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Safety Study of MGAH22 in HER2-positive Carcinomas

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ClinicalTrials.gov Identifier: NCT01148849
Recruitment Status : Active, not recruiting
First Posted : June 22, 2010
Last Update Posted : February 24, 2021
Sponsor:
Collaborators:
Green Cross Corporation
National Cancer Institute (NCI)
Information provided by (Responsible Party):
MacroGenics

Tracking Information
First Submitted Date  ICMJE June 17, 2010
First Posted Date  ICMJE June 22, 2010
Last Update Posted Date February 24, 2021
Study Start Date  ICMJE July 2010
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 21, 2010)
Occurrence of Adverse Events and Serious Adverse Events [ Time Frame: Study Day 50 or 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 21, 2010)
Maximum tolerated dose [ Time Frame: Study day 50 or 28 days after last infusion ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety Study of MGAH22 in HER2-positive Carcinomas
Official Title  ICMJE 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
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.
Detailed Description

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. Patients who have responded and received at least 3 years of MGAH22 study therapy may continue MGAH22 post-progression, with or without chemotherapy, at the Investigators' discretion.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Breast Cancer
  • Gastric Cancer
Intervention  ICMJE Biological: MGAH22

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 24 patients with breast or gastric cancer will be enrolled and treated at a dose of 15 mg/kg every three weeks.

Study Arms  ICMJE Experimental: MGAH22
Anti-HER2 monoclonal antibody (margetuximab)
Intervention: Biological: MGAH22
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 16, 2018)
66
Original Estimated Enrollment  ICMJE
 (submitted: June 21, 2010)
36
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Korea, Republic of,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01148849
Other Study ID Numbers  ICMJE CP-MGAH22-01
02598-10 ( Other Grant/Funding Number: NCI CRADA )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party MacroGenics
Study Sponsor  ICMJE MacroGenics
Collaborators  ICMJE
  • Green Cross Corporation
  • National Cancer Institute (NCI)
Investigators  ICMJE
Study Director: Fernanda Arnaldez, MD MacroGenics
PRS Account MacroGenics
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP