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

NCT04492488 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: MRG002-101
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

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

Keywords

MRG002; Antibody Drug Conjugate (ADC); HER2; Solid tumors; Gastric/GEJ Cancer

Outcome Measures

Primary Outcomes (4)

• Maximum Tolerated Dose (MTD)

  The dose level in which (i) less than 2 out of 6 patients in a treatment cohort experiences dose-limiting toxicity (DLT); or (ii) \<33% of an evaluable patient treatment cohort experiences DLT.

  DLT will be evaluated during the first 21-day treatment cycle (Cycle 1)

• Recommended Phase II Dose (RP2D)

  Identify the recommended Phase II dose (RP2D) of MRG002 for Phase II clinical study. The RP2D may be the same as the MTD or an evaluable dose level lower than the MTD.

  Day 1 to Day 21 of Cycle 1

• Objective Response Rate (ORR)

  Objective response rate (ORR) will be assessed by Independent Central Review (ICR) based on RECIST v1.1. Cumulative safety and dosing data will be reviewed by an independent Data Safety Monitoring Board (DSMB).

  Baseline to study completion (24 months)

• Incidence of Adverse Events (AEs)

  AEs will be coded using MedDAR. Descriptive statistics will be used to summarize results to assess the safety and tolerability profile of MRG002.

  After signing informed consent until 45 days after the last dose of MRG002

Secondary Outcomes (10)

• Duration of Response (DoR)

  Baseline to study completion (24 months)

• Disease Control Rate (DCR)

  Baseline to study completion (24 months)

• Progression Free Survival (PFS)

  Baseline to study completion (24 months)

• Pharmacokinetics (PK) parameter for MRG002: Maximum Drug Concentration (Cmax)

  Baseline to study completion (24 months)

• PK parameter for MRG002: Area Under the Curve Up to the Last Validated Measurable Plasma Concentration (AUClast)

  Baseline to study completion (24 months)

Study Arms (2)

Solid Tumors

EXPERIMENTAL

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).

Drug: MRG002

Locally Advanced or Metastatic Gastric/GEJ Cancer

EXPERIMENTAL

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

Drug: MRG002

Interventions

MRG002 DRUG

Administrated intravenously

Locally Advanced or Metastatic Gastric/GEJ Cancer; Solid Tumors

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai Miracogen Inc.: lead

Study Sites (2)

University of California Irvine Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77040, United States

Location

MeSH Terms

Conditions

Stomach Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Officials

• Crystal Denlinger, MD

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2020
• First Posted: July 30, 2020
• Study Start: May 24, 2021
• Primary Completion: October 18, 2022
• Study Completion: December 31, 2024
• Last Updated: October 22, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)