Description:
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.
Title
- Brief Title: Safety Study of MGA271 in Refractory Cancer
- Official Title: A Phase 1 Dose Escalation Study of MGA271 in Refractory Cancer
Clinical Trial IDs
- ORG STUDY ID:
CP-MGA271-01
- NCT ID:
NCT01391143
Conditions
- Prostate Cancer
- Melanoma
- Renal Cell Carcinoma
- Triple-negative Breast Cancer
- Head and Neck Cancer
- Bladder Cancer
- Non-small Cell Lung Cancer
Interventions
| Drug | Synonyms | Arms |
|---|
| MGA271 | | MGA271 |
Purpose
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).
Trial Arms
| Name | Type | Description | Interventions |
|---|
| MGA271 | Experimental | Fc-optimized, humanized monoclonal antibody | |
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Safety |
| Time Frame: | Study Day 50 or 28 days after last infusion |
| Safety Issue: | |
| Description: | Adverse events, serious adverse events, ECG monitoring, adrenal function monitoring, monitoring for development of anti-drug antibodies |
Secondary Outcome Measures
| Measure: | Maximum tolerated dose |
| Time Frame: | Study Day 50 or 28 days after last infusion |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | MacroGenics |
Trial 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
Last Updated
January 10, 2020
