Safety Study of MGAH22 in HER2-positive Carcinomas
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- Occurrence of Adverse Events and Serious Adverse Events [ Time Frame: Study Day 50 or 28 days after last infusion ] [ Designated as safety issue: Yes ]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.
- Maximum tolerated dose [ Time Frame: Study day 50 or 28 days after last infusion ] [ Designated as safety issue: Yes ]
|Study Start Date:||July 2010|
|Estimated Study Completion Date:||March 2016|
|Estimated Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
Anti-HER2 monoclonal antibody
MGAH22 will be administered by IV infusion once per week for 4 weeks in the following dose escalation cohorts: 0.1, 0.3, 1.0, 3.0, and 6.0 mg/kg; and once every 3 weeks in the following dose escalation cohorts: 10.0, 15.0, and 18.0 mg/kg.
An additional cohort of up to 15 patients with breast or gastric cancer will be enrolled and treated at a dose of 15 mg/kg every three weeks.
An open-label, multi-dose, single-arm, multi-center, Phase 1, dose-escalation study will be conducted to define the toxicity profile, MTD, PK, immunogenicity, and potential antitumor activity of MGAH22 in patients with refractory HER2 positive breast cancer and patients with other carcinomas that overexpress HER2 for whom no standard therapy is available. After an MTD has been defined, an additional cohort of patients will be treated at the MTD to obtain further information regarding the safety of the chosen dose, to definitively describe PK, and to evaluate potential anti-tumor activity of MGAH22.
Patients will be monitored for a minimum of four weeks after administration of the final dose of MGAH22. The National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events (CTCAE), v.4.0, will be used for grading AEs except as noted within the protocol. Study assessments will include AE monitoring, ECG monitoring, PK analysis of serum MGAH22, determination of the serum concentration of soluble MGAH22 and tumor markers, and an assessment of potential anti-MGAH22 antibody [human anti-chimeric antibody (HACA)] response.
Tumor response assessments using Study Day 43 CT scans will be performed approximately six weeks after the first MGAH22 dose for each patient. Patients with evidence of disease regression (partial or complete response or stable disease by RECIST criteria) will be allowed to continue therapy at the same dose, or at a reduced dose if warranted by DLT or significant AE in Cycle 1. Subsequent cycles which will begin on Study Day 50 will consist of MGAH22 administration on Study Days 1, 8, and 15 of each 28-day cycle, with tumor evaluation every other cycle. Responding patients may receive continued antibody therapy until evidence of progression of disease is documented or the patient experiences DLT.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01148849
|United States, Maryland|
|National Cancer Institute|
|Bethesda, Maryland, United States, 20892|
|United States, Tennessee|
|Sarah Cannon Research Institute|
|Nashville, Tennessee, United States, 37203|
|Korea, Republic of|
|Seoul National University Hospital|
|Seoul, Korea, Republic of, 110-744|
|Study Director:||Robert Lechleider, MD||MacroGenics|