A Study of MRG002 in Patients with HER2-Positive Advanced Solid Tumors and Locally Advanced or Metastatic Gastric/Gastroesophageal Junction (GEJ) Cancer

Shanghai Miracogen

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Advanced Solid Tumors; Advanced or Metastatic Gastroesophageal Junction Cancer; Advanced or Metastatic Gastric Cancer

Treatments: Drug: MRG002

Study type: Interventional

Funder types: Industry

Identifiers

NCT04492488

MRG002-101

Details and patient eligibility

About

The objective of this study is to assess the safety, efficacy, and pharmacokinetics of MRG002, as well as the immunogenicity as defined by the incidence of anti-drug antibody (ADA) of MRG002 in patients with HER2-positive advanced solid tumors and locally advanced or metastatic gastric/gastroesophageal junction (GEJ) cancer.

Full description

This study consists of two parts. In Part A, patients will receive MRG002 as a monotherapy at doses of 2.2 or 2.6 mg/kg intravenously (IV) over 60-90 minute on Day 1 of every 3 weeks (Q3W), to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). In part B, patients will receive a single IV infusion of MRG002 at RP2D on Day 1 of Q3W.

Enrollment: 129 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• The patient must be able to provide written informed consent and follow the requirements specified in protocol.
• Age: ≥18 years.
• Life expectancy ≥6 months.
• Must have histologically or cytologically confirmed HER2-positive metastatic, unresectable cancer and must have had prior disease progression on all standard therapies for their tumor.
• Available archival tumor tissue (archival or from a new biopsy).
• At least one non-irradiated measurable tumor lesion according to RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Acceptable liver, renal, hematologic and coagulation function.

Exclusion criteria

• Toxicities (except alopecia & fatigue) due to prior antitumor therapy are higher than CTCAE v5.0 Grade 1.
• Toxicities due to radiotherapy (higher than grade 1) have not resolved to CTCAE v5.0 Grade ≤1 at least 21 days prior to the screening visit.
• Prior palliative or therapeutic radiation therapy to any RECIST v1.1 target lesion that defines baseline measurable disease for the study.
• Untreated or uncontrolled central nervous system (CNS) metastases.
• Any chemotherapy, biotherapy, immunotherapy, radiotherapy or other anti-tumor therapy within 3 weeks of the first dose of study treatment.
• Any severe cardiac dysfunction within 6 months of enrollment.
• 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 hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure > 100 mmHg).
• History of ventricular tachycardia, or torsade des pointes.
• History of moderate to severe dyspnea at rest due to advanced malignancies or their complications, severe primary lung disease, current need of continuous oxygen therapy, or clinically active interstitial lung disease (ILD) or pneumonitis.
• 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 MRG002 or known allergic reactions to trastuzumab or other prior anti-HER2 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.
• 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.
• Use of systemic corticosteroids within 4 weeks prior to the first dose of treatment.
• Use of strong CYP3A4 inhibitors.
• Pregnancy or breast-feeding.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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129 participants in 2 patient groups

Solid Tumors

Experimental group

Description:

Phase I Dose Escalation: MRG002 will be administrated by an IV infusion of escalating doses (starting dose of 2.2 mg/kg, followed by 2.6 mg/kg) on Day 1 of every 3 weeks (21-day cycle).

Treatment:

Drug: MRG002

Locally Advanced or Metastatic Gastric/GEJ Cancer

Experimental group

Description:

MRG002 will be administrated by an IV infusion on Day 1 of every 3 weeks (21-day cycle).

Treatment:

Drug: MRG002