Safety Study of MGA271 in Refractory Cancer

February 4, 2022 updated by: MacroGenics

A Phase 1 Dose Escalation Study of MGA271 in Refractory Cancer

The purpose of this study is to evaluate the safety of MGA271 when given by intravenous (IV) infusion to patients with refractory cancer. The study will also evaluate how long MGA271 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 may have an effect on tumors.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

An open-label, multi-dose, single-arm, multi-center, Phase 1, dose-escalation study will be conducted to define the toxicity profile, maximum tolerated dose (MTD), pharmacokinetics (PK), immunogenicity, and potential antitumor activity of MGA271 in patients with refractory cancer that expresses B7-H3.

In the initial segments of the study, patients will be monitored for a minimum of four weeks after administration of the final dose of MGA271. Study assessments will include adverse event (AE) monitoring, electrocardiogram (ECG) monitoring, PK analysis of serum MGA271, determination of the serum concentration of soluble MGA271 and tumor markers, and an assessment of potential anti-MGA271 antibody [human anti-human antibody (HAHA)] response.

Tumor response assessments using Study Day 43 CT scans or MRI will be performed approximately six weeks after the first MGA271 dose for each patient. Patients with evidence of clinical benefit (partial or complete response or stable disease by RECIST or RANO Response criteria) will be allowed to continue therapy at the same dose, or at a reduced dose if warranted by dose limiting toxicity (DLT) or significant AE in Cycle 1. Subsequent cycles which will begin on Study Day 50 will consist of MGA271 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.

In the Expansion Segment of the study, patients will receive weekly, uninterrupted infusions with an initial response assessment at 8 weeks. Tumor evaluation will be carried out by both RECIST and immune-related response criteria (irRC).

Study Type

Interventional

Enrollment (Actual)

179

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA Hematology-Oncology Clinic
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale Cancer Center
    • Florida
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60637
        • The University of Chicago
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Norton Cancer Institute
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Cancer Center
      • Boston, Massachusetts, United States, 02111
        • Neely Center for Clinical Cancer Research, Tufts Medical Center
    • North Carolina
      • Huntersville, North Carolina, United States, 28078
        • Carolina Biooncology Institute
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania/Abramson Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed carcinoma (prostate cancer, renal cell carcinoma, head and neck cancer, triple-negative breast cancer, bladder cancer, non-small cell lung cancer) or melanoma that overexpresses B7-H3.
  • Progressive disease during or after last treatment regimen.
  • Appropriate treatment history for histological entity.
  • ECOG Performance Status <= 1.
  • Life expectancy >= 3 months.
  • Measurable disease or evaluable disease with relevant tumor marker elevation.
  • Acceptable laboratory parameters and adequate organ reserve.

Exclusion Criteria:

  • Major surgery or trauma within four weeks before enrollment.
  • Known hypersensitivity to murine or recombinant proteins, polysorbate 80, or any excipient contained in the drug formulation.
  • Grade 3 colitis, hepatitis, pneumonitis uveitis, myocarditis, myositis, CNS toxicity or autoimmune related neuromuscular toxicity such as myasthenia gravis associated with the administration of an immune checkpoint inhibitor
  • 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.
  • Vaccination within 2 weeks of enrollment (except for annual flu vaccine).
  • History of chronic or recurrent infections that require continual use of antiviral, antifungal, or antibacterial agents.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MGA271
Fc-optimized, humanized monoclonal antibody
Biological: MGA271

Up to 9 dose escalation cohorts will be enrolled to determine the maximum tolerated dose of MGA271. Patients with evidence of clinical benefit will be allowed to continue therapy at the same dose once per week for 3 weeks out of every 4-week cycle until documented progression.

Patients treated in the Expansion Segment at the maximum administered dose will receive weekly, uninterrupted infusions of MGA271 in 8 week cycles for up to 12 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety
Time Frame: Study Day 50 or 28 days after last infusion
Adverse events, serious adverse events, ECG monitoring, adrenal function monitoring, monitoring for development of anti-drug antibodies
Study Day 50 or 28 days after last infusion

Secondary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose
Time Frame: Study Day 50 or 28 days after last infusion
Study Day 50 or 28 days after last infusion

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tumor response
Time Frame: Every 8 weeks
Efficacy will be assessed every 8 weeks in the Expansion Segment according to immune-related response criteria
Every 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

MacroGenics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2011

Primary Completion (Actual)

April 18, 2019

Study Completion (Actual)

April 18, 2019

Study Registration Dates

First Submitted

July 7, 2011

First Submitted That Met QC Criteria

July 7, 2011

First Posted (Estimate)

July 11, 2011

Study Record Updates

Last Update Posted (Actual)

February 8, 2022

Last Update Submitted That Met QC Criteria

February 4, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CP-MGA271-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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