Safety Study of MGAH22 in HER2-positive Carcinomas

MacroGenics66 enrolled

Overview

The purpose of this study is to determine if MGAH22 is safe when given by intravenous (IV) infusion to patients with HER2-positive cancer. The study will also evaluate how long MGAH22 stays in the blood and how long it takes for it to leave the body, what is the highest dose that can safely be given, and whether it has an effect on tumors.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Breast Cancer Gastric Cancer

Interventions

margetuximabBIOLOGICAL

margetuximab

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histologically or cytologically confirmed carcinoma that overexpresses HER2 by immunohistochemistry (2+ or 3+ positivity by HercepTest or equivalent). * Progressive disease during or after last treatment regimen. * Appropriate treatment history for histological entity. * ECOG Performance Status \<= 1. * Life expectancy \>= 3 month. * Measurable disease * Acceptable laboratory parameters and adequate organ reserve. * Baseline LVEF \>50% Exclusion Criteria: * Lifetime anthracycline exposure \> 350 mg/m2 of doxorubicin or equivalent * Major surgery within four weeks before enrollment. * Known hypersensitivity to murine or recombinant proteins, polysorbate 80, or any excipient contained in the drug formulation. * Second primary malignancy that has not been in remission for greater than 3 years. Treated non-melanoma skin cancer, cervical carcinoma in situ on biopsy, or squamous intraepithelial lesion on PAP smear, localized prostate cancer (Gleason score \< 6), or resected melanoma in situ are exceptions and do not require a 3 year remission. * Active viral, bacterial, or systemic fungal infection requiring parenteral treatment within four weeks of enrollment. Patients requiring any oral antiviral, fungal, or bacterial therapy must have completed treatment within one week of enrollment. * History of chronic or recurrent infections that require continual use of antiviral, antifungal, or antibacterial agents. * History of deep vein thrombosis, pulmonary embolism, myocardial infarction, or stroke within three months of enrollment. * Known history of central nervous system (CNS) metastatic disease with evidence of residual or recurrent disease upon entry. * New York Heart Association class III or IV heart disease.

Locations (3)

National Cancer Institute

Bethesda, Maryland, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Seoul National University Hospital

Seoul, South Korea

Outcomes

Primary Outcomes

Occurrence of Adverse Events and Serious Adverse Events

Note that serious adverse events that are considered study drug related can be reported at any time after Study Day 50 or 28 days after the last infusion.

Time frame: Up to 28 days after last infusion

Secondary Outcomes

Number of participants with dose limiting toxicities for weekly dosing

Characterize maximum tolerated dose (MTD) or maximum administered dose (MAD) (if no MTD is defined) of margetuximab

Time frame: up to Study Day 28 for weekly dosing

Number of participants with dose limiting toxicities every 3-week dosing

Characterize maximum tolerated dose (MTD) or maximum administered dose (MAD) (if no MTD is defined) of margetuximab

Time frame: Up to Study Day 21 day for every 3-week dosing

Concentration of Margetuximab at Steady State once-weekly doses of margetuximab

Time frame: Study Day 1, 2, 4, 5, 8, 15, 22, 29 ,36, 50, every 4 weeks thereafter throughout study completion, average 2 months.

Number of patients who develop treatment-emergent anti-drug antibodies to margetuximab (Immunogenicity)

Time frame: Study Day 1, 22, 50, every 4 weeks thereafter throughout study completion, average 2 months.

Maximum Concentration of Margetuximab at Steady State once every 3 weeks schedule

Time frame: Study Day 1, 2, 4, 5, 22, 29 ,36, 50, every 3 weeks thereafter throughout study completion, average 10 months.

Area Under the Concentration Time Curve at Steady State (AUC ss) once every 3 weeks schedule

AUC is a mathematical calculation that describes the drug concentration in the blood over time.

Data from ClinicalTrials.gov

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Time frame: Study Day 1 through Day 22

Area Under the Concentration Time Curve at Steady State (AUC ss) weekly dosing schedule

AUC is a mathematical calculation that describes the drug concentration in the blood over time.

Time frame: Study Day 1 through Day 8

Clearance once every 3 weeks schedule

Drug clearance is the amount of drug removed from the bloodstream per unit of time.

Time frame: Study Day 1, 2, 4, 5, 22, 29 ,36, 50, every 3 weeks thereafter through study completion, average 10 months

Volume of Distribution at Steady State once every 3 weeks

The volume of distribution is related to a whether how much drug is distributed to body tissues or remains in the bloodstream

Time frame: Study Day 1, 2, 4, 5, 22, 29 ,36, 50, every 3 weeks thereafter through study completion, average 10 months

Terminal Half-life once every 3 weeks schedule

Terminal half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium.

Time frame: Study Day 1 through Day 22

Terminal Half-life once every weekly dosing schedule

Terminal half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium.

Time frame: Study Day 1 through Day 8

Number of Patients Who Develop Treatment-emergent Anti-drug Antibodies to Margetuximab once every 3 weeks schedule

Time frame: Study Day 1, 2, 4, 5, 22, 29 ,36, 50, every 3 weeks thereafter through study completion, average 10 months

Number of Patients with a Complete Response (CR) or Partial Response (PR) to Treatment

Investigate the preliminary anti-tumor activity as measured by response to treatment of margetuximab, using conventional Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Time frame: Assessed at 6, 18, 30, 42, and 54 weeks, they every 24 weeks until treatment discontinuation, average 10 months

Duration of response

Duration of response is calculated at the time from CR or PR to relapse or cancer progression

Time frame: Assessed at 6, 18, 30, 42, and 54 weeks, they every 24 weeks until treatment discontinuation,average 10 months

Progression free survival

The interval between the first dose of study medication and progression of disease or death from any cause

Time frame: Assessed at 6, 18, 30, 42, and 54 weeks, they every 24 weeks until treatment discontinuation, average 10 months

Number of patients with complete response, partial response, stable disease, or progressive disease according to each CD16A-158 genotype (FF, FV, VV)

Fc Receptor polymorphisms may affect responsiveness to immunotherapies

Time frame: Fc receptor genotypes assessed prior to study treatment. Response to treatment assessed at 6, 18, 30, 42, and 54 weeks, then every 24 weeks until treatment discontinuation, average 10 months

Changes in immune cell subsets

Changes in immune cell subsets may affect responsiveness to immunotherapies

Time frame: Before infusion and 1 hour after infusion on Study Day 1, Study Day 2, before infusion on Study Day 22 and 50

Serum cytokines in the blood

Changes in the levels of cytokines in the blood may be related to an immune response to treatment.

Time frame: Study Day 1, 2, 4, 5, 22, 29 ,36, 50, every 3 weeks thereafter through study completion, average 10 months

Amount HER2 in the blood

Levels of HER2 in the bloodstream may indicate response to treatment.

Time frame: Before infusion and 1 hour after infusion on Study Day 1, Study Day 2, before infusion on Study Day 22 and 50

Antibody dependent cellular cytotoxicity (ADCC) activity

ADCC activity is the ability of immune cells (like lymphocytes) to kill cells that have immune markers (like HER2) on the cell surface

Time frame: Before infusion and 1 hour after infusion on Study Day 1, Study Day 2, before infusion on Study Day 22 and 50

Fc receptor occupancy

Fc receptor occupancy is the amount of time that the receptor is bound to an immune marker (like HER2) on the cell surface.

Time frame: Before infusion and 1 hour after infusion on Study Day 1, Study Day 2, before infusion on Study Day 22 and 50