Clinical trial NCT04843709: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Advanced or Metastatic Solid Tumors
Keywords: MRG004A
Antibody drug conjugate (ADC)
Tissue factor
Solid tumors
Lead sponsor: Shanghai Miracogen Inc.
Sponsor class: INDUSTRY
First posted: 2021-04-13
Enrollment: 181
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: DLT will be evaluated during the first treatment cycle (Day 1-21)
measure: Recommended Phase II Dose (RP2D)
timeFrame: Baseline to study completion (up to 24 months)
measure: Objective Response Rate (ORR)
timeFrame: Baseline to study completion (up to 24 months)
measure: Adverse Events (AEs)
timeFrame: From signing informed consent until 45 days after the last dose of MRG004A
Secondary outcomes:
measure: Duration of Response (DoR)
timeFrame: Baseline to study completion (up to 24 months)
measure: Disease Control Rate (DCR)
timeFrame: Baseline to study completion (up to 24 months)
measure: Progression Free Survival (PFS)
timeFrame: Baseline to study completion (up to 24 months)
measure: Overall Survive (OS)
timeFrame: Baseline to study completion (up to 24 months)
measure: Pharmacokinetics (PK) Parameter of MRG004A: Cmax
timeFrame: Baseline to 30 days after the last dose of study treatment
measure: Pharmacokinetics (PK) Parameter of MRG004A: Tmax
timeFrame: Baseline to 30 days after the last dose of study treatment
measure: Pharmacokinetics (PK) Parameter of MRG004A: AUClast
timeFrame: Baseline to 30 days after the last dose of study treatment
measure: Incidence of anti-drug antibody (ADA)
timeFrame: Baseline to 30 days after the last dose of study treatment
Other outcomes:
Locations:
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center
state: California
city: New York
country: United States
facility: Memorial Sloan Kettering 60th Street Outpatient Center
state: New York
city: Canton
country: United States
facility: Gabrail Cancer Center Research
state: Ohio
city: Cincinnati
country: United States
facility: The Christ Hospital Cancer Center
state: Ohio
city: Gettysburg
country: United States
facility: Gettysburg Cancer Center
state: Pennsylvania
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Hangzhou
country: China
facility: The First Affiliated Hospital, College of Medicine, Zhejiang University
state: Zhejiang
Study officials:
affiliation: Gabrail Cancer Center Research
name: Nashat Y Gabrail, MD
role: PRINCIPAL_INVESTIGATOR
References: