Breast Cancer, Gastric Cancer
Conditions
Brief summary
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.
Interventions
BIOLOGICALmargetuximab
margetuximab
Sponsors
Green Cross Corporation
National Cancer Institute (NCI)
MacroGenics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Adverse Events and Serious Adverse Events | Up to 28 days after last infusion | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with dose limiting toxicities every 3-week dosing | Up to Study Day 21 day for every 3-week dosing | Characterize maximum tolerated dose (MTD) or maximum administered dose (MAD) (if no MTD is defined) of margetuximab |
| Concentration of Margetuximab at Steady State once-weekly doses of margetuximab | 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) | 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 | 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 | Study Day 1 through Day 22 | AUC is a mathematical calculation that describes the drug concentration in the blood over time. |
| Area Under the Concentration Time Curve at Steady State (AUC ss) weekly dosing schedule | Study Day 1 through Day 8 | AUC is a mathematical calculation that describes the drug concentration in the blood over time. |
| Clearance once every 3 weeks schedule | Study Day 1, 2, 4, 5, 22, 29 ,36, 50, every 3 weeks thereafter through study completion, average 10 months | Drug clearance is the amount of drug removed from the bloodstream per unit of time. |
| Volume of Distribution at Steady State once every 3 weeks | Study Day 1, 2, 4, 5, 22, 29 ,36, 50, every 3 weeks thereafter through study completion, average 10 months | The volume of distribution is related to a whether how much drug is distributed to body tissues or remains in the bloodstream |
| Terminal Half-life once every 3 weeks schedule | Study Day 1 through Day 22 | Terminal half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium. |
| Terminal Half-life once every weekly dosing schedule | Study Day 1 through Day 8 | Terminal half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium. |
| Number of participants with dose limiting toxicities for weekly dosing | up to Study Day 28 for weekly dosing | Characterize maximum tolerated dose (MTD) or maximum administered dose (MAD) (if no MTD is defined) of margetuximab |
| Number of Patients with a Complete Response (CR) or Partial Response (PR) to Treatment | Assessed at 6, 18, 30, 42, and 54 weeks, they every 24 weeks until treatment discontinuation, average 10 months | 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 |
| Duration of response | Assessed at 6, 18, 30, 42, and 54 weeks, they every 24 weeks until treatment discontinuation,average 10 months | Duration of response is calculated at the time from CR or PR to relapse or cancer progression |
| Progression free survival | Assessed at 6, 18, 30, 42, and 54 weeks, they every 24 weeks until treatment discontinuation, average 10 months | The interval between the first dose of study medication and progression of disease or death from any cause |
| Number of patients with complete response, partial response, stable disease, or progressive disease according to each CD16A-158 genotype (FF, FV, VV) | 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 | Fc Receptor polymorphisms may affect responsiveness to immunotherapies |
| Changes in immune cell subsets | Before infusion and 1 hour after infusion on Study Day 1, Study Day 2, before infusion on Study Day 22 and 50 | Changes in immune cell subsets may affect responsiveness to immunotherapies |
| Serum cytokines in the blood | Study Day 1, 2, 4, 5, 22, 29 ,36, 50, every 3 weeks thereafter through study completion, average 10 months | Changes in the levels of cytokines in the blood may be related to an immune response to treatment. |
| Amount HER2 in the blood | Before infusion and 1 hour after infusion on Study Day 1, Study Day 2, before infusion on Study Day 22 and 50 | Levels of HER2 in the bloodstream may indicate response to treatment. |
| Antibody dependent cellular cytotoxicity (ADCC) activity | Before infusion and 1 hour after infusion on Study Day 1, Study Day 2, before infusion on Study Day 22 and 50 | ADCC activity is the ability of immune cells (like lymphocytes) to kill cells that have immune markers (like HER2) on the cell surface |
| Fc receptor occupancy | 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 is the amount of time that the receptor is bound to an immune marker (like HER2) on the cell surface. |
| Number of Patients Who Develop Treatment-emergent Anti-drug Antibodies to Margetuximab once every 3 weeks schedule | Study Day 1, 2, 4, 5, 22, 29 ,36, 50, every 3 weeks thereafter through study completion, average 10 months | — |
Countries
South Korea, United States
Outcome results
None listed