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Safety Study of MGA271 in Refractory Cancer

Primary Purpose

Prostate Cancer, Melanoma, Renal Cell Carcinoma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

MGA271

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring Prostate cancer, Melanoma, Renal cell carcinoma, Triple-negative breast cancer, Head and neck cancer, Bladder cancer, Non-small cell lung cancer, Squamous cell carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

UCLA Hematology-Oncology Clinic
Yale Cancer Center
Moffitt Cancer Center
The University of Chicago
Norton Cancer Institute
University of Maryland
Neely Center for Clinical Cancer Research, Tufts Medical Center
Massachusetts General Hospital Cancer Center
Dana Farber Cancer Institute
Carolina Biooncology Institute
Hospital of the University of Pennsylvania/Abramson Cancer Center
Sarah Cannon Research Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

MGA271

Arm Description

Fc-optimized, humanized monoclonal antibody

Outcomes

Primary Outcome Measures

Safety

Adverse events, serious adverse events, ECG monitoring, adrenal function monitoring, monitoring for development of anti-drug antibodies

Secondary Outcome Measures

Maximum tolerated dose

Full Information

NCT ID

NCT01391143

First Posted

July 7, 2011

Last Updated

February 4, 2022

Sponsor

MacroGenics

1. Study Identification

Unique Protocol Identification Number

NCT01391143

Brief Title

Safety Study of MGA271 in Refractory Cancer

Official Title

A Phase 1 Dose Escalation Study of MGA271 in Refractory Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

February 2022

Overall Recruitment Status

Completed

Study Start Date

July 2011 (undefined)

Primary Completion Date

April 18, 2019 (Actual)

Study Completion Date

April 18, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

MacroGenics

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Cancer, Melanoma, Renal Cell Carcinoma, Triple-negative Breast Cancer, Head and Neck Cancer, Bladder Cancer, Non-small Cell Lung Cancer

Keywords

Prostate cancer, Melanoma, Renal cell carcinoma, Triple-negative breast cancer, Head and neck cancer, Bladder cancer, Non-small cell lung cancer, Squamous cell carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

179 (Actual)

8. Arms, Groups, and Interventions

Arm Title

MGA271

Arm Type

Experimental

Arm Description

Fc-optimized, humanized monoclonal antibody

Intervention Type

Biological

Intervention Name(s)

MGA271

Intervention Description

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.

Primary Outcome Measure Information:

Title

Safety

Description

Adverse events, serious adverse events, ECG monitoring, adrenal function monitoring, monitoring for development of anti-drug antibodies

Time Frame

Study Day 50 or 28 days after last infusion

Secondary Outcome Measure Information:

Title

Maximum tolerated dose

Time Frame

Study Day 50 or 28 days after last infusion

Other Pre-specified Outcome Measures:

Title

Tumor response

Description

Efficacy will be assessed every 8 weeks in the Expansion Segment according to immune-related response criteria

Time Frame

Every 8 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Chief Medical Officer

Organizational Affiliation

MacroGenics

Official's Role

Study Director

Facility Information:

Facility Name

UCLA Hematology-Oncology Clinic

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

Yale Cancer Center

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06520

Country

United States

Facility Name

Moffitt Cancer Center

City

Tampa

State/Province

Florida

ZIP/Postal Code

33612

Country

United States

Facility Name

The University of Chicago

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

Facility Name

Norton Cancer Institute

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40202

Country

United States

Facility Name

University of Maryland

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21201

Country

United States

Facility Name

Neely Center for Clinical Cancer Research, Tufts Medical Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02111

Country

United States

Facility Name

Massachusetts General Hospital Cancer Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Dana Farber Cancer Institute

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Facility Name

Carolina Biooncology Institute

City

Huntersville

State/Province

North Carolina

ZIP/Postal Code

28078

Country

United States

Facility Name

Hospital of the University of Pennsylvania/Abramson Cancer Center

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

Sarah Cannon Research Institute

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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Safety Study of MGA271 in Refractory Cancer

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