- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04843709
A Study of MRG004A in Patients With Tissue Factor Positive Advanced or Metastatic Solid Tumors
September 6, 2022 updated by: Shanghai Miracogen Inc.
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
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.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Anticipated)
181
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Jenny Li
- Phone Number: 650-237-9339
- Email: clinicaltrials@miracogen.com.cn
Study Contact Backup
- Name: Leanne Drummond, Bachelor
- Phone Number: 984-208-9519
- Email: leanne.drummond@worldwide.com
Study Locations
-
-
Hunan
-
Changsha, Hunan, China, 410013
- Not yet recruiting
- Hunan Cancer Hospital
-
Contact:
- Jie Tang, M.D.
- Phone Number: 86-15274836636
- Email: tangjie@hnca.org.cn
-
-
Shanghai
-
Shanghai, Shanghai, China, 201321
- Not yet recruiting
- Fudan University Shanghai Cancer Center
-
Contact:
- Jian Zhang, M.D
- Phone Number: 86-18017312991
- Email: Syner2000@163.com
-
Contact:
- Xiaohua Wu, M.D
- Phone Number: 81006 86-21-64175590
- Email: wu.xh@fudan.edu.cn
-
-
Zhejiang
-
Hangzhou, Zhejiang, China, 310003
- Not yet recruiting
- The First Affiliated Hospital, College of Medicine, Zhejiang University
-
Contact:
- Jianzhen Shan, M.D.
- Phone Number: 86-13757128607
- Email: jianzhenshan@163.com
-
-
-
-
California
-
Orange, California, United States, 92868-3201
- Recruiting
- Chao Family Comprehensive Cancer Center
-
Contact:
- Carmen Lu
- Email: ucstudy@hs.uci.edu
-
-
New York
-
New York, New York, United States, 10065
- Recruiting
- Memorial Sloan Kettering 60th Street Outpatient Center
-
Contact:
- Amin Yaqubie
- Email: yaqubiea@mskcc.org
-
-
Ohio
-
Canton, Ohio, United States, 44718
- Recruiting
- Gabrail Cancer Center Research
-
Contact:
- Nashat Y Gabrail, MD
- Phone Number: 330-492-3345
- Email: ngabrailmd@gabrailcancercenter.com
-
Contact:
- Carrie Smith
- Phone Number: 208 330-492-3345
- Email: csmith@gabrailcancercenter.com
-
Cincinnati, Ohio, United States, 45219
- Recruiting
- The Christ Hospital Cancer Center
-
Contact:
- Abby Reed
- Email: abby.reed@thechristhospital.com
-
-
Pennsylvania
-
Gettysburg, Pennsylvania, United States, 17325
- Recruiting
- Gettysburg Cancer Center
-
Contact:
- Christine Nocera
- Email: christine@gettysburgoncology.com
-
-
Virginia
-
Fairfax, Virginia, United States, 22031
- Recruiting
- Virginia Cancer Specialists
-
Contact:
- Marcy Sullivan, RN, BSN, OCN
- Phone Number: 703-208-9268
- Email: Marcy.Sullivan@usoncology.com
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Understands and provides written informed consent and willing to follow the requirements specified in protocol.
- Age ≥18 years.
- Life expectancy ≥6 months.
- 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.
- 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.
- 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.
- Patients must have measurable disease per RECIST v1.1.
- ECOG performance status of 0 or 1.
- Acceptable bone marrow, hepatic, cardiac, renal, and coagulation function.
- A negative serum pregnancy test if female and aged between 18-55 years old.
- 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:
- 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.
- Toxicities (except alopecia & fatigue) due to prior antitumor therapy are greater than CTCAE v5.0 Grade 1.
- Toxicities due to prior radiotherapy that have not resolved to Grade ≤ 1 CTCAE v5.0 at least 21 days prior to the first treatment.
- Untreated, unstable or uncontrolled central nervous system (CNS) metastases.
- 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.
- Patients with increased bleeding risk.
- Presence of severe cardiac dysfunction.
- 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 or poorly controlled hypertension.
- History of ventricular tachycardia, or torsade des pointes.
- History of moderate to severe dyspnea at rest.
- 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 MRG004A or known allergic reactions to other prior anti-TF (including investigational) 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.
- Use of systemic corticosteroids within 4 weeks prior to the first dose of treatment.
- Use of strong CYP3A4 inhibitors or inducers with MRG004A.
- 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.
- Any patient with a positive pregnancy or is breast-feeding.
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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).
|
Administrated intravenously
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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).
|
DLT will be evaluated during the first treatment cycle (Day 1-21)
|
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.
|
Baseline to study completion (up to 24 months)
|
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).
|
Baseline to study completion (up to 24 months)
|
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.
|
From signing informed consent until 45 days after the last dose of MRG004A
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Baseline to study completion (up to 24 months)
|
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.
|
Baseline to study completion (up to 24 months)
|
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.
|
Baseline to study completion (up to 24 months)
|
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.
|
Baseline to study completion (up to 24 months)
|
Pharmacokinetics (PK) Parameter of MRG004A: Cmax
Time Frame: Baseline to 30 days after the last dose of study treatment
|
Maximum observed plasma concentration.
|
Baseline to 30 days after the last dose of study treatment
|
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.
|
Baseline to 30 days after the last dose of study treatment
|
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.
|
Baseline to 30 days after the last dose of study treatment
|
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.
|
Baseline to 30 days after the last dose of study treatment
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Nashat Y Gabrail, MD, Gabrail Cancer Center Research
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 26, 2021
Primary Completion (Anticipated)
April 1, 2024
Study Completion (Anticipated)
June 1, 2025
Study Registration Dates
First Submitted
April 8, 2021
First Submitted That Met QC Criteria
April 11, 2021
First Posted (Actual)
April 13, 2021
Study Record Updates
Last Update Posted (Actual)
September 8, 2022
Last Update Submitted That Met QC Criteria
September 6, 2022
Last Verified
September 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- MRG004A-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Advanced or Metastatic Solid Tumors
-
Suzhou Kanova Biopharmaceutical Co., LTDNot yet recruitingAdvanced or Metastatic Solid Tumors
-
Parthenon Therapeutics, Inc.RecruitingAdvanced or Metastatic Solid TumorsUnited States
-
PharmAbcineMerck Sharp & Dohme LLC; Novotech (Australia) Pty LimitedNot yet recruitingAdvanced or Metastatic Solid TumorsAustralia
-
Jiangsu Simcere Pharmaceutical Co., Ltd.Completed
-
Taiho Oncology, Inc.TerminatedAdvanced or Metastatic Solid Tumors Irrespective of Gene Alterations | Advanced or Metastatic Solid Tumors With Germline PTEN Inactivating MutationsUnited States, United Kingdom, Austria, France
-
DynamiCure BiotechnologyRecruitingAdvanced or Metastatic Solid TumorsUnited States, Australia
-
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.RecruitingAdvanced or Metastatic Solid TumorsChina
-
Shanghai Henlius BiotechActive, not recruitingAdvanced or Metastatic Solid TumorsAustralia
-
TakedaTakeda Development Center Americas, Inc.Active, not recruitingAdvanced or Metastatic Solid TumorsUnited States, China, Croatia, Japan, Latvia, Poland, Brazil, Lithuania, Switzerland
-
Ono Pharmaceutical Co. LtdActive, not recruitingAdvanced or Metastatic Solid TumorsJapan