Clinical trial NCT04492488: A Study of MRG002 in Patients with HER2-Positive Advanced Solid Tumors and Locally Advanced or Metastatic Gastric/Gastroesophageal Junction (GEJ) Cancer
Official title: An Open-Label, Multi-center Phase I/II Dose Escalation and Expansion Study to Assess the Safety, Efficacy and Pharmacokinetics of MRG002 in Patients with HER2-Positive Advanced Solid Tumors and Locally Advanced or Metastatic Gastric/Gastroesophageal Junction (GEJ) Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
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
Lead sponsor: Shanghai Miracogen Inc.
Sponsor class: INDUSTRY
First posted: 2020-07-30
Enrollment: 129
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: DLT will be evaluated during the first 21-day treatment cycle (Cycle 1)
measure: Recommended Phase II Dose (RP2D)
timeFrame: Day 1 to Day 21 of Cycle 1
measure: Objective Response Rate (ORR)
timeFrame: Baseline to study completion (24 months)
measure: Incidence of Adverse Events (AEs)
timeFrame: After signing informed consent until 45 days after the last dose of MRG002
Secondary outcomes:
measure: Duration of Response (DoR)
timeFrame: Baseline to study completion (24 months)
measure: Disease Control Rate (DCR)
timeFrame: Baseline to study completion (24 months)
measure: Progression Free Survival (PFS)
timeFrame: Baseline to study completion (24 months)
measure: Pharmacokinetics (PK) parameter for MRG002: Maximum Drug Concentration (Cmax)
timeFrame: Baseline to study completion (24 months)
measure: PK parameter for MRG002: Area Under the Curve Up to the Last Validated Measurable Plasma Concentration (AUClast)
timeFrame: Baseline to study completion (24 months)
measure: PK parameter for total antibody (TAb): Cmax
timeFrame: Baseline to study completion (24 months)
measure: PK parameter for TAb: AUClast
timeFrame: Baseline to study completion (24 months)
measure: PK parameter for Monomethyl Auristatin E (MMAE): Cmax
timeFrame: Baseline to study completion (24 months)
measure: PK parameter for MMAE: AUClast
timeFrame: Baseline to study completion (24 months)
measure: Immunogenicity
timeFrame: Baseline to study completion (24 months)
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California Irvine Chao Family Comprehensive Cancer Center
state: California
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Fox Chase Cancer Center
name: Crystal Denlinger, MD
role: PRINCIPAL_INVESTIGATOR
References: