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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
129
Administrated intravenously
University of California Irvine Chao Family Comprehensive Cancer Center
Orange, California, United States
MD Anderson Cancer Center
Houston, Texas, United States
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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: After signing informed consent until 45 days after the last dose of MRG002
Duration of Response (DoR)
Sensitivity analyses of DoR from the Investigator's assessment will be performed in the final analysis.
Time frame: Baseline to study completion (24 months)
Disease Control Rate (DCR)
Sensitivity analyses of DCR from the Investigator's assessment will be performed in the final analysis.
Time frame: Baseline to study completion (24 months)
Progression Free Survival (PFS)
Sensitivity analyses of PFS from the Investigator's assessment will be performed in the final analysis.
Time frame: Baseline to study completion (24 months)
Pharmacokinetics (PK) parameter for MRG002: Maximum Drug Concentration (Cmax)
Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics.
Time frame: Baseline to study completion (24 months)
PK parameter for MRG002: Area Under the Curve Up to the Last Validated Measurable Plasma Concentration (AUClast)
AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statistics.
Time frame: Baseline to study completion (24 months)
PK parameter for total antibody (TAb): Cmax
Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics.
Time frame: Baseline to study completion (24 months)
PK parameter for TAb: AUClast
AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statistics.
Time frame: Baseline to study completion (24 months)
PK parameter for Monomethyl Auristatin E (MMAE): Cmax
Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics.
Time frame: Baseline to study completion (24 months)
PK parameter for MMAE: AUClast
AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statistics.
Time frame: Baseline to study completion (24 months)
Immunogenicity
5 mL Blood samples for anti-drug antibody (ADA) analysis will be collected each time according to the pre-defined timepoints. The incidence of ADA will be summarized for all patients who received at least one administration of MRG002.
Time frame: Baseline to study completion (24 months)
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