Clinical trial NCT01391143: Safety Study of MGA271 in Refractory Cancer
Official title: A Phase 1 Dose Escalation Study of MGA271 in Refractory Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: MacroGenics
Sponsor class: INDUSTRY
First posted: 2011-07-11
Enrollment: 179
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Safety
timeFrame: Study Day 50 or 28 days after last infusion
Secondary outcomes:
measure: Maximum tolerated dose
timeFrame: Study Day 50 or 28 days after last infusion
Other outcomes:
measure: Tumor response
timeFrame: Every 8 weeks
Locations:
city: Los Angeles
country: United States
facility: UCLA Hematology-Oncology Clinic
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Neely Center for Clinical Cancer Research, Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Huntersville
country: United States
facility: Carolina Biooncology Institute
state: North Carolina
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania/Abramson Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
Study officials:
affiliation: MacroGenics
name: Chief Medical Officer
role: STUDY_DIRECTOR
References: