of Response (DoR)
Time Frame:Baseline to study completion (up to 24 months)
Safety Issue:
Description: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.
Measure:Disease Control Rate (DCR)
Time Frame:Baseline to study completion (up to 24 months)
Safety Issue:
Description:The proportion of patients who achieve CR, PR, or stable disease (SD) ≥ 6 weeks based on RECIST v1.1.
Measure:Progression Free Survival (PFS)
Time Frame:Baseline to study completion (up to 24 months)
Safety Issue:
Description:The time from the date of first study dose to disease progression or death whichever occurs first.
Measure:Overall Survive (OS)
Time Frame:Baseline to study completion (up to 24 months)
Safety Issue:
Description:The time from start of study treatment to date of death as a result of any cause.
Measure:Pharmacokinetics (PK) Parameter of MRG004A: Cmax
Time Frame:Baseline to 30 days after the last dose of study treatment
Safety Issue:
Description:Maximum observed plasma concentration.
Measure:Pharmacokinetics (PK) Parameter of MRG004A: Tmax
Time Frame:Baseline to 30 days after the last dose of study treatment
Safety Issue:
Description:Time to reach the maximum plasma concentration.
Measure:Pharmacokinetics (PK) Parameter of MRG004A: AUClast
Time Frame:Baseline to 30 days after the last dose of study treatment
Safety Issue:
Description:Area under the plasma concentration-time curve from time 0 to the time of last quantifiable concentration.
Measure:Incidence of anti-drug antibody (ADA)
Time Frame:Baseline to 30 days after the last dose of study treatment
Safety Issue:
Description:The proportion of patients with positive ADA immunogenicity results.

Details

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

Trial Keywords

  • MRG004A
  • Antibody drug conjugate (ADC)
  • Tissue factor
  • Solid tumors

Last Updated

August 11, 2021