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).
- 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.
- 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.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both