Clinical trial NCT01148849: Safety Study of MGAH22 in HER2-positive Carcinomas
Official title: A Phase 1, Dose Escalation Study of MGAH22 in Patients With Refractory HER2 Positive Breast Cancer and Patients With Other HER2 Positive Carcinomas for Whom No Standard Therapy Is Available
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Gastric Cancer
Lead sponsor: MacroGenics
Sponsor class: INDUSTRY
Collaborators: name: Green Cross Corporation
name: National Cancer Institute (NCI)
First posted: 2010-06-22
Enrollment: 66
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 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Occurrence of Adverse Events and Serious Adverse Events
timeFrame: Up to 28 days after last infusion
Secondary outcomes:
measure: Number of participants with dose limiting toxicities for weekly dosing
timeFrame: up to Study Day 28 for weekly dosing
measure: Number of participants with dose limiting toxicities every 3-week dosing
timeFrame: Up to Study Day 21 day for every 3-week dosing
measure: Concentration of Margetuximab at Steady State once-weekly doses of margetuximab
timeFrame: Study Day 1, 2, 4, 5, 8, 15, 22, 29 ,36, 50, every 4 weeks thereafter throughout study completion, average 2 months.
measure: Number of patients who develop treatment-emergent anti-drug antibodies to margetuximab (Immunogenicity)
timeFrame: Study Day 1, 22, 50, every 4 weeks thereafter throughout study completion, average 2 months.
measure: Maximum Concentration of Margetuximab at Steady State once every 3 weeks schedule
timeFrame: Study Day 1, 2, 4, 5, 22, 29 ,36, 50, every 3 weeks thereafter throughout study completion, average 10 months.
measure: Area Under the Concentration Time Curve at Steady State (AUC ss) once every 3 weeks schedule
timeFrame: Study Day 1 through Day 22
measure: Area Under the Concentration Time Curve at Steady State (AUC ss) weekly dosing schedule
timeFrame: Study Day 1 through Day 8
measure: Clearance once every 3 weeks schedule
timeFrame: Study Day 1, 2, 4, 5, 22, 29 ,36, 50, every 3 weeks thereafter through study completion, average 10 months
measure: Volume of Distribution at Steady State once every 3 weeks
timeFrame: Study Day 1, 2, 4, 5, 22, 29 ,36, 50, every 3 weeks thereafter through study completion, average 10 months
measure: Terminal Half-life once every 3 weeks schedule
timeFrame: Study Day 1 through Day 22
measure: Terminal Half-life once every weekly dosing schedule
timeFrame: Study Day 1 through Day 8
measure: Number of Patients Who Develop Treatment-emergent Anti-drug Antibodies to Margetuximab once every 3 weeks schedule
timeFrame: Study Day 1, 2, 4, 5, 22, 29 ,36, 50, every 3 weeks thereafter through study completion, average 10 months
measure: Number of Patients with a Complete Response (CR) or Partial Response (PR) to Treatment
timeFrame: Assessed at 6, 18, 30, 42, and 54 weeks, they every 24 weeks until treatment discontinuation, average 10 months
measure: Duration of response
timeFrame: Assessed at 6, 18, 30, 42, and 54 weeks, they every 24 weeks until treatment discontinuation,average 10 months
measure: Progression free survival
timeFrame: Assessed at 6, 18, 30, 42, and 54 weeks, they every 24 weeks until treatment discontinuation, average 10 months
measure: Number of patients with complete response, partial response, stable disease, or progressive disease according to each CD16A-158 genotype (FF, FV, VV)
timeFrame: 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
measure: Changes in immune cell subsets
timeFrame: Before infusion and 1 hour after infusion on Study Day 1, Study Day 2, before infusion on Study Day 22 and 50
measure: Serum cytokines in the blood
timeFrame: Study Day 1, 2, 4, 5, 22, 29 ,36, 50, every 3 weeks thereafter through study completion, average 10 months
measure: Amount HER2 in the blood
timeFrame: Before infusion and 1 hour after infusion on Study Day 1, Study Day 2, before infusion on Study Day 22 and 50
measure: Antibody dependent cellular cytotoxicity (ADCC) activity
timeFrame: Before infusion and 1 hour after infusion on Study Day 1, Study Day 2, before infusion on Study Day 22 and 50
measure: Fc receptor occupancy
timeFrame: Before infusion and 1 hour after infusion on Study Day 1, Study Day 2, before infusion on Study Day 22 and 50
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Cancer Institute
state: Maryland
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
References:
citation: Bang YJ, Giaccone G, Im SA, Oh DY, Bauer TM, Nordstrom JL, Li H, Chichili GR, Moore PA, Hong S, Stewart SJ, Baughman JE, Lechleider RJ, Burris HA. First-in-human phase 1 study of margetuximab (MGAH22), an Fc-modified chimeric monoclonal antibody, in patients with HER2-positive advanced solid tumors. Ann Oncol. 2017 Apr 1;28(4):855-861. doi: 10.1093/annonc/mdx002.