Safety Study of MGA271 in Refractory Cancer

Prostate Cancer Clinical Trial

Official title:

A Phase 1 Dose Escalation Study of MGA271 in Refractory Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01391143
• Other study ID #: CP-MGA271-01
• Status: Completed
• Phase: Phase 1
• Start date: July 2011
• Est. completion date: April 18, 2019

Study information

• Verified date: February 2022
• Source: MacroGenics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 179
• Est. completion date: April 18, 2019
• Est. primary completion date: April 18, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bladder Cancer
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Renal Cell
• Head and Neck Cancer
• Head and Neck Neoplasms
• Melanoma
• Non-small Cell Lung Cancer
• Prostate Cancer
• Prostatic Neoplasms
• Renal Cell Carcinoma
• Triple Negative Breast Neoplasms
• Triple-negative Breast Cancer
• Urinary Bladder Neoplasms

Intervention

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.

Locations

Country	Name	City	State
United States	University of Maryland	Baltimore	Maryland
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Neely Center for Clinical Cancer Research, Tufts Medical Center	Boston	Massachusetts
United States	The University of Chicago	Chicago	Illinois
United States	Carolina Biooncology Institute	Huntersville	North Carolina
United States	UCLA Hematology-Oncology Clinic	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	Hospital of the University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
MacroGenics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Tumor response	Efficacy will be assessed every 8 weeks in the Expansion Segment according to immune-related response criteria	Every 8 weeks
Primary	Safety	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	Maximum tolerated dose		Study Day 50 or 28 days after last infusion