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

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.

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.